Ivona Sansović - Academia.edu (original) (raw)

Papers by Ivona Sansović

PubMed, Jun 13, 2024

Aim: To determine the spectrum and frequency of disease-causing variants in patients with non-syn... more Aim: To determine the spectrum and frequency of disease-causing variants in patients with non-syndromic hearing loss (NSHL) and to investigate the diagnostic yield of the applied genetic methods. Methods: The study enrolled 306 unrelated patients with childhood-onset, mild-to-profound NSHL referred to Children's Hospital Zagreb for genetic testing between March 2006 and October 2023. The GJB2 variants were analyzed with the multiplex ligation-dependent probe amplification method and Sanger sequencing of the coding region of the GJB2 gene. In 21 patients negative for GJB2 biallelic variants, clinical exome sequencing (CES) was performed. Results: Among 234 disease-associated GJB2 alleles detected, 19 were clinically relevant, of which 18 were reported as pathogenic/likely pathogenic. The c.35delG variant accounted for 73.5% of the mutated alleles. More than half of the patients with biallelic GJB2 variants (64/110, 58.2%) were 35delG homozygotes. Seventeen non-GJB2 variants were found in 10 genes (TECTA, NOG, SLC26A4, PCDH15, TMPRSS3, USH2A, GATA3, MYO15A, SOX10, COL2A1) in 11 participants, and 5 variants (in TECTA, NOG, PCDH15, and SOX10) were novel (29.4%). Conclusion: We were able to elucidate the genetic cause of hearing loss in 121 patients, with an overall diagnostic rate of 39.5%. The c.35delG was the most common variant. CES allowed us to diagnose almost half of the patients with HL; to distinguish NSHL from the syndromic form of HL in cases where the phenotype was unclear or where symptoms were absent from an early age; and to discover novel variants.

PubMed, Oct 30, 2023

Missense variants in the α-tectorin gene (TECTA) cause autosomal dominant (DFNA8/A12) non-syndrom... more Missense variants in the α-tectorin gene (TECTA) cause autosomal dominant (DFNA8/A12) non-syndromic hearing loss (ADNSHL) and account for a considerable number of ADNSHL cases. According to genotype-phenotype correlation studies, missense variants in the zona pellucida (ZP) domain of α-tectorin predominantly cause mid-frequency HL. Here, we report on clinical exome sequencing results in a large family with early-onset, sensorineural, moderate-to-severe mid-frequency HL. We identified one heterozygous c.6183G>T variant near the ZP domain of TECTA segregating in five family members. This variant was previously reported as a variant of uncertain significance in a family with ADNSHL. On the basis of specific segregation in the currently studied family and the general guidelines of the American College of Medical Genetics and Genomics, we argue that the TECTA c.6183G>T variant should be considered a likely pathogenic cause of ADNSHL. This report adds to the knowledge on the rare c.6183G>T missense variant, which affects the immediate vicinity of the ZP domain in TECTA. Our findings highlight the importance of clinical evaluation in patients with familial HL and of studying family segregation when assessing the pathogenicity of a variant.

Croatian Medical Journal, Sep 30, 2023

The first case report of distal 16p12.1p11.2 trisomy and proximal 16p11.2 tetrasomy inherited fro... more The first case report of distal 16p12.1p11.2 trisomy and proximal 16p11.2 tetrasomy inherited from both parents CASE REPORT

Croatian Medical Journal, Sep 30, 2023

Missense variants in the α-tectorin gene (TECTA) cause autosomal dominant (DFNA8/A12) non-syndrom... more Missense variants in the α-tectorin gene (TECTA) cause autosomal dominant (DFNA8/A12) non-syndromic hearing loss (ADNSHL) and account for a considerable number of ADNSHL cases. According to genotype-phenotype correlation studies, missense variants in the zona pellucida (ZP) domain of α-tectorin predominantly cause mid-frequency HL. Here, we report on clinical exome sequencing results in a large family with early-onset, sensorineural, moderate-to-severe mid-frequency HL. We identified one heterozygous c.6183G>T variant near the ZP domain of TECTA segregating in five family members. This variant was previously reported as a variant of uncertain significance in a family with ADNSHL. On the basis of specific segregation in the currently studied family and the general guidelines of the American College of Medical Genetics and Genomics, we argue that the TECTA c.6183G>T variant should be considered a likely pathogenic cause of ADNSHL. This report adds to the knowledge on the rare c.6183G>T missense variant, which affects the immediate vicinity of the ZP domain in TECTA. Our findings highlight the importance of clinical evaluation in patients with familial HL and of studying family segregation when assessing the pathogenicity of a variant.

Paediatria Croatica, 2004

Dicentrics are chromosomes with two centromeres. This structurally aberrant chromosomes are highl... more Dicentrics are chromosomes with two centromeres. This structurally aberrant chromosomes are highly unstable, and rare constant member of the human karyotype. On the other hand, stable dicentrics usually present one active and one inactivate centromere and behave like monocentrics. The investigation conducted so far disclosed several types and different mechanisms of origin of dicentric chromosomes. In this report we present the results of cytogenetic and molecular study in a 5-years old girl with mild dismorphism, growth retardation, behavioral problems and structural rearrangement of X chromosome. Cytogenetic analysis was performed on short-term lymphocyte cultures of the proband and her parents. Chromosomes were GTG and CBG banded, while X chromosome inactivation was studied using RBG method. Fluorescence in situ hybridisation (FISH) was carried out on patients metaphase chromosomes and interphase cells with X chromosome painting and centromeric probes. The parental origin of aberrant chromosome was investigated by DNA polymorphisms analysis. Barr body analysis was performed on buccal mucosa smears stained by routine acetic orcein. Both parents presented normal karyotype. Leukocyte chromosome analyisis of the proband revealed one normal and one aberrant X chromosome. The rearranged X is a large submetacentric with one primary constriction and two blocks of C-staining. FISH analysis revealed that aberrant chromosome is composed entirely of the X chromosome material. Interphase FISH with alpha satellite X centromere probe revealed two mosaic cell lines. Three signals were observed in 84.5%, and one signal in 15.5% of interphase cells. Replication analysis showed that the normal X always early replicates, while the dicentric was late replicating in all investigated cells. The buccal smear revealed X-chromosome positive cells, and in some cells the Barr body was bipartite. Molecular analysis of DNA polymorphisms indicates that the dicentric is of paternal origin. Based on this study the karyotype of the patients is 45, X/46, X, psu idic(X)(q22.3), with the trisomy Xpter-q22.3 and monosomy Xqter-q22.3. We suggest that dicentric X is the result of isolocal break in the two chromatides of the paternal X chromosome, subsequent rejoining of broken ends, followed by inactivation of one centromere.

Fenomen odbijanja cijepljenja nazivamo antivakcinacijskim stavom, a širenje antivakcinacijskim po... more Fenomen odbijanja cijepljenja nazivamo antivakcinacijskim stavom, a širenje antivakcinacijskim pokretom ili kampanjom. Pritom oni koji odbijaju cijepljenje zapravo ne razumiju motive onih koji ih od cijepljenja odgovaraju, ali se brane da to rade zato jer sumnjaju ili ne razumiju argumente onih koji ih na cijepljenje nagovaraju. Cijepljenje se odbija iz međusobno logički i stručno suprotstavljenih argumenata. Riječ je o stručnoj shizmi u kojoj nema oblikovane ni transparente osnove, već se homogenizacija protiv cijepljenja zasniva na mnogo različitih i često suprotstavljenih kritika/negacija cjepiva, cijepljenja, struke, establišmenta, zakonske regulative, biznisa i farmaceutske industrije. Antivakcinacijski pokret došao je i do Hrvatske. U nascentnoj situaciji trebalo bi zaštititi cjepitelje od materijalne ili kaznene odgovornosti za još i sad obveznu preventivnu mjeru, te hitnim i razgovijetnim mjerama edukacije i javne promidžbe osigurati održanje adekvatnog obuhvata za postojeća cjepiva iz obveznog programa. Uz to treba osnovati odštetni fond za nuspojave cijepljenja. Umjesto sankcije za odbijanje cijepljenja treba uvesti obvezu posebnog dopunskog osiguranja za rizik svake bolesti za koju roditelj odbije cijepiti svoje dijete. U današnjoj situaciji prikladni odgovor bio bi i uvođenje novog cjepiva u program univerzalnog cijepljenja (npr. cijepljenje protiv rotavirusa ili pneumokokne bolesti).

European journal of medical genetics, Jan 16, 2018

Beckwith Wiedemann syndrome is a complex developmental disorder characterized by somatic overgrow... more Beckwith Wiedemann syndrome is a complex developmental disorder characterized by somatic overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycemia, and predisposition to embryonal tumors. We present epidemiological and clinical aspects of patients with Beckwith Wiedemann syndrome diagnosed prenatally or in the early years of life, using data from EUROCAT (European Surveillance of Congenital Anomalies) registries. The study population consisted of 371 cases identified between January 1990 and December 2015 in 34 registries from 16 European countries. There were 15 (4.0%) terminations of pregnancy after prenatal detection of severe anomaly/anomalies, 10 fetal deaths (2.7%), and 346 (93.3%) live-births. Twelve (3.6%) of the 330 live-births with available information on survival died in the first week of life, of those eleven (91.6%) were preterm. First-year survival rate was 90.9%. Prematurity was present in 40.6% of males and 33.9% of females. Macrosomia was found in 49....

World Journal of Pediatric Surgery

ObjectiveUndescended testes (UDT) is the most common anomaly of the male genitourinary tract. The... more ObjectiveUndescended testes (UDT) is the most common anomaly of the male genitourinary tract. The guidelines suggest that orchidopexy in congenitally UDT should be performed between 6 months and 18 months of age, while in acquired UDT, orchidopexy should be performed before puberty. Delay in treatment increases the risk of cancer and infertility. The main aim of this study was to determine whether we meet international standards in the treatment of UDT.MethodsThe present study included all boys who underwent orchidopexy either due to congenital or acquired UDT in 2019 (from January 1 to December 31). For each group, laterality, location, associated anomalies, premature birth and in how many cases ultrasound was applied were determined. Additionally, for each group, the types of surgery, the number of necessary reoperations, and in how many cases atrophy occurred were determined. Finally, ages of referral, of clinical examination, and of orchidopexy were determined.ResultsDuring this...

American Journal of Medical Genetics, 2004

We report a 19-year-old woman with minor craniofacial anomalies, mild mental retardation, and for... more We report a 19-year-old woman with minor craniofacial anomalies, mild mental retardation, and foramina parietalia permagna (FPP) (OMIM 168500). Cytogenetic analysis showed a de novo interstitial chromosome 22 long arm duplication. FISH with a panel of chromosome 22q12-q13 bands-specific BAC clones refined the cytogenetic investigation, and restricted the duplicated segment to the q12 region. Mutation analysis of FPP genes identified an insertion mutation in the ALX4 gene (344insC) in the proband and her father with loss of function of the gene. The patient's phenotype is considered in the light of the results of the cytogenetic, FISH, and molecular investigations, and her features are compared with those of other patients with similar duplications. Finally, variable phenotypic findings due to different 22q duplicated chromosomal segments are discussed. Our report indicates that 22q12 interstitial duplications are associated with craniofacial anomalies and mild mental retardation, while life threatening malformations are usually not present. Although these phenotypic changes are common and non-specific, molecular study of our patient established more precise relationships between clinical findings and 22q duplicated region(s). This approach fosters better counseling of the families of patients with newly diagnosed, similar duplications.

9. hrvatski biološki kongres s međunarodnim sudjelovanjem, 2006

Paediatria Croatica, 2004

Trisomija kratkog kraka kromosoma 12 rijetka je pojava u humanoj patologiji s ucestaloscu od 1 : ... more Trisomija kratkog kraka kromosoma 12 rijetka je pojava u humanoj patologiji s ucestaloscu od 1 : 50.000 novorođenih. U ovom radu prikazujemo djevojcicu u dobi od 2 godine i 11 mjeseci primljenu na geneticku obradu zbog dismorfije i razvojnog zaostajanja. Analizom prometafaznih kromosoma bolesnice određen je kariotip: 46, XX, der(5), t(5 ; 12)(5p15.3 ; 12p12.2)mat. Molekularna ispitivanja mikrosatelitnim markerima u podrucju mjesta loma potvrdila su trisomiju kratkog kraka kromosoma 12 u regiji 12p12.2, dok je mjesto loma kratkoga kraka kromosoma 5 u regiji 5p15.33 uputilo na terminalnu delecije manju od 3.1 Mb, smjestenu distalno od kriticnog segmenta za fenotip cri du chat. Premda je bolesnica imala fenotipska obilježja kako parcijanle trisomije 12p, tako i monosomije 5p, molekularna analiza je uputila na to da je kod djevojcice rijec o cistoj trisomiji 12p12.2 koja je klinicki vrlo nalik na fenotip cri du chat.

Etiologija slusnog ostecenja vrlo je raznolika. Vanjski cimbenici uzrokom su oko 40% slusnih oste... more Etiologija slusnog ostecenja vrlo je raznolika. Vanjski cimbenici uzrokom su oko 40% slusnih ostecenja, dok je oko 60% ostecenja sluha uzrokovano genetickim cimbenicima. Oko 20-50% nasljedne nesindromske zamjedbene gluhoce uzrokovano je mutacijama u genima GJB2 i GJB6. Zastupljenost pojedinih mutacija pokazuje regionalne razlike. Cilj: 1) provesti prospektivno istraživanje etiologije slusnog ostecenja u grupi osoba trajnim ostecenjem sluha obrađenih u Ambulanti za klinicku genetiku 2) utvrditi ucestalost mutacija gena GJB2 i GJB6 u populaciji hrvatskih bolesnika sa NSHL 3) predložiti optimalan model organizacije infrastrukture i nacina obrade prirođenog slusnog ostecenja kod djece dijagnosticirane putem sveobuhvatnog novorođenackog probira u Hrvatskoj. Rezultati: tijekom 2003. godine obradili smo 148 djece s ostecenjem sluha, 36 s provodnom nagluhosti, 92 sa zamjedbenom, te 20 s mijesanom nagluhosti. U 14 (9, 6%) utvrđeni su vanjski cimbenici kao najvjerojatniji uzrok slusnog ostece...

Monosomija 18p je jedna od najcescih delecija autosoma. Klinicko pojavljivanje 18p je veoma varij... more Monosomija 18p je jedna od najcescih delecija autosoma. Klinicko pojavljivanje 18p je veoma varijabilno. U vecini opisanih bolesnika monosomija je posljedica terminalne delecije, dok je u relativno malom broju slucajeva rezultat de novo translokacije. Nebalansirana translokacija citavog kraka kromosoma 18 obicno zahvaca akrocentricne kromosome 21 i 22. Mehanizam nastanka kromosomskog poremecaja nije jasan i predmet je znanstvenog interesa. U ovom radu prikazujemo rezultate klinickih i citogenetickih ispitivanja u djevojcice s parcijalnom monosomijom 18p. Nasa pacijentica je 8 godina stara djevojcica s mentalnom retardacijom i dismorfijom. Citogenetska analiza je izvrsena na preparatima dobivenim kratkotrajnom kulturom stanica periferne krvi. Koristili smo GTG-metodu identifikacije prometafaznih kromosoma i FISH metodu s pomocu specificnih probi za identifikaciju kromosoma 15 i 18. ToTelVysion Multi-color DNA Probe Mixtures za analizu subtelomernih regija i probe Prader Willi/Angelma...

Paediatria Croatica, 2007

Hearing loss is one of the most common congenital disorders affecting 1 to 3 of 1000 newborns. NS... more Hearing loss is one of the most common congenital disorders affecting 1 to 3 of 1000 newborns. NSHI (nonsyndromic hearing impairment) is observed in about 70% of cases with a genetic background and is mostly caused by autosomal recessive mutations. Mutations in GJB2 gene, encoding gap junction beta 2 protein (connexin 26) are found in 50% Caucasians with profound NSHI. 35delG is the most frequent GJB2 mutation leading to NSHI in European populations, especially of Mediterranean descent, with carrier frequency up to 1/30. The aim of this study was to determine the allelic frequency of 35delG mutation in patients with NSHI and in normal hearing individuals in the Croatian population. The method we used is based on the principle of PCR-mediated site-directed mutagenesis, followed by a BsiYI digestion. PCR products were subsequently size-separated by electrophoresis on a 4% agarose gel and analyzed. Results: we analyzed 29 unrelated individuals with nonsyndromic sensory deafness and 342...

PubMed, Jun 13, 2024

Aim: To determine the spectrum and frequency of disease-causing variants in patients with non-syn... more Aim: To determine the spectrum and frequency of disease-causing variants in patients with non-syndromic hearing loss (NSHL) and to investigate the diagnostic yield of the applied genetic methods. Methods: The study enrolled 306 unrelated patients with childhood-onset, mild-to-profound NSHL referred to Children's Hospital Zagreb for genetic testing between March 2006 and October 2023. The GJB2 variants were analyzed with the multiplex ligation-dependent probe amplification method and Sanger sequencing of the coding region of the GJB2 gene. In 21 patients negative for GJB2 biallelic variants, clinical exome sequencing (CES) was performed. Results: Among 234 disease-associated GJB2 alleles detected, 19 were clinically relevant, of which 18 were reported as pathogenic/likely pathogenic. The c.35delG variant accounted for 73.5% of the mutated alleles. More than half of the patients with biallelic GJB2 variants (64/110, 58.2%) were 35delG homozygotes. Seventeen non-GJB2 variants were found in 10 genes (TECTA, NOG, SLC26A4, PCDH15, TMPRSS3, USH2A, GATA3, MYO15A, SOX10, COL2A1) in 11 participants, and 5 variants (in TECTA, NOG, PCDH15, and SOX10) were novel (29.4%). Conclusion: We were able to elucidate the genetic cause of hearing loss in 121 patients, with an overall diagnostic rate of 39.5%. The c.35delG was the most common variant. CES allowed us to diagnose almost half of the patients with HL; to distinguish NSHL from the syndromic form of HL in cases where the phenotype was unclear or where symptoms were absent from an early age; and to discover novel variants.

PubMed, Oct 30, 2023

Missense variants in the α-tectorin gene (TECTA) cause autosomal dominant (DFNA8/A12) non-syndrom... more Missense variants in the α-tectorin gene (TECTA) cause autosomal dominant (DFNA8/A12) non-syndromic hearing loss (ADNSHL) and account for a considerable number of ADNSHL cases. According to genotype-phenotype correlation studies, missense variants in the zona pellucida (ZP) domain of α-tectorin predominantly cause mid-frequency HL. Here, we report on clinical exome sequencing results in a large family with early-onset, sensorineural, moderate-to-severe mid-frequency HL. We identified one heterozygous c.6183G>T variant near the ZP domain of TECTA segregating in five family members. This variant was previously reported as a variant of uncertain significance in a family with ADNSHL. On the basis of specific segregation in the currently studied family and the general guidelines of the American College of Medical Genetics and Genomics, we argue that the TECTA c.6183G>T variant should be considered a likely pathogenic cause of ADNSHL. This report adds to the knowledge on the rare c.6183G>T missense variant, which affects the immediate vicinity of the ZP domain in TECTA. Our findings highlight the importance of clinical evaluation in patients with familial HL and of studying family segregation when assessing the pathogenicity of a variant.

Croatian Medical Journal, Sep 30, 2023

The first case report of distal 16p12.1p11.2 trisomy and proximal 16p11.2 tetrasomy inherited fro... more The first case report of distal 16p12.1p11.2 trisomy and proximal 16p11.2 tetrasomy inherited from both parents CASE REPORT

Croatian Medical Journal, Sep 30, 2023

Missense variants in the α-tectorin gene (TECTA) cause autosomal dominant (DFNA8/A12) non-syndrom... more Missense variants in the α-tectorin gene (TECTA) cause autosomal dominant (DFNA8/A12) non-syndromic hearing loss (ADNSHL) and account for a considerable number of ADNSHL cases. According to genotype-phenotype correlation studies, missense variants in the zona pellucida (ZP) domain of α-tectorin predominantly cause mid-frequency HL. Here, we report on clinical exome sequencing results in a large family with early-onset, sensorineural, moderate-to-severe mid-frequency HL. We identified one heterozygous c.6183G>T variant near the ZP domain of TECTA segregating in five family members. This variant was previously reported as a variant of uncertain significance in a family with ADNSHL. On the basis of specific segregation in the currently studied family and the general guidelines of the American College of Medical Genetics and Genomics, we argue that the TECTA c.6183G>T variant should be considered a likely pathogenic cause of ADNSHL. This report adds to the knowledge on the rare c.6183G>T missense variant, which affects the immediate vicinity of the ZP domain in TECTA. Our findings highlight the importance of clinical evaluation in patients with familial HL and of studying family segregation when assessing the pathogenicity of a variant.

Paediatria Croatica, 2004

Dicentrics are chromosomes with two centromeres. This structurally aberrant chromosomes are highl... more Dicentrics are chromosomes with two centromeres. This structurally aberrant chromosomes are highly unstable, and rare constant member of the human karyotype. On the other hand, stable dicentrics usually present one active and one inactivate centromere and behave like monocentrics. The investigation conducted so far disclosed several types and different mechanisms of origin of dicentric chromosomes. In this report we present the results of cytogenetic and molecular study in a 5-years old girl with mild dismorphism, growth retardation, behavioral problems and structural rearrangement of X chromosome. Cytogenetic analysis was performed on short-term lymphocyte cultures of the proband and her parents. Chromosomes were GTG and CBG banded, while X chromosome inactivation was studied using RBG method. Fluorescence in situ hybridisation (FISH) was carried out on patients metaphase chromosomes and interphase cells with X chromosome painting and centromeric probes. The parental origin of aberrant chromosome was investigated by DNA polymorphisms analysis. Barr body analysis was performed on buccal mucosa smears stained by routine acetic orcein. Both parents presented normal karyotype. Leukocyte chromosome analyisis of the proband revealed one normal and one aberrant X chromosome. The rearranged X is a large submetacentric with one primary constriction and two blocks of C-staining. FISH analysis revealed that aberrant chromosome is composed entirely of the X chromosome material. Interphase FISH with alpha satellite X centromere probe revealed two mosaic cell lines. Three signals were observed in 84.5%, and one signal in 15.5% of interphase cells. Replication analysis showed that the normal X always early replicates, while the dicentric was late replicating in all investigated cells. The buccal smear revealed X-chromosome positive cells, and in some cells the Barr body was bipartite. Molecular analysis of DNA polymorphisms indicates that the dicentric is of paternal origin. Based on this study the karyotype of the patients is 45, X/46, X, psu idic(X)(q22.3), with the trisomy Xpter-q22.3 and monosomy Xqter-q22.3. We suggest that dicentric X is the result of isolocal break in the two chromatides of the paternal X chromosome, subsequent rejoining of broken ends, followed by inactivation of one centromere.

Fenomen odbijanja cijepljenja nazivamo antivakcinacijskim stavom, a širenje antivakcinacijskim po... more Fenomen odbijanja cijepljenja nazivamo antivakcinacijskim stavom, a širenje antivakcinacijskim pokretom ili kampanjom. Pritom oni koji odbijaju cijepljenje zapravo ne razumiju motive onih koji ih od cijepljenja odgovaraju, ali se brane da to rade zato jer sumnjaju ili ne razumiju argumente onih koji ih na cijepljenje nagovaraju. Cijepljenje se odbija iz međusobno logički i stručno suprotstavljenih argumenata. Riječ je o stručnoj shizmi u kojoj nema oblikovane ni transparente osnove, već se homogenizacija protiv cijepljenja zasniva na mnogo različitih i često suprotstavljenih kritika/negacija cjepiva, cijepljenja, struke, establišmenta, zakonske regulative, biznisa i farmaceutske industrije. Antivakcinacijski pokret došao je i do Hrvatske. U nascentnoj situaciji trebalo bi zaštititi cjepitelje od materijalne ili kaznene odgovornosti za još i sad obveznu preventivnu mjeru, te hitnim i razgovijetnim mjerama edukacije i javne promidžbe osigurati održanje adekvatnog obuhvata za postojeća cjepiva iz obveznog programa. Uz to treba osnovati odštetni fond za nuspojave cijepljenja. Umjesto sankcije za odbijanje cijepljenja treba uvesti obvezu posebnog dopunskog osiguranja za rizik svake bolesti za koju roditelj odbije cijepiti svoje dijete. U današnjoj situaciji prikladni odgovor bio bi i uvođenje novog cjepiva u program univerzalnog cijepljenja (npr. cijepljenje protiv rotavirusa ili pneumokokne bolesti).

European journal of medical genetics, Jan 16, 2018

Beckwith Wiedemann syndrome is a complex developmental disorder characterized by somatic overgrow... more Beckwith Wiedemann syndrome is a complex developmental disorder characterized by somatic overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycemia, and predisposition to embryonal tumors. We present epidemiological and clinical aspects of patients with Beckwith Wiedemann syndrome diagnosed prenatally or in the early years of life, using data from EUROCAT (European Surveillance of Congenital Anomalies) registries. The study population consisted of 371 cases identified between January 1990 and December 2015 in 34 registries from 16 European countries. There were 15 (4.0%) terminations of pregnancy after prenatal detection of severe anomaly/anomalies, 10 fetal deaths (2.7%), and 346 (93.3%) live-births. Twelve (3.6%) of the 330 live-births with available information on survival died in the first week of life, of those eleven (91.6%) were preterm. First-year survival rate was 90.9%. Prematurity was present in 40.6% of males and 33.9% of females. Macrosomia was found in 49....

World Journal of Pediatric Surgery

ObjectiveUndescended testes (UDT) is the most common anomaly of the male genitourinary tract. The... more ObjectiveUndescended testes (UDT) is the most common anomaly of the male genitourinary tract. The guidelines suggest that orchidopexy in congenitally UDT should be performed between 6 months and 18 months of age, while in acquired UDT, orchidopexy should be performed before puberty. Delay in treatment increases the risk of cancer and infertility. The main aim of this study was to determine whether we meet international standards in the treatment of UDT.MethodsThe present study included all boys who underwent orchidopexy either due to congenital or acquired UDT in 2019 (from January 1 to December 31). For each group, laterality, location, associated anomalies, premature birth and in how many cases ultrasound was applied were determined. Additionally, for each group, the types of surgery, the number of necessary reoperations, and in how many cases atrophy occurred were determined. Finally, ages of referral, of clinical examination, and of orchidopexy were determined.ResultsDuring this...

American Journal of Medical Genetics, 2004

We report a 19-year-old woman with minor craniofacial anomalies, mild mental retardation, and for... more We report a 19-year-old woman with minor craniofacial anomalies, mild mental retardation, and foramina parietalia permagna (FPP) (OMIM 168500). Cytogenetic analysis showed a de novo interstitial chromosome 22 long arm duplication. FISH with a panel of chromosome 22q12-q13 bands-specific BAC clones refined the cytogenetic investigation, and restricted the duplicated segment to the q12 region. Mutation analysis of FPP genes identified an insertion mutation in the ALX4 gene (344insC) in the proband and her father with loss of function of the gene. The patient's phenotype is considered in the light of the results of the cytogenetic, FISH, and molecular investigations, and her features are compared with those of other patients with similar duplications. Finally, variable phenotypic findings due to different 22q duplicated chromosomal segments are discussed. Our report indicates that 22q12 interstitial duplications are associated with craniofacial anomalies and mild mental retardation, while life threatening malformations are usually not present. Although these phenotypic changes are common and non-specific, molecular study of our patient established more precise relationships between clinical findings and 22q duplicated region(s). This approach fosters better counseling of the families of patients with newly diagnosed, similar duplications.

9. hrvatski biološki kongres s međunarodnim sudjelovanjem, 2006

Paediatria Croatica, 2004

Trisomija kratkog kraka kromosoma 12 rijetka je pojava u humanoj patologiji s ucestaloscu od 1 : ... more Trisomija kratkog kraka kromosoma 12 rijetka je pojava u humanoj patologiji s ucestaloscu od 1 : 50.000 novorođenih. U ovom radu prikazujemo djevojcicu u dobi od 2 godine i 11 mjeseci primljenu na geneticku obradu zbog dismorfije i razvojnog zaostajanja. Analizom prometafaznih kromosoma bolesnice određen je kariotip: 46, XX, der(5), t(5 ; 12)(5p15.3 ; 12p12.2)mat. Molekularna ispitivanja mikrosatelitnim markerima u podrucju mjesta loma potvrdila su trisomiju kratkog kraka kromosoma 12 u regiji 12p12.2, dok je mjesto loma kratkoga kraka kromosoma 5 u regiji 5p15.33 uputilo na terminalnu delecije manju od 3.1 Mb, smjestenu distalno od kriticnog segmenta za fenotip cri du chat. Premda je bolesnica imala fenotipska obilježja kako parcijanle trisomije 12p, tako i monosomije 5p, molekularna analiza je uputila na to da je kod djevojcice rijec o cistoj trisomiji 12p12.2 koja je klinicki vrlo nalik na fenotip cri du chat.

Etiologija slusnog ostecenja vrlo je raznolika. Vanjski cimbenici uzrokom su oko 40% slusnih oste... more Etiologija slusnog ostecenja vrlo je raznolika. Vanjski cimbenici uzrokom su oko 40% slusnih ostecenja, dok je oko 60% ostecenja sluha uzrokovano genetickim cimbenicima. Oko 20-50% nasljedne nesindromske zamjedbene gluhoce uzrokovano je mutacijama u genima GJB2 i GJB6. Zastupljenost pojedinih mutacija pokazuje regionalne razlike. Cilj: 1) provesti prospektivno istraživanje etiologije slusnog ostecenja u grupi osoba trajnim ostecenjem sluha obrađenih u Ambulanti za klinicku genetiku 2) utvrditi ucestalost mutacija gena GJB2 i GJB6 u populaciji hrvatskih bolesnika sa NSHL 3) predložiti optimalan model organizacije infrastrukture i nacina obrade prirođenog slusnog ostecenja kod djece dijagnosticirane putem sveobuhvatnog novorođenackog probira u Hrvatskoj. Rezultati: tijekom 2003. godine obradili smo 148 djece s ostecenjem sluha, 36 s provodnom nagluhosti, 92 sa zamjedbenom, te 20 s mijesanom nagluhosti. U 14 (9, 6%) utvrđeni su vanjski cimbenici kao najvjerojatniji uzrok slusnog ostece...

Monosomija 18p je jedna od najcescih delecija autosoma. Klinicko pojavljivanje 18p je veoma varij... more Monosomija 18p je jedna od najcescih delecija autosoma. Klinicko pojavljivanje 18p je veoma varijabilno. U vecini opisanih bolesnika monosomija je posljedica terminalne delecije, dok je u relativno malom broju slucajeva rezultat de novo translokacije. Nebalansirana translokacija citavog kraka kromosoma 18 obicno zahvaca akrocentricne kromosome 21 i 22. Mehanizam nastanka kromosomskog poremecaja nije jasan i predmet je znanstvenog interesa. U ovom radu prikazujemo rezultate klinickih i citogenetickih ispitivanja u djevojcice s parcijalnom monosomijom 18p. Nasa pacijentica je 8 godina stara djevojcica s mentalnom retardacijom i dismorfijom. Citogenetska analiza je izvrsena na preparatima dobivenim kratkotrajnom kulturom stanica periferne krvi. Koristili smo GTG-metodu identifikacije prometafaznih kromosoma i FISH metodu s pomocu specificnih probi za identifikaciju kromosoma 15 i 18. ToTelVysion Multi-color DNA Probe Mixtures za analizu subtelomernih regija i probe Prader Willi/Angelma...

Paediatria Croatica, 2007

Hearing loss is one of the most common congenital disorders affecting 1 to 3 of 1000 newborns. NS... more Hearing loss is one of the most common congenital disorders affecting 1 to 3 of 1000 newborns. NSHI (nonsyndromic hearing impairment) is observed in about 70% of cases with a genetic background and is mostly caused by autosomal recessive mutations. Mutations in GJB2 gene, encoding gap junction beta 2 protein (connexin 26) are found in 50% Caucasians with profound NSHI. 35delG is the most frequent GJB2 mutation leading to NSHI in European populations, especially of Mediterranean descent, with carrier frequency up to 1/30. The aim of this study was to determine the allelic frequency of 35delG mutation in patients with NSHI and in normal hearing individuals in the Croatian population. The method we used is based on the principle of PCR-mediated site-directed mutagenesis, followed by a BsiYI digestion. PCR products were subsequently size-separated by electrophoresis on a 4% agarose gel and analyzed. Results: we analyzed 29 unrelated individuals with nonsyndromic sensory deafness and 342...