Friederike Körber - Academia.edu (original) (raw)

Papers by Friederike Körber

Research paper thumbnail of Referenz Endokrinologie und Diabetologie

Referenz Endokrinologie und Diabetologie, 2020

Research paper thumbnail of Nierenbeckenkelchsystemerweiterung und eine flüssigkeitsgefüllte Blase im Unterbauch

Monatsschrift Kinderheilkunde

Research paper thumbnail of Segmentale arterielle Mediolyse bei einem Neugeborenen mit Plazentabeteiligung

Zeitschrift für Geburtshilfe und Neonatologie, 2004

Research paper thumbnail of True thymic hyperplasia associated with severe thymic cyst bleeding in a newborn: case report and review of the literature

Annals of Diagnostic Pathology, 2007

We report on a 5-week-old male infant with recurrent respiratory distress since birth and congeni... more We report on a 5-week-old male infant with recurrent respiratory distress since birth and congenital thymic hyperplasia. Acute life-threatening thymic bleeding apparently from ruptured thymic cysts into the pleural spaces complicated the clinical situation. Thoracotomy and complete thymectomy were performed. Histologic examination revealed normal thymic architecture with cysts of different sizes and an increased thymic weight of 30 g. The combination of true thymic hyperplasia and cyst bleeding in a newborn has not been previously reported and will be discussed in relation to the available literature on respiratory distress due to thymic pathology in childhood.

Research paper thumbnail of Einfluss von intranasal verabreichter Muttermilch bei Frühgeborenen mit hochgradigen intraventrikulären Blutungen – erste sonografische Ergebnisse

RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2017

Research paper thumbnail of Standardisierte Durchführung der Miktionsurosonographie

Der Radiologe, 2021

Jörg D. Moritz · Doris Franke · Friederike Körber · Hans-JoachimMentzel 1 Kinderradiologie, Klini... more Jörg D. Moritz · Doris Franke · Friederike Körber · Hans-JoachimMentzel 1 Kinderradiologie, Klinik für Radiologie und Neuroradiologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Deutschland 2 Kinderklinik, Medizinische Hochschule Hannover, Hannover, Deutschland 3 Kinderradiologie, UniversitätsklinikumKöln, Köln, Deutschland 4 Kinderradiologie, Universitätsklinikum Jena, Jena, Deutschland

Research paper thumbnail of Radiologische Bildgebung des Neuroblastoms

Der Radiologe, 2021

Neuroblastome sind Tumoren des sympathischen Nervensystems, die im Bereich des Grenzstrangs und d... more Neuroblastome sind Tumoren des sympathischen Nervensystems, die im Bereich des Grenzstrangs und der Nebennieren wachsen. Sie sind bezüglich ihrer gewebespezifischen Zusammensetzungen, ihrer Molekulargenetik und damit insgesamt auch ihrer Prognose sehr unterschiedlich. Bei einer Inzidenz von 1:6000 machen die Neuroblastome einen Anteil von 5,5 % der kindlichen Tumoren aus. Sie treten zumeist bis zum Vorschulalter auf, das mittlere Erkrankungsalter beträgt 14 Monate. Erwachsene sind sehr selten betroffen. Die radiologische Bildgebung, insbesondere die Magnetresonanztomographie (MRT), spielt für die Diagnose, die Risikostratifizierung und die Therapiekontrolle eine essenzielle Rolle. Auf der Basis selektiver Literaturrecherche in der Datenbank PubMed, der Leitlinien und Studienprotokolle der nationalen und internationalen Fachgesellschaften werden die bildgebenden Standards sowie die neuesten Entwicklungen dargestellt. Die Bildgebung nimmt beim Neuroblastom aufgrund der heterogenen Pro...

Research paper thumbnail of Entzündungen des muskuloskelettalen Systems bei Kindern und Jugendlichen

Radiologie up2date, 2020

ZusammenfassungDas muskuloskelettale System unterliegt im Verlauf des Wachstums wie kaum ein ande... more ZusammenfassungDas muskuloskelettale System unterliegt im Verlauf des Wachstums wie kaum ein anderes Organsystem einem hohen Wandel. Entsprechend unterscheiden sich Entzündungen in Ausdehnung und Verlauf bei Kindern und Jugendlichen nicht nur von denen bei erwachsenen Patienten, sondern verändern sich auch während der Adoleszenz.

Research paper thumbnail of Das Kind mit akuten Bauchschmerzen in der Notaufnahme

Notaufnahme up2date, 2020

Research paper thumbnail of Early childhood height-adjusted total kidney volume as a risk marker of kidney survival in ARPKD

Scientific Reports, 2021

Autosomal recessive polycystic kidney disease (ARPKD) is characterized by bilateral fibrocystic c... more Autosomal recessive polycystic kidney disease (ARPKD) is characterized by bilateral fibrocystic changes resulting in pronounced kidney enlargement. Impairment of kidney function is highly variable and widely available prognostic markers are urgently needed as a base for clinical decision-making and future clinical trials. In this observational study we analyzed the longitudinal development of sonographic kidney measurements in a cohort of 456 ARPKD patients from the international registry study ARegPKD. We furthermore evaluated correlations of sonomorphometric findings and functional kidney disease with the aim to describe the natural disease course and to identify potential prognostic markers. Kidney pole-to-pole (PTP) length and estimated total kidney volume (eTKV) increase with growth throughout childhood and adolescence despite individual variability. Height-adjusted PTP length decreases over time, but such a trend cannot be seen for height-adjusted eTKV (haeTKV) where we even o...

Research paper thumbnail of The phenotypic spectrum of PCDH12 associated disorders - Five new cases and review of the literature

European Journal of Paediatric Neurology, 2021

PCDH12 is a member of the non-clustered protocadherin family of calcium-dependent cell adhesion p... more PCDH12 is a member of the non-clustered protocadherin family of calcium-dependent cell adhesion proteins, which are involved in the regulation of brain development and endothelial adhesion. To date, only 15 families have been reported with PCDH12 associated disease. The main features previously associated with PCDH12 deficiency are developmental delay, movement disorder, epilepsy, microcephaly, visual impairment, midbrain malformations, and intracranial calcifications. Here, we report novel clinical features such as onset of epilepsy after infancy, episodes of transient developmental regression, and dysplasia of the medulla oblongata associated with three different novel truncating PCDH12 mutations in five cases (three children, two adults) from three unrelated families. Interestingly, our data suggests a clinical overlap with interferonopathies, and we show an elevated interferon score in two pediatric patients. This case series expands the genetic and phenotypic spectrum of PCDH12 associated diseases and highlights the broad clinical variability.

Research paper thumbnail of Insulin Like Growth Factor 1 Moderates the Influence of the BDNF P.Val66Met Variant on Depression Severity in Adolescent Depression

Journal of Psychiatry and Psychiatric Disorder, 2020

Background: A genetic influence for adolescent depression has been described in numerous studies.... more Background: A genetic influence for adolescent depression has been described in numerous studies. The product of the brain-derived neurotrophic factor gene (BDNF; rs6265 c.196G>A; p.Val66Met) has been identified playing an important role in genesis and course of depression. It interacts with serological BDNF and other growth factors such as the Insulin-like-Growth Factor 1 (IGF-1), influencing memory-associated brain regions (i.e. hippocampus, parahippocampal gyrus and entorhinal cortex) as well as reward-related brain circuits (cf. nucleus accumbens, amygdala and frontal areas). Methods: 40 patients with adolescent depression aged 13 to 17 years, were included. Assuming a significant influence of the BDNF p.Val66Met variant on depression severity, we performed moderation analyses to further examine the interplay between BDNF p.Val66Met variant, serological IGF-1, regional brain volume and depression severity. Results: IGF-1 was found to moderate significantly the influence of BDNF p.Val66Met variant on depression severity. Brain volumes of (para) hippocampal, and amygdala as well as the nucleus accumbens moderated the same only in combination with IGF-1. Conclusions: We discuss the significant influence of serological IGF-1 and BDNF p.Val66Met variant in terms of neuroplasticity. We interpret the role of changes in memory and reward-related brain circuits as hints towards the localization of the interaction between BDNF p.Val66Met variant and IGF-1. Our findings point to a potential mechanism in juvenile depression which differs from actual models in adult depression and could in a further step contribute to targeted therapies for depressive adolescents.

Research paper thumbnail of Post-mortem estimation of gestational age and maturation of new-borns by CT examination of clavicle length, femoral length and femoral bone nuclei

Forensic Science International, 2020

Various parameters can be used for the estimation of gestational age and maturity with arising ch... more Various parameters can be used for the estimation of gestational age and maturity with arising challenges in the assessment of decomposed bodies. In order to assess gestational age and thus maturity, the study measured the femoral length, the diameter of the distal femoral epiphysis and the presence of the proximal tibial epiphysis compared to a known clavicle length. The resulting gestational ages were compared and statistically evaluated. As a result, discrepancies between the estimated gestational ages became apparent in some cases when comparing the individual structures to be measured. However, there was a clear tendency towards a lower gestational age calculated based on clavicle length and a higher gestational age calculated based on femoral length and distal femoral epiphysis. With regard to the assessment of maturity, it has been concluded that, if the proximal tibial epiphysis is present, maturity can also be assumed based on the diameter of the distal femoral epiphysis and the length of the femur.

Research paper thumbnail of Mutations of ADAMTS9 Cause Nephronophthisis-Related Ciliopathy

The American Journal of Human Genetics, 2019

Nephronophthisis-related ciliopathies (NPHP-RCs) are a group of inherited diseases that are assoc... more Nephronophthisis-related ciliopathies (NPHP-RCs) are a group of inherited diseases that are associated with defects in primary cilium structure and function. To identify genes mutated in NPHP-RC, we performed homozygosity mapping and whole-exome sequencing for >100 individuals, some of whom were single affected individuals born to consanguineous parents and some of whom were siblings of indexes who were also affected by NPHP-RC. We then performed high-throughput exon sequencing in a worldwide cohort of 800 additional families affected by NPHP-RC. We identified two ADAMTS9 mutations (c.4575_4576del [p.Gln1525Hisfs*60] and c.194C>G [p.Thr65Arg]) that appear to cause NPHP-RC. Although ADAMTS9 is known to be a secreted extracellular metalloproteinase, we found that ADAMTS9 localized near the basal bodies of primary cilia in the cytoplasm. Heterologously expressed wild-type ADAMTS9, in contrast to mutant proteins detected in individuals with NPHP-RC, localized to the vicinity of the basal body. Loss of ADAMTS9 resulted in shortened cilia and defective sonic hedgehog signaling. Knockout of Adamts9 in IMCD3 cells, followed by spheroid induction, resulted in defective lumen formation, which was rescued by an overexpression of wild-type, but not of mutant, ADAMTS9. Knockdown of adamts9 in zebrafish recapitulated NPHP-RC phenotypes, including renal cysts and hydrocephalus. These findings suggest that the identified mutations in ADAMTS9 cause NPHP-RC and that ADAMTS9 is required for the formation and function of primary cilia. Material and Methods Research Subjects Blood samples and pedigrees were obtained from individuals with diagnosed NPHP-RC after informed consent was provided.

Research paper thumbnail of Dominant SCN2A Mutation Causes Familial Episodic Ataxia and Impairment of Speech Development

Neuropediatrics, 2018

Mutations in SCN2A are associated with a heterogeneous clinical spectrum including epilepsy and a... more Mutations in SCN2A are associated with a heterogeneous clinical spectrum including epilepsy and autism. Here, we have identified a peculiar phenotype associated with vaccination related exacerbations of ataxia. We report the first family with three individuals affected by SCN2A-associated episodic ataxia (EA) with impaired speech development. The index patient manifested his first episode of subacute cerebellar ataxia at the age of 12 months, 3 weeks after vaccinations for measles, mumps, rubella, and varicella. Cranial magnetic resonance imaging showed a lesion of the left cerebellar hemisphere, which was first considered as a potential cause of the ataxia. The patient fully recovered within 3 weeks, but developed three very similar episodes of transient ataxia within the following 24 months. Whole exome sequencing of the index patient revealed a heterozygous autosomal-dominant mutation in SCN2A (NM_021007, c.4949T > C; p.L1650P), which was confirmed in the likewise affected mot...

Research paper thumbnail of Intranasal breast milk for premature infants with severe intraventricular hemorrhage—an observation

European Journal of Pediatrics, 2018

For nasal application of neurotrophins and mesenchymal stem cells, successful delivery to the bra... more For nasal application of neurotrophins and mesenchymal stem cells, successful delivery to the brain and therapeutic effects are known from experimental data in animals. Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. This is a first exploration on additional nasal breast milk and neuromorphological outcome after severe neonatal brain injury. We present a retrospective summary of 31 very low birth weight preterm infants with intraventricular hemorrhage°3/4 from one third-level neonatal center. All were breast milk fed. Sixteen infants additionally received nasal drops of fresh breast milk daily with informed parental consent for at least 28 days. Cerebral ultrasound courses were reviewed by a pediatric radiologist blinded to the intervention. The main outcome measure was severity of porencephalic defects before discharge. Clinical covariates were comparable in both groups. With nasal breast milk, a trend to a lower incidence for severe porencephalic defects (21% vs. 58%) was detected. Incidences were lower for progressive ventricular dilatation (71% vs. 91%) and surgery for posthemorrhagic hydrocephalus (50% vs. 67%). Conclusion: The hypothesis is generated that early intranasal application of breast milk could have a beneficial effect on neurodevelopment in preterm infants. Controlled investigation is needed. What is Known: • Successful delivery to the brain and therapeutic effects are known for nasal application of neurotrophins and mesenchymal stem cells from experimental data in animal studies. • Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. What is New: • This is the first report on additional nasal breast milk application in very low birth weight preterm infants with severe brain injury observing a trend for less severe porencephalic defects. • The hypothesis is generated that nasal breast milk might exert neuroprotective effects in preterm infants.

Research paper thumbnail of Chronic thrombocytopenia and skeletal dysplasia in a 14-year-old girl with cystic fibrosis

Clinical Case Reports and Reviews, 2016

Research paper thumbnail of Das Smith-Lemli-Opitz Syndrom – Fallbericht, Diagnostik, therapeutische Optionen

Zeitschrift für Geburtshilfe und Neonatologie, 2009

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal-recessive disease characterised by the combinat... more Smith-Lemli-Opitz syndrome (SLOS) is an autosomal-recessive disease characterised by the combination of (foetal) growth retardation, mental retardation and a typical malformation pattern. In particular, the combination of cardiovascular defects, Y-shaped syndactyly of the 2 (nd) and 3 (rd) toes and a distinctive craniofacial appearance, often including a cleft palate, are characteristic of SLOS. The disease is caused by a defect in cholesterol synthesis resulting in a reduced or absent activity of the enzyme 7-dehydrocholesterol reductase (DHCR7). As a consequence, a lack of cholesterol and an increase of toxic cholesterol precursors are observed in the majority of patients. We report on a female patient who was born at 37 weeks of gestation and was both small and light for gestational age who displayed typical signs of SLOS. After the diagnosis had been confirmed, a therapeutic approach with oral substitution of cholesterol and the administration of simvastatin was initiated. In spite of this strategy, the patient died at the age of 12 weeks from the disease. Based on the case presented, we review and discuss current diagnostic and therapeutic options for patients with SLOS.

Research paper thumbnail of Non-manifesting AHI1 truncations indicate localized loss-of-function tolerance in a severe Mendelian disease gene

Human Molecular Genetics, 2015

Determination of variant pathogenicity represents a major challenge in the era of high-throughput... more Determination of variant pathogenicity represents a major challenge in the era of high-throughput sequencing. Erroneous categorization may result if variants affect genes that are in fact dispensable. We demonstrate that this also applies to rare, apparently unambiguous truncating mutations of an established disease gene. By whole-exome sequencing (WES) in a consanguineous family with congenital non-syndromic deafness, we unexpectedly identified a homozygous nonsense variant, p.Arg1066*, in AHI1, a gene associated with Joubert syndrome (JBTS), a severe recessive ciliopathy. None of four homozygotes expressed any signs of JBTS, and one of them had normal hearing, which also ruled out p.Arg1066* as the cause of deafness. Homozygosity mapping and WES in the only other reported JBTS family with a homozygous C-terminal truncation (p.Trp1088Leufs*16) confirmed AHI1 as disease gene, but based on a more N-terminal missense mutation impairing WD40-repeat † These authors contributed equally to the study.

Research paper thumbnail of Isolated femoral hypoplasia: an intrauterine differential diagnosis to campomelia

Pediatric Radiology, 2005

When a possible congenital dysplasia has been identified, knowledge of specific syndromes is nece... more When a possible congenital dysplasia has been identified, knowledge of specific syndromes is necessary to decide the correct prenatal management. An important example of this is isolated femoral hypoplasia with femoral bowing as a differential diagnosis of campomelia. Four newborn babies with clinical and radiological findings are demonstrated. The differential diagnosis and a review of the literature are presented. Case reports Case 1 A male newborn was the first child of healthy nonconsanguineous parents. There was no family history of congenital limb deformities. Prenatal US showed bowing and shortening of the left femur (Fig. 1). The karyotype of the child was 46XY, with a mutation on the short arm of chromosome 7 which was also present

Research paper thumbnail of Referenz Endokrinologie und Diabetologie

Referenz Endokrinologie und Diabetologie, 2020

Research paper thumbnail of Nierenbeckenkelchsystemerweiterung und eine flüssigkeitsgefüllte Blase im Unterbauch

Monatsschrift Kinderheilkunde

Research paper thumbnail of Segmentale arterielle Mediolyse bei einem Neugeborenen mit Plazentabeteiligung

Zeitschrift für Geburtshilfe und Neonatologie, 2004

Research paper thumbnail of True thymic hyperplasia associated with severe thymic cyst bleeding in a newborn: case report and review of the literature

Annals of Diagnostic Pathology, 2007

We report on a 5-week-old male infant with recurrent respiratory distress since birth and congeni... more We report on a 5-week-old male infant with recurrent respiratory distress since birth and congenital thymic hyperplasia. Acute life-threatening thymic bleeding apparently from ruptured thymic cysts into the pleural spaces complicated the clinical situation. Thoracotomy and complete thymectomy were performed. Histologic examination revealed normal thymic architecture with cysts of different sizes and an increased thymic weight of 30 g. The combination of true thymic hyperplasia and cyst bleeding in a newborn has not been previously reported and will be discussed in relation to the available literature on respiratory distress due to thymic pathology in childhood.

Research paper thumbnail of Einfluss von intranasal verabreichter Muttermilch bei Frühgeborenen mit hochgradigen intraventrikulären Blutungen – erste sonografische Ergebnisse

RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2017

Research paper thumbnail of Standardisierte Durchführung der Miktionsurosonographie

Der Radiologe, 2021

Jörg D. Moritz · Doris Franke · Friederike Körber · Hans-JoachimMentzel 1 Kinderradiologie, Klini... more Jörg D. Moritz · Doris Franke · Friederike Körber · Hans-JoachimMentzel 1 Kinderradiologie, Klinik für Radiologie und Neuroradiologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Deutschland 2 Kinderklinik, Medizinische Hochschule Hannover, Hannover, Deutschland 3 Kinderradiologie, UniversitätsklinikumKöln, Köln, Deutschland 4 Kinderradiologie, Universitätsklinikum Jena, Jena, Deutschland

Research paper thumbnail of Radiologische Bildgebung des Neuroblastoms

Der Radiologe, 2021

Neuroblastome sind Tumoren des sympathischen Nervensystems, die im Bereich des Grenzstrangs und d... more Neuroblastome sind Tumoren des sympathischen Nervensystems, die im Bereich des Grenzstrangs und der Nebennieren wachsen. Sie sind bezüglich ihrer gewebespezifischen Zusammensetzungen, ihrer Molekulargenetik und damit insgesamt auch ihrer Prognose sehr unterschiedlich. Bei einer Inzidenz von 1:6000 machen die Neuroblastome einen Anteil von 5,5 % der kindlichen Tumoren aus. Sie treten zumeist bis zum Vorschulalter auf, das mittlere Erkrankungsalter beträgt 14 Monate. Erwachsene sind sehr selten betroffen. Die radiologische Bildgebung, insbesondere die Magnetresonanztomographie (MRT), spielt für die Diagnose, die Risikostratifizierung und die Therapiekontrolle eine essenzielle Rolle. Auf der Basis selektiver Literaturrecherche in der Datenbank PubMed, der Leitlinien und Studienprotokolle der nationalen und internationalen Fachgesellschaften werden die bildgebenden Standards sowie die neuesten Entwicklungen dargestellt. Die Bildgebung nimmt beim Neuroblastom aufgrund der heterogenen Pro...

Research paper thumbnail of Entzündungen des muskuloskelettalen Systems bei Kindern und Jugendlichen

Radiologie up2date, 2020

ZusammenfassungDas muskuloskelettale System unterliegt im Verlauf des Wachstums wie kaum ein ande... more ZusammenfassungDas muskuloskelettale System unterliegt im Verlauf des Wachstums wie kaum ein anderes Organsystem einem hohen Wandel. Entsprechend unterscheiden sich Entzündungen in Ausdehnung und Verlauf bei Kindern und Jugendlichen nicht nur von denen bei erwachsenen Patienten, sondern verändern sich auch während der Adoleszenz.

Research paper thumbnail of Das Kind mit akuten Bauchschmerzen in der Notaufnahme

Notaufnahme up2date, 2020

Research paper thumbnail of Early childhood height-adjusted total kidney volume as a risk marker of kidney survival in ARPKD

Scientific Reports, 2021

Autosomal recessive polycystic kidney disease (ARPKD) is characterized by bilateral fibrocystic c... more Autosomal recessive polycystic kidney disease (ARPKD) is characterized by bilateral fibrocystic changes resulting in pronounced kidney enlargement. Impairment of kidney function is highly variable and widely available prognostic markers are urgently needed as a base for clinical decision-making and future clinical trials. In this observational study we analyzed the longitudinal development of sonographic kidney measurements in a cohort of 456 ARPKD patients from the international registry study ARegPKD. We furthermore evaluated correlations of sonomorphometric findings and functional kidney disease with the aim to describe the natural disease course and to identify potential prognostic markers. Kidney pole-to-pole (PTP) length and estimated total kidney volume (eTKV) increase with growth throughout childhood and adolescence despite individual variability. Height-adjusted PTP length decreases over time, but such a trend cannot be seen for height-adjusted eTKV (haeTKV) where we even o...

Research paper thumbnail of The phenotypic spectrum of PCDH12 associated disorders - Five new cases and review of the literature

European Journal of Paediatric Neurology, 2021

PCDH12 is a member of the non-clustered protocadherin family of calcium-dependent cell adhesion p... more PCDH12 is a member of the non-clustered protocadherin family of calcium-dependent cell adhesion proteins, which are involved in the regulation of brain development and endothelial adhesion. To date, only 15 families have been reported with PCDH12 associated disease. The main features previously associated with PCDH12 deficiency are developmental delay, movement disorder, epilepsy, microcephaly, visual impairment, midbrain malformations, and intracranial calcifications. Here, we report novel clinical features such as onset of epilepsy after infancy, episodes of transient developmental regression, and dysplasia of the medulla oblongata associated with three different novel truncating PCDH12 mutations in five cases (three children, two adults) from three unrelated families. Interestingly, our data suggests a clinical overlap with interferonopathies, and we show an elevated interferon score in two pediatric patients. This case series expands the genetic and phenotypic spectrum of PCDH12 associated diseases and highlights the broad clinical variability.

Research paper thumbnail of Insulin Like Growth Factor 1 Moderates the Influence of the BDNF P.Val66Met Variant on Depression Severity in Adolescent Depression

Journal of Psychiatry and Psychiatric Disorder, 2020

Background: A genetic influence for adolescent depression has been described in numerous studies.... more Background: A genetic influence for adolescent depression has been described in numerous studies. The product of the brain-derived neurotrophic factor gene (BDNF; rs6265 c.196G>A; p.Val66Met) has been identified playing an important role in genesis and course of depression. It interacts with serological BDNF and other growth factors such as the Insulin-like-Growth Factor 1 (IGF-1), influencing memory-associated brain regions (i.e. hippocampus, parahippocampal gyrus and entorhinal cortex) as well as reward-related brain circuits (cf. nucleus accumbens, amygdala and frontal areas). Methods: 40 patients with adolescent depression aged 13 to 17 years, were included. Assuming a significant influence of the BDNF p.Val66Met variant on depression severity, we performed moderation analyses to further examine the interplay between BDNF p.Val66Met variant, serological IGF-1, regional brain volume and depression severity. Results: IGF-1 was found to moderate significantly the influence of BDNF p.Val66Met variant on depression severity. Brain volumes of (para) hippocampal, and amygdala as well as the nucleus accumbens moderated the same only in combination with IGF-1. Conclusions: We discuss the significant influence of serological IGF-1 and BDNF p.Val66Met variant in terms of neuroplasticity. We interpret the role of changes in memory and reward-related brain circuits as hints towards the localization of the interaction between BDNF p.Val66Met variant and IGF-1. Our findings point to a potential mechanism in juvenile depression which differs from actual models in adult depression and could in a further step contribute to targeted therapies for depressive adolescents.

Research paper thumbnail of Post-mortem estimation of gestational age and maturation of new-borns by CT examination of clavicle length, femoral length and femoral bone nuclei

Forensic Science International, 2020

Various parameters can be used for the estimation of gestational age and maturity with arising ch... more Various parameters can be used for the estimation of gestational age and maturity with arising challenges in the assessment of decomposed bodies. In order to assess gestational age and thus maturity, the study measured the femoral length, the diameter of the distal femoral epiphysis and the presence of the proximal tibial epiphysis compared to a known clavicle length. The resulting gestational ages were compared and statistically evaluated. As a result, discrepancies between the estimated gestational ages became apparent in some cases when comparing the individual structures to be measured. However, there was a clear tendency towards a lower gestational age calculated based on clavicle length and a higher gestational age calculated based on femoral length and distal femoral epiphysis. With regard to the assessment of maturity, it has been concluded that, if the proximal tibial epiphysis is present, maturity can also be assumed based on the diameter of the distal femoral epiphysis and the length of the femur.

Research paper thumbnail of Mutations of ADAMTS9 Cause Nephronophthisis-Related Ciliopathy

The American Journal of Human Genetics, 2019

Nephronophthisis-related ciliopathies (NPHP-RCs) are a group of inherited diseases that are assoc... more Nephronophthisis-related ciliopathies (NPHP-RCs) are a group of inherited diseases that are associated with defects in primary cilium structure and function. To identify genes mutated in NPHP-RC, we performed homozygosity mapping and whole-exome sequencing for >100 individuals, some of whom were single affected individuals born to consanguineous parents and some of whom were siblings of indexes who were also affected by NPHP-RC. We then performed high-throughput exon sequencing in a worldwide cohort of 800 additional families affected by NPHP-RC. We identified two ADAMTS9 mutations (c.4575_4576del [p.Gln1525Hisfs*60] and c.194C>G [p.Thr65Arg]) that appear to cause NPHP-RC. Although ADAMTS9 is known to be a secreted extracellular metalloproteinase, we found that ADAMTS9 localized near the basal bodies of primary cilia in the cytoplasm. Heterologously expressed wild-type ADAMTS9, in contrast to mutant proteins detected in individuals with NPHP-RC, localized to the vicinity of the basal body. Loss of ADAMTS9 resulted in shortened cilia and defective sonic hedgehog signaling. Knockout of Adamts9 in IMCD3 cells, followed by spheroid induction, resulted in defective lumen formation, which was rescued by an overexpression of wild-type, but not of mutant, ADAMTS9. Knockdown of adamts9 in zebrafish recapitulated NPHP-RC phenotypes, including renal cysts and hydrocephalus. These findings suggest that the identified mutations in ADAMTS9 cause NPHP-RC and that ADAMTS9 is required for the formation and function of primary cilia. Material and Methods Research Subjects Blood samples and pedigrees were obtained from individuals with diagnosed NPHP-RC after informed consent was provided.

Research paper thumbnail of Dominant SCN2A Mutation Causes Familial Episodic Ataxia and Impairment of Speech Development

Neuropediatrics, 2018

Mutations in SCN2A are associated with a heterogeneous clinical spectrum including epilepsy and a... more Mutations in SCN2A are associated with a heterogeneous clinical spectrum including epilepsy and autism. Here, we have identified a peculiar phenotype associated with vaccination related exacerbations of ataxia. We report the first family with three individuals affected by SCN2A-associated episodic ataxia (EA) with impaired speech development. The index patient manifested his first episode of subacute cerebellar ataxia at the age of 12 months, 3 weeks after vaccinations for measles, mumps, rubella, and varicella. Cranial magnetic resonance imaging showed a lesion of the left cerebellar hemisphere, which was first considered as a potential cause of the ataxia. The patient fully recovered within 3 weeks, but developed three very similar episodes of transient ataxia within the following 24 months. Whole exome sequencing of the index patient revealed a heterozygous autosomal-dominant mutation in SCN2A (NM_021007, c.4949T > C; p.L1650P), which was confirmed in the likewise affected mot...

Research paper thumbnail of Intranasal breast milk for premature infants with severe intraventricular hemorrhage—an observation

European Journal of Pediatrics, 2018

For nasal application of neurotrophins and mesenchymal stem cells, successful delivery to the bra... more For nasal application of neurotrophins and mesenchymal stem cells, successful delivery to the brain and therapeutic effects are known from experimental data in animals. Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. This is a first exploration on additional nasal breast milk and neuromorphological outcome after severe neonatal brain injury. We present a retrospective summary of 31 very low birth weight preterm infants with intraventricular hemorrhage°3/4 from one third-level neonatal center. All were breast milk fed. Sixteen infants additionally received nasal drops of fresh breast milk daily with informed parental consent for at least 28 days. Cerebral ultrasound courses were reviewed by a pediatric radiologist blinded to the intervention. The main outcome measure was severity of porencephalic defects before discharge. Clinical covariates were comparable in both groups. With nasal breast milk, a trend to a lower incidence for severe porencephalic defects (21% vs. 58%) was detected. Incidences were lower for progressive ventricular dilatation (71% vs. 91%) and surgery for posthemorrhagic hydrocephalus (50% vs. 67%). Conclusion: The hypothesis is generated that early intranasal application of breast milk could have a beneficial effect on neurodevelopment in preterm infants. Controlled investigation is needed. What is Known: • Successful delivery to the brain and therapeutic effects are known for nasal application of neurotrophins and mesenchymal stem cells from experimental data in animal studies. • Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. What is New: • This is the first report on additional nasal breast milk application in very low birth weight preterm infants with severe brain injury observing a trend for less severe porencephalic defects. • The hypothesis is generated that nasal breast milk might exert neuroprotective effects in preterm infants.

Research paper thumbnail of Chronic thrombocytopenia and skeletal dysplasia in a 14-year-old girl with cystic fibrosis

Clinical Case Reports and Reviews, 2016

Research paper thumbnail of Das Smith-Lemli-Opitz Syndrom – Fallbericht, Diagnostik, therapeutische Optionen

Zeitschrift für Geburtshilfe und Neonatologie, 2009

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal-recessive disease characterised by the combinat... more Smith-Lemli-Opitz syndrome (SLOS) is an autosomal-recessive disease characterised by the combination of (foetal) growth retardation, mental retardation and a typical malformation pattern. In particular, the combination of cardiovascular defects, Y-shaped syndactyly of the 2 (nd) and 3 (rd) toes and a distinctive craniofacial appearance, often including a cleft palate, are characteristic of SLOS. The disease is caused by a defect in cholesterol synthesis resulting in a reduced or absent activity of the enzyme 7-dehydrocholesterol reductase (DHCR7). As a consequence, a lack of cholesterol and an increase of toxic cholesterol precursors are observed in the majority of patients. We report on a female patient who was born at 37 weeks of gestation and was both small and light for gestational age who displayed typical signs of SLOS. After the diagnosis had been confirmed, a therapeutic approach with oral substitution of cholesterol and the administration of simvastatin was initiated. In spite of this strategy, the patient died at the age of 12 weeks from the disease. Based on the case presented, we review and discuss current diagnostic and therapeutic options for patients with SLOS.

Research paper thumbnail of Non-manifesting AHI1 truncations indicate localized loss-of-function tolerance in a severe Mendelian disease gene

Human Molecular Genetics, 2015

Determination of variant pathogenicity represents a major challenge in the era of high-throughput... more Determination of variant pathogenicity represents a major challenge in the era of high-throughput sequencing. Erroneous categorization may result if variants affect genes that are in fact dispensable. We demonstrate that this also applies to rare, apparently unambiguous truncating mutations of an established disease gene. By whole-exome sequencing (WES) in a consanguineous family with congenital non-syndromic deafness, we unexpectedly identified a homozygous nonsense variant, p.Arg1066*, in AHI1, a gene associated with Joubert syndrome (JBTS), a severe recessive ciliopathy. None of four homozygotes expressed any signs of JBTS, and one of them had normal hearing, which also ruled out p.Arg1066* as the cause of deafness. Homozygosity mapping and WES in the only other reported JBTS family with a homozygous C-terminal truncation (p.Trp1088Leufs*16) confirmed AHI1 as disease gene, but based on a more N-terminal missense mutation impairing WD40-repeat † These authors contributed equally to the study.

Research paper thumbnail of Isolated femoral hypoplasia: an intrauterine differential diagnosis to campomelia

Pediatric Radiology, 2005

When a possible congenital dysplasia has been identified, knowledge of specific syndromes is nece... more When a possible congenital dysplasia has been identified, knowledge of specific syndromes is necessary to decide the correct prenatal management. An important example of this is isolated femoral hypoplasia with femoral bowing as a differential diagnosis of campomelia. Four newborn babies with clinical and radiological findings are demonstrated. The differential diagnosis and a review of the literature are presented. Case reports Case 1 A male newborn was the first child of healthy nonconsanguineous parents. There was no family history of congenital limb deformities. Prenatal US showed bowing and shortening of the left femur (Fig. 1). The karyotype of the child was 46XY, with a mutation on the short arm of chromosome 7 which was also present