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

Babylakshmi Muthusamy, Thong T. Nguyen, Aravind K. Bandari, Salah Basheer, Lakshmi Dhevi N. Selvan, Deepshikha Chandel, Jesna Manoj, Srimonta Gayen, Somasekar Seshagiri, Satish Chandra Girimaji, Akhilesh Pandey

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Article number103635
JournalEuropean Journal of Medical Genetics
Issue number1
StatePublished - Jan 2020


  • Calvarial sutures
  • Cranial sutures
  • Craniosynostosis
  • Developmental delay
  • Metopic suture

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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