Open AccessA Novel Loss-of-Function Mutation in HOXB1 Associated with Autosomal Recessive Hereditary Congenital Facial Palsy in a Large Iranian Family
Author(s) -
Mohammad Yahya Vahidi Mehrjardi,
Reza Maroofian,
Seyed Mehdi Kalantar,
Mojtaba Jaafarinia,
John K. Chilton,
Mohammadreza Dehghani
Publication year - 2017
Publication title -
molecular syndromology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.609
H-Index - 36
eISSN - 1661-8777
pISSN - 1661-8769
DOI - 10.1159/000477752
Subject(s) - frameshift mutation , missense mutation , sanger sequencing , genetics , nonsense mutation , nonsense , genetic heterogeneity , medicine , mutation , sensorineural hearing loss , hearing loss , phenotype , biology , gene , audiology
Hereditary congenital facial palsy (HCFP) is a rare congenital cranial dysinnervation disorder, recognisable by non-progressive isolated facial nerve palsy (cranial nerve VII). It is caused by developmental abnormalities of the facial nerve nucleus and its nerve. So far, 4 homozygous mutations have been identified in 5 unrelated families (12 patients) with HCFP worldwide. In this study, a large Iranian consanguineous kindred with 5 members affected by HCFP underwent thorough clinical and genetic evaluation. The candidate gene HOXB1 was screened and analysed by Sanger sequencing. As in previous cases, the most remarkable findings in the affected members of the family were mask-like faces, bilateral facial palsy with variable sensorineural hearing loss, and some dysmorphic features. Direct sequencing of the candidate gene HOXB1 identified a novel homozygous frameshift mutation (c.296_302del; p.Y99Wfs*20) which co-segregated with the disease phenotype within the extended family. Our findings expand the mutational spectrum of HOXB1 involved in HCFP and consolidate the role of the gene in the development of autosomal recessive HCFP. Moreover, the truncating mutation identified in this family leads to a broadly similar presentation and severity observed in previous patients with nonsense and missense mutations. This study characterises and defines the phenotypic features of this rare syndrome in a larger family than has previously been reported.