Peter Aerssens - Academia.edu (original) (raw)

Papers by Peter Aerssens

Journal of Medical Genetics, Jan 13, 2020

BackgroundIntragenic NRXN1 deletions are susceptibility variants for neurodevelopmental disorders... more BackgroundIntragenic NRXN1 deletions are susceptibility variants for neurodevelopmental disorders; however, their clinical interpretation is often unclear. Therefore, a literature study and an analysis of 43 previously unpublished deletions are provided.MethodsThe literature cohort covered 629 heterozygous NRXN1 deletions: 148 in controls, 341 in probands and 140 in carrier relatives, and was used for clinical hypothesis testing. Exact breakpoint determination was performed for 43 in-house deletions.ResultsThe prevalence of exonic NRXN1 deletions in controls was ~1/3000 as compared with ~1/800 in patients with neurodevelopmental/neuropsychiatric disorders. The differential distribution of deletions across the gene between controls and probands allowed to distinguish distinct areas within the gene. Exon 6–24 deletions appeared only twice in over 100000 control individuals, had an estimated penetrance for neurodevelopmental disorders of 32.43%, a de novo rate of 50% and segregated mainly with intellectual disability (ID) and schizophrenia. In contrast, exon 1–5 deletions appeared in 20 control individuals, had an estimated penetrance of 12.59%, a de novo rate of 32.5% and were reported with a broad range of neurodevelopmental phenotypes. Exact breakpoint determination revealed six recurrent intron 5 deletions.ConclusionExon 6–24 deletions have a high penetrance and are mainly associated with ID and schizophrenia. In contrast, the actual contribution of exon 1–5 deletions to a neurodevelopmental/neuropsychiatric disorder in an individual patient and family remains very difficult to assess. To enhance the clinical interpretation, this study provides practical considerations for counselling and an interactive table for comparing a deletion of interest with the available literature data.

Pediatric Research, May 1, 1999

Pediatric Research, Sep 1, 1996

Hormone Research 53(Suppl, Jul 14, 2000

Genetic counseling (Geneva, Switzerland), 2005

European Journal of Paediatric Neurology, 2013

Tijdschrift voor Geneeskunde, 2001

Human Mutation, 2010

L-2-Hydroxyglutaric aciduria (L2HGA) is a rare, neurometabolic disorder with an autosomal recessi... more L-2-Hydroxyglutaric aciduria (L2HGA) is a rare, neurometabolic disorder with an autosomal recessive mode of inheritance. Affected individuals only have neurological manifestations, including psychomotor retardation, cerebellar ataxia, and more variably macrocephaly, or epilepsy. The diagnosis of L2HGA can be made based on magnetic resonance imaging (MRI), biochemical analysis, and mutational analysis of L2HGDH. About 200 patients with elevated concentrations of 2-hydroxyglutarate (2HG) in the urine were referred for chiral determination of 2HG and L2HGDH mutational analysis. All patients with increased L2HG (n=106; 83 families) were included. Clinical information on 61 patients was obtained via questionnaires. In 82 families the mutations were detected by direct sequence analysis and/or multiplex ligation dependent probe amplification (MLPA), including one case where MLPA was essential to detect the second allele. In another case RT-PCR followed by deep intronic sequencing was needed to detect the mutation. Thirty-five novel mutations as well as 35 reported mutations and 14 nondisease-related variants are reviewed and included in a novel Leiden Open source Variation Database (LOVD) for L2HGDH variants (http://www.LOVD.nl/L2HGDH). Every user can access the database and submit variants/patients. Furthermore, we report on the phenotype, including neurological manifestations and urinary levels of L2HG, and we evaluate the phenotype-genotype relationship.

European Journal of Pediatrics, 2007

The Belgian Institute of Public Health registered from 2000 to 2005 a yearly average of 6,790 hos... more The Belgian Institute of Public Health registered from 2000 to 2005 a yearly average of 6,790 hospital admissions for rotavirus gastroenteritis in children less than 5 years of age. Very efficacious rotavirus vaccines are available nowadays. The surveillance of hospitalisation due to rotavirus gastroenteritis is a good target for the follow-up of vaccine-related prevention. In a large regional Belgian hospital, rotavirus is associated with 12% to 21% of all hospitalisation days among children less than 2 years of age. The general implementation of rotavirus vaccination could dramatically reduce the hospitalisation of young children due to rotavirus gastroenteritis in developed countries.

European Journal of Pediatrics, 2003

European Journal of Medical Genetics, 2005

A dysmorphic boy with severe mental retardation was found on array CGH to have an insertional tra... more A dysmorphic boy with severe mental retardation was found on array CGH to have an insertional translocation of chromosome 16p13.3 into the short arm of chromosome 22, karyotype 46,XY,.ish der(22),ins(22;16)(p13;p13.3p13.3) de novo. His clinical features overlap with the reported cases of 'duplication 16p' syndrome, namely a round face, hypertelorism, a long philtrum, micrognathia, a thin upper lip, a posterior cleft palate and low set, simple ears, clubbed feet, severe developmental delay, psychomotor retardation and seizures. This 4-year boy with trisomy 16p13.3 has the smallest duplication reported of this critical region, which could not be detected without array CGH. The maximal duplicated region is gene rich and contains about 80 genes and/or candidate genes. Assignment of the genes that contribute to the observed phenotype awaits the characterisation of other patients with small duplications in this region.

BMC family practice, Jan 26, 2005

Early diagnosis of serious infections in children is difficult in general practice, as incidence ... more Early diagnosis of serious infections in children is difficult in general practice, as incidence is low, patients present themselves at an early stage of the disease and diagnostic tools are limited to signs and symptoms from observation, clinical history and physical examination. Little is known which signs and symptoms are important in general practice. With this qualitative study, we aimed to identify possible new important diagnostic variables. Semi-structured interviews with parents and physicians of children with a serious infection. We investigated all signs and symptoms that were related to or preceded the diagnosis. The analysis was done according to the grounded theory approach. Participants were recruited in general practice and at the hospital. 18 children who were hospitalised because of a serious infection were included. On average, parents and paediatricians were interviewed 3 days after admittance of the child to hospital, general practitioners between 5 and 8 days a...

Clinical Dysmorphology

Case study The proband is the second child of unrelated parents. She was born at term by caesarea... more Case study The proband is the second child of unrelated parents. She was born at term by caesarean section with a birth weight of 2800 g (−1.6 SD) and a length of 46 cm (−2.2 SD). The pregnancy was complicated by hypertension caused by IgA nephropathy for which the mother was treated with labetalol. Neonatal screening revealed elevated thyroid-stimulating hormone (TSH) levels indicating congenital hypothyroidism. Treatment with L-thyroxine was started at the age of 14 days. There was neonatal hypotonia, feeding difficulties and failure to thrive. At the age of 2 years there was short stature (–1.7 SD), peculiar facial features as described at an older age and behaviour characterized by emotional instability, temper tantrums (often in response to frustration), social anxiety, poor attention span and hyperactivity. She had delayed motor milestones with standing with support at 12 months and crawling at 18–19 months. She was raised in a bilingual environment (Flemish/English). Her speech was slightly delayed with first words at 1 year 10 months and difficulties with articulation until the age of 5 years. However, she had good language abilities later on. At age 7 years 4 months, she was clinically assessed because of concerns about her academic progress (particularly within the domain of mathematics) as well as fine and gross motor difficulties, problems with attention and focus, and social skill delays. On examination, she had peculiar facial features (Fig. 1 at age 10), short stature with height 119.5 cm (−1.1 SD) and weight 23.0 kg (−0.4 SD). Currently at the age of 11 years, she follows regular school with some educational support for mathematics mainly because of problems with automatization. She still has fine motor problems: poor handwriting, slower pace, and problems with routine daily motor tasks.

Journal of Medical Genetics

Tijdschrift voor Geneeskunde, 1998