Exome sequencing reveals a novel splice site variant in HUWE1 gene in patients with suspected Say-Meyer Syndrome
| Autor: | Salah Basheer, Akhilesh Pandey, Satish Chandra Girimaji, Deepshikha Chandel, Somasekar Seshagiri, Babylakshmi Muthusamy, Srimonta Gayen, Lakshmi Dhevi N. Selvan, Thong T. Nguyen, Aravind K. Bandari, Jesna Manoj |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Adolescent Autism Spectrum Disorder Ubiquitin-Protein Ligases Trigonocephaly 030105 genetics & heredity Gene mutation Biology Article Craniofacial Abnormalities 03 medical and health sciences Hypotelorism Intellectual Disability Exome Sequencing Genetics medicine Humans Protein Isoforms splice Abnormalities Multiple Exome Child Genetics (clinical) Exome sequencing Growth Disorders Molecular Reproduction Development & Genetics Comparative Genomic Hybridization Tumor Suppressor Proteins Cytogenetics General Medicine Cranial Sutures medicine.disease 030104 developmental biology Child Preschool Say–Meyer syndrome Female RNA Splice Sites Comparative genomic hybridization |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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