Exome sequencing reveals a novel splice site variant in HUWE1 gene in patients with suspected Say-Meyer syndrome.
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.
['Muthusamy|Babylakshmi|B|', 'Nguyen|Thong T|TT|', 'Bandari|Aravind K|AK|', 'Basheer|Salah|S|', 'Selvan|Lakshmi Dhevi N|LDN|', 'Chandel|Deepshikha|D|', 'Manoj|Jesna|J|', 'Gayen|Srimonta|S|', 'Seshagiri|Somasekar|S|', 'Chandra Girimaji|Satish|S|', 'Pandey|Akhilesh|A|']
D000015:Abnormalities, Multiple D000293:Adolescent D000067877:Autism Spectrum Disorder D002648:Child D002675:Child, Preschool D055028:Comparative Genomic Hybridization D003393:Cranial Sutures D019465:Craniofacial Abnormalities D059472:Exome D005260:Female D006130:Growth Disorders D006801:Humans D008607:Intellectual Disability D008297:Male D020033:Protein Isoforms D022821:RNA Splice Sites D025521:Tumor Suppressor Proteins D044767:Ubiquitin-Protein Ligases D000073359:Whole Exome Sequencing
Developmental delay Calvarial sutures Cranial sutures Craniosynostosis Metopic suture