Premium
Expanding the phenotype of cerebellar‐facial‐dental syndrome: Two siblings with a novel variant in BRF1
Author(s) -
Valenzuela Irene,
Codina Marta,
FernándezÁlvarez Paula,
Mur Pilar,
Valle Laura,
Tizzano Eduardo F.,
Cuscó Ivon
Publication year - 2020
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61839
Subject(s) - microcephaly , missense mutation , short stature , cerebellar hypoplasia (non human) , hypoplasia , intellectual disability , corpus callosum , sensorineural hearing loss , medicine , global developmental delay , exome sequencing , phenotype , pediatrics , hearing loss , cerebellum , genetics , audiology , pathology , biology , gene
Abstract Cerebellofaciodental syndrome (MIM #616202) is an autosomal recessive condition characterized by intellectual disability, microcephaly, cerebellar hypoplasia, dysmorphic features, and short stature. To date, eight patients carrying biallelic BRF1 variants have been reported. Here, we describe two siblings with congenital microcephaly and corpus callosum hypoplasia, pre and postnatal growth retardation, congenital heart defect and severe global developmental delay. We also detected additional findings not previously reported in this syndrome, including bilateral sensorineural hearing impairment and inner ear malformation. Whole exome sequencing identified a novel homozygous missense variant (c.654G>C, p.[Trp218Cys]) in BRF1 , predicted to affect the protein structure. Expression assessment showed extremely low BRF1 protein expression caused by the identified variant, supporting its causal involvement. The description of new patients with cerebellofaciodental syndrome is essential to better delineate the phenotypic and genotypic spectrum of the disease.