GJB2 mutation spectrum in 209 hearing impaired individuals of predominantly Caribbean Hispanic and African descent.

OBJECTIVE: The purpose of the study is to determine whether Caribbean Hispanic and African admixture populations have a paucity of mutations in GJB2, encoding connexin 26. METHODS: We reported the paucity of mutations in GJB2 and deletions in GJB6 in Caribbean Hispanic and African admixture populations in the Bronx, NY, in 2007 [1]. We have now collected 102 additional probands with non-syndromic sensorineural hearing impairment (NSHI), for a total of 209. We describe here a presentation of the combined data. RESULTS: Of the 209 probands, 36% have affected family members with NSHI and the rest have sporadic occurrence. Of the familial cases, 43% had a first-degree relative affected, and the remainder a more distant relative. The hearing impairment ranged from unilateral mild to bilateral profound, with 76% exhibiting bilateral NSHI (BLNSHI). The single coding exon of the GJB2 gene was sequenced in 209 probands, PCR screening for del(GJB6-D13S1830) and sequencing of the non-coding exon of GJB2 to look for the known splice site mutation was performed in 32 NSHI patients with a heterozygous variation in GJB2, and multiplex ligation-dependent probe amplification (MLPA) testing of GJB2 and GJB6 exon deletions or amplifications (P163 GJB-WFS1 kit) was done in 70 probands. Eight unrelated individuals had biallelic GJB2 mutations, representing 4% of our entire cohort, or 5% of our probands with BLNSHI. Of 127 probands of Hispanic or African descent with BLNSHI, six (4.7%) had biallelic pathogenic mutations, three (2.3%) had monoallelic mutations and 118 (93%) had no disease-causing mutations in GJB2. At the same time, no major deletions were identified either by PCR screening (del(GJB6-D13S1830)) or by MLPA analysis (GJB2 or GJB6), and no subjects had the known splice site mutation in GJB2. CONCLUSION: These results demonstrate that GJB2 is not the major contributor to the genetic basis of NSHI for the Bronx minority admixture populations.

Genetic evaluation of American minority pediatric cochlear implant recipients.

OBJECTIVE: To review the results of genetic evaluation of American minority pediatric cochlear implant recipients over a 5-year period. METHODS: Case series review of pediatric cochlear implant recipients of Caribbean Hispanic and African American admixture descent with severe to profound sensorineural hearing loss at a tertiary care children's hospital. RESULTS: Out of 28 patients receiving cochlear implants, 14 were of Caribbean Hispanic or African American admixture ancestry. Six (43%) had environmental risk factors for sensorineural hearing loss. Eight (57%) patients had presumed genetic sensorineural hearing loss; two of whom were syndromic and six non-syndromic. Patients with no clear etiology for hearing loss were tested for Gap Junction Beta 2 (GJB2) mutations. Within this admixture group, we found no biallelic mutations in GJB2, while two patients, both with environmental risk factors for sensorineural hearing loss, had monoallelic GJB2 variants. One patient of mixed ethnicity (Caribbean Hispanic, Turkish, Macedonian), not included as part of the 14, had the common Caucasian founder mutation, 35delG, along with a heterozygous polymorphism in the GJB2 gene. This extends previous data showing a paucity of GJB2 mutations in these admixture populations. CONCLUSIONS: We found no biallelic GJB2 mutations in our admixture cochlear implant population, and two sequence variants of the gene, only one of which was disease causing. This suggests that the incidence of GJB2 mutations in these admixture populations is low. Hence, there may be low cost-benefit of GJB2 mutation analysis in these admixture populations with severe to profound non-syndromic sensorineural hearing loss.