Molecular and clinical analyses of two patients with UPD(16)mat detected by screening 94 patients with Silver-Russell syndrome phenotype of unknown aetiology

Takanobu Inoue, Hideaki Yagasaki, Junko Nishioka, Akie Nakamura, Keiko Matsubara, Satoshi Narumi, Kazuhiko Nakabayashi, Kazuki Yamazawa, Tomoko Fuke, Akira Oka, Tsutomu Ogata, Maki Fukami, Masayo Kagami

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22 Citations (Scopus)

Abstract

background recently, 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. Objective to clarify the prevalence of UpD(16)mat in aetiology-unknown patients with SrS phenotype and phenotypic differences between UpD(16)mat and SrS. Methods We 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. results We 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. Conclusion We suggest considering genetic testing for UpD(16)mat in SrS phenotypic patients without known aetiology.

Original languageEnglish
Pages (from-to)413-418
Number of pages6
JournalJournal of medical genetics
Volume56
Issue number6
DOIs
Publication statusPublished - 2019
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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