Exome sequencing reveals a novel splice site variant in HUWE1 gene in patients with suspected Say-Meyer syndrome.

Abstract:

:Say-Meyer syndrome is a rare and clinically heterogeneous syndrome characterized by trigonocephaly, short stature, developmental delay and hypotelorism. Nine patients with this syndrome have been reported thus far although no causative gene has yet been identified. Here, we report two siblings with clinical phenotypes of Say-Meyer syndrome with moderate to severe intellectual disability and autism spectrum disorder. Cytogenetics and array-based comparative genomic hybridization did not reveal any chromosome abnormalities or copy number alterations. Exome sequencing of the patients revealed a novel X-linked recessive splice acceptor site variant c.145-2A > G in intron 5 of HUWE1 gene in both affected siblings. RT-PCR and sequencing revealed the use of an alternate cryptic splice acceptor site downstream, which led to deletion of six nucleotides resulting loss of two amino acids p.(Cys49-Glu50del) in HUWE1 protein. Deletion of these two amino acids, which are located in a highly conserved region, is predicted to be deleterious and quite likely to affect the function of HUWE1 protein. This is the first report of a potential candidate gene mutation for Say-Meyer syndrome, which was initially described four decades ago.

journal_name

Eur J Med Genet

authors

Muthusamy B,Nguyen TT,Bandari AK,Basheer S,Selvan LDN,Chandel D,Manoj J,Gayen S,Seshagiri S,Chandra Girimaji S,Pandey A

doi

10.1016/j.ejmg.2019.02.007

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

103635

issue

1

eissn

1769-7212

issn

1878-0849

pii

S1769-7212(18)30478-6

journal_volume

63

pub_type

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