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

Muthusamy, B and Nguyen, TT and Bandari, AK and Basheer, S and Selvan, LDN and Chandel, D and Manoj, J and Gayen, S and Seshagiri, S and Chandra Girimaji, S and Pandey, A (2019) Exome sequencing reveals a novel splice site variant in HUWE1 gene in patients with suspected Say-Meyer syndrome. In: European Journal of Medical Genetics .

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Official URL: https://doi.org/10.1016/j.ejmg.2019.02.007


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. © 2019 The Authors

Item Type: Journal Article
Publication: European Journal of Medical Genetics
Additional Information: Copyright for this article belongs to Elsevier.
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited: 09 Apr 2019 05:24
Last Modified: 09 Apr 2019 05:24
URI: http://eprints.iisc.ac.in/id/eprint/62042

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