Brown-Vialetto-Van Laere syndrome, a ponto-bulbar palsy with deafness, is caused by mutations in c20orf54

Abstract

Brown-Vialetto-Van Laere syndrome is a rare neurological disorder with a variable age at onset and clinical course. The key features are progressive ponto-bulbar palsy and bilateral sensorineural deafness. A complex neurological phenotype with a mixed picture of upper and lower motor neuron involvement reminiscent of amyotrophic lateral sclerosis evolves with disease progression. We identified a candidate gene, C20orf54, by studying a consanguineous family with multiple affected individuals and subsequently demonstrated that mutations in this gene were the cause of disease in other, unrelated families.

Figure 1

Multiple Alignment of C20orf54 Protein Sequence The C20orf54 protein sequence with the six missense mutations (p.E36K, p.R132W, p.F224L, p.L350M, p.V413A, and p.F457L) is shown in eight orthologs. The mutations p.E36K and p.V413A are found in case 9 (Table 1), who is a compound heterozygote. The alignment was performed with ClustalW2, and the GenBank accession numbers are NP_212134.3, XP_001152229.1, XP_001112427.1, XP_542938.2, XP_001916183.1, NP_001032275.1, NP_081448.2, and NP_001033515.