Molecular and clinical analyses of two patients with UPD(16)mat detected by screening 94 patients with Silver-Russell syndrome phenotype of unknown aetiology
| Autor: | Tsutomu Ogata, Tomoko Fuke, Junko Nishioka, Masayo Kagami, Kazuki Yamazawa, Takanobu Inoue, Hideaki Yagasaki, Satoshi Narumi, Maki Fukami, Keiko Matsubara, Akira Oka, Akie Nakamura, Kazuhiko Nakabayashi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Pathology medicine.medical_specialty Adolescent 030105 genetics & heredity Gene mutation 03 medical and health sciences Young Adult maternal uniparental disomy of chromosome 16 Chromosome 16 parasitic diseases Genetics medicine Humans Genetic Predisposition to Disease Child Exome Genetics (clinical) Genetic Association Studies Genetic testing medicine.diagnostic_test business.industry Silver–Russell syndrome Infant znf597 silver-russell syndrome DNA Methylation Uniparental Disomy medicine.disease Phenotype 030104 developmental biology Hypospadias Child Preschool netchine-harbison clinical scoring system Female Epigenetics business Chromosomes Human Pair 16 SNP array Transcription Factors |
| Zdroj: | Journal of Medical Genetics |
| ISSN: | 1468-6244 |
| Popis: | BackgroundRecently, a patient with maternal uniparental disomy of chromosome 16 (UPD(16)mat) presenting with Silver-Russell syndrome (SRS) phenotype was reported. SRS is characterised by growth failure and dysmorphic features.ObjectiveTo clarify the prevalence of UPD(16)mat in aetiology-unknown patients with SRS phenotype and phenotypic differences between UPD(16)mat and SRS.MethodsWe studied 94 patients with SRS phenotype of unknown aetiology. Sixty-three satisfied the Netchine-Harbison clinical scoring system (NH-CSS) criteria, and 25 out of 63 patients showed both protruding forehead and relative macrocephaly (clinical SRS). The remaining 31 patients met only three NH-CSS criteria, but were clinically suspected as having SRS. To detect UPD(16)mat, we performed methylation analysis for the ZNF597:TSS-differentially methylated region (DMR) on chromosome 16 and subsequently performed microsatellite, SNP array and exome analyses in the patients with hypomethylated ZNF597:TSS-DMR.ResultsWe identified two patients (2.1%) with a mixture of maternal isodisomy and heterodisomy of chromosome 16 in 94 aetiology-unknown patients with SRS phenotype. Both patients exhibited preterm birth and prenatal and postnatal growth failure. The male patient had ventricular septal defect and hypospadias. Whole-exome sequencing detected no gene mutations related to their phenotypes.ConclusionWe suggest considering genetic testing for UPD(16)mat in SRS phenotypic patients without known aetiology. |
| Databáze: | OpenAIRE |
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