Two novel compound heterozygous families with a trimutation in the GJB2 gene causing sensorineural hearing loss.

BACKGROUND: Sensorineural hearing loss (SNHL) is a genetically heterogeneous disease. GJB2 gene mutations seem to be the most frequent cause of hereditary hearing impairment in several populations. There is variability in the mutations in the GJB2 gene worldwide; this remarks the influence of ethnic background in SNHL. OBJECTIVE: To describe the presence of two trimutations in the GJB2 gene in two Mexican families with hereditary SNHL. MATERIALS AND METHODS: Two unrelated Mexican families with prelingual SNHL were included in the study. Analysis of the GJB2 gene through PCR and DNA direct sequencing analysis was performed in all members of the families and in 100 normal controls. RESULTS: Affected member of the family 1 showed the trimutation p.S19R/p.R32S/p.E47*, whereas affected members of the family 2 showed the trimutation p.F31I/p.W44*/p.V84M. Parents of both families were heterozygous with normal audition. CONCLUSION: We found a novel mutation in the GJB2 gene and two trimutations with SNHL not previously reported. This remarks the complexity in the pattern of mutations in the GJB2 gene in SNHL and enriches the spectrum of the type of molecular defects in the GJB2 gene.

ADRB1 and ADBR2 gene polymorphisms and the ocular hypotensive response to topical betaxolol in healthy Mexican subjects.

BACKGROUND: The ß adrenergic receptors (ADRB) are expressed in the ciliary body and trabecular meshwork, structures involved in aqueous humor production and outflow, respectively. ADRB are members of the adrenergic family of G-protein-coupled receptors. Topic ß blockers have a good local and systemic tolerance; they reduce the aqueous humor production and eye strain blocking the ADRB of the ciliary body and interfering with adenylate cyclase. However, the ocular hypotensive response is not the same in all patients and could be mediated by the polymorphisms of the ADRB genes. MATERIALS AND METHODS: Seventy-two healthy subjects were studied after treatment with topical betaxolol in both eyes. We analyzed ADRB1 and ADRB2 gene polymorphisms by PCR and automated DNA sequencing. RESULTS: There was statistically significant difference between baseline intraocular pressure (IOP) and final IOP of both eyes (baseline IOP 16.2 ± 1.2 - follow-up IOP 13.6 ± 2.0 (mean difference-2.5 ± 1.3, p < 0.001). Gly389 had a higher baseline IOP than Arg389 (17.0 ± 1.2 mmHg versus 16.0 ± 1.2 mmHg; p = 0.02), and conversely Arg389 had a greater magnitude of response than Gly389 to betaxolol therapy (-2.9 ± 1.1 mmHg versus -0.7 ± 0.4 mmHg; p < 0.001). Gln27 had a higher response than Glu27 (-2.7 ± 1.3 mmHg versus -1.9 ± 1.0; p = 0.02). CONCLUSION: Arg389 polymorphism of the ADRB1 gene and Gln27 polymorphism of the ADRB2 gene were associated with the hypotensive response to topic betaxolol in healthy Mexican volunteers.

Particular distribution of the GJB2/GJB6 gene mutations in Mexican population with hearing impairment.

BACKGROUND: Hereditary sensorineural hearing loss (SNHL) is a genetically heterogeneous disorder worldwide. Mutations in the GJB2 gene are a frequent cause of hereditary SNHL. There is a prevalence of certain mutations in various populations which suggests that specific mutations may be influenced by ethnic background. OBJECTIVE: To analyze the prevalence of GJB2, GJB6 mutations in several geographic areas of Mexico in patients with hereditary SNHL. MATERIALS AND METHODS: One hundred and forty Mexican unrelated propositi with prelingual SNHL were included in the study. All patients had three previous generations born in Mexico and belonged to no specific ethnic group. Analyses of the GJB2 and GJB6 genes and mt.1555AG mutation was not detected. CONCLUSION: We found a great variety of mutations depending on the analyzed region in patients with SNHL; 57.86% of patients had affection in one or two alleles in GJB2 or GJB6 genes whereas 42.14% were wild-type. In some cases, allele distribution depended on region. Molecular studies of more genes involved in hereditary non-syndromic SNHL are required to completely confirm the molecular basis of hearing loss in Mexican population.