TY - JOUR
T1 - Exome sequencing reveals a novel splice site variant in HUWE1 gene in patients with suspected Say-Meyer syndrome
AU - Muthusamy, Babylakshmi
AU - Nguyen, Thong T.
AU - Bandari, Aravind K.
AU - Basheer, Salah
AU - Selvan, Lakshmi Dhevi N.
AU - Chandel, Deepshikha
AU - Manoj, Jesna
AU - Gayen, Srimonta
AU - Seshagiri, Somasekar
AU - Chandra Girimaji, Satish
AU - Pandey, Akhilesh
N1 - Publisher Copyright:
© 2019 The Authors
PY - 2020/1
Y1 - 2020/1
N2 - 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.
AB - 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.
KW - Calvarial sutures
KW - Cranial sutures
KW - Craniosynostosis
KW - Developmental delay
KW - Metopic suture
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U2 - 10.1016/j.ejmg.2019.02.007
DO - 10.1016/j.ejmg.2019.02.007
M3 - Article
C2 - 30797980
AN - SCOPUS:85062230803
SN - 1769-7212
VL - 63
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
IS - 1
M1 - 103635
ER -