SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations.
Sensorineural hearing loss is the most frequent sensory deficit of childhood and is of genetic origin in up to 75% of cases. It has been shown that mutations of the SLC26A4 (PDS) gene were involved in syndromic deafness characterized by congenital sensorineural hearing impairment and goitre (Pendred's syndrome), as well as in congenital isolated deafness (DFNB4). While the prevalence of SLC26A4 mutations in Pendred's syndrome is clearly established, it remains to be studied in large cohorts of patients with nonsyndromic deafness and detailed clinical informations. In this report, 109 patients from 100 unrelated families, aged from 1 to 32 years (median age: 10 years), with nonsyndromic deafness and enlarged vestibular aqueduct, were genotyped for SLC26A4 using DHPLC molecular screening and sequencing. In all, 91 allelic variants were observed in 100 unrelated families, of which 19 have never been reported. The prevalence of SLC26A4 mutations was 40% (40/100), with biallelic mutation in 24% (24/100), while six families were homozygous. All patients included in this series had documented deafness, associated with EVA and without any evidence of syndromic disease. Among patients with SLC26A4 biallelic mutations, deafness was more severe, fluctuated more than in patients with no mutation. In conclusion, the incidence of SLC26A4 mutations is high in patients with isolated deafness and enlarged vestibular aqueduct and could represent up to 4% of nonsyndromic hearing impairment. SLC26A4 could be the second most frequent gene implicated in nonsyndromic deafness after GJB2, in this Caucasian population.
Service d'ORL et de Chirurgie Cervico-faciale, Hôpital d'Enfants Armand-Trousseau, AP-HP, Paris, France.
Sébastien
S
Albert
Hélène
H
Blons
Laurence
L
Jonard
Delphine
D
Feldmann
Pierre
P
Chauvin
Nathalie
N
Loundon
Annie
A
Sergent-Allaoui
Muriel
M
Houang
Alain
A
Joannard
Sébastien
S
Schmerber
Bruno
B
Delobel
Jacques
J
Leman
Hubert
H
Journel
Hélène
H
Catros
Hélène
H
Dollfus
Marie-Madeleine
MM
Eliot
Albert
A
David
Catherine
C
Calais
Valérie
V
Drouin-Garraud
Marie-Françoise
MF
Obstoy
Patrice
P
Tran Ba Huy
Didier
D
Lacombe
Françoise
F
Duriez
Christine
C
Francannet
Pierre
P
Bitoun
Christine
C
Petit
Eréa-Noël
EN
Garabédian
Rémy
R
Couderc
Sandrine
S
Marlin
Françoise
F
Denoyelle
D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D003638:Deafness / Q000151:congenital / Q000235:genetics / Q000473:pathology; D005260:Female; D006042:Goiter / Q000235:genetics / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000473:pathology; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D015995:Prevalence; D000076988:Sulfate Transporters; D013577:Syndrome; D014723:Vestibular Aqueduct / Q000002:abnormalities*; D044465:White People
D017630:Connexins; C000607042:GJB2 protein, human; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26