A Novel Loss-of-Function Mutation in HOXB1 Associated with Autosomal Recessive Hereditary Congenital Facial Palsy in a Large Iranian Family

<jats:p>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 &lt;i&gt;HOXB1&lt;/i&gt; 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 &lt;i&gt;HOXB1&lt;/i&gt; 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 &lt;i&gt;HOXB1&lt;/i&gt; 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.</jats:p>