First identified Korean family with Tatton-Brown-Rahman Syndrome caused by the novelvariant c.118G>C p.(Glu40Gln)

Annals of Pediatric Endocrinology & Metabolism

Ji-Young Seo¹  Cha Gon Lee¹  Ja-Hyun Jang² 

[1] Department of Pediatrics, Nowon Eulji Medical Center, Eulji University, Seoul, Korea;GC Genome, Yongin, Korea;

关键词: germ-line mutation;    tatton-brown-rahman syndrome;    growth disorder;    intellectual disability;    high throughput nucleotide sequencing;    dna sequence analysis;   

DOI  :  10.6065/apem.2019.24.4.253

来源: DOAJ

【 摘 要 】

Tatton-Brown-Rahman Syndrome (TBRS), an overgrowth syndrome caused by heterozygous mutation of DNMT3A, first was described in 2014. Approximately 60 DNMT3A variants, including 32 missense variants, have been reported, with most missense mutations located on the DNMT3A functional domains. Autosomal dominant inheritance by germ-line mutation of DNMT3A has been reported, but vertical transmission within a family is extremely rare. Herein, we report the first Korean family with maternally inherited TBRS due to the novel heterozygous DNMT3A variant c.118G>C p.(Glu40Gln), located outside the main functional domain and identified by multigene panel sequencing. The patient and her mother had typical clinical features, including tall stature during childhood, macrocephaly, intellectual disability, and characteristic facial appearance. TBRS shows milder dysmorphic features than other overgrowth syndromes, potentially leading to underdiagnosis and underestimated prevalence; thus, targeted multigene panel sequencing including DNMT3A will be a useful tool in cases of overgrowth and unexplained mild intellectual disability for early diagnosis and genetic counseling.

【 授权许可】

Unknown