Sequence variants of the DFNB31 gene among Usher syndrome patients of diverse origin.
OBJECTIVE
It has been demonstrated that mutations in deafness, autosomal recessive 31 (DFNB31), the gene encoding whirlin, is responsible for nonsyndromic hearing loss (NSHL; DFNB31) and Usher syndrome type II (USH2D). We screened DFNB31 in a large cohort of patients with different clinical subtypes of Usher syndrome (USH) to determine the prevalence of DFNB31 mutations among USH patients.


METHODS
DFNB31 was screened in 149 USH2, 29 USH1, six atypical USH, and 11 unclassified USH patients from diverse ethnic backgrounds. Mutation detection was performed by direct sequencing of all coding exons.


RESULTS
We identified 38 different variants among 195 patients. Most variants were clearly polymorphic, but at least two out of the 15 nonsynonymous variants (p.R350W and p.R882S) are predicted to impair whirlin structure and function, suggesting eventual pathogenicity. No putatively pathogenic mutation was found in the second allele of patients with these mutations.


CONCLUSIONS
DFNB31 is not a major cause of USH.
Aller
Elena
E
Unidad de Genética, Hospital Universitario La Fe, Valencia, Spain.
Jaijo
Teresa
T
van Wijk
Erwin
E
Ebermann
Inga
I
Kersten
Ferry
F
García-García
Gema
G
Voesenek
Krysta
K
Aparisi
María José
MJ
Hoefsloot
Lies
L
Cremers
Cor
C
Díaz-Llopis
Manuel
M
Pennings
Ronald
R
Bolz
Hanno J
HJ
Kremer
Hannie
H
Millán
José M
JM
D014644:Genetic Variation; D006801:Humans; D007438:Introns / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D052245:Usher Syndromes / Q000235:genetics*
D008565:Membrane Proteins; C477219:WHRN protein, human