César Paz-y-Miño1, Doyle Beaty2, Andrés López-Cortés2, Indira Proaño3. 1. Instituto de Investigaciones Biomédicas, Facultad de Medicina, Universidad de las Américas, Quito, Ecuador. Electronic address: cpazymino@udla.edu.ec. 2. Instituto de Investigaciones Biomédicas, Facultad de Medicina, Universidad de las Américas, Quito, Ecuador. 3. Dirección Nacional de Articulación de la Red Pública y Complementaria de la Salud Enfermedades Raras, Ministerio de Salud Pública, Quito, Ecuador.
Abstract
OBJECTIVE: The frequency of GJB2 mutations and of the del(GJB6-D13S1830) mutation has not been established among the Ecuadorian mestizo population diagnosed with autosomal recessive non-syndromic hearing loss. A genetic analysis was therefore designed in order to do so. METHODS: The sample population included 111 subjects of which 26 were autosomal recessive non-syndromic hearing loss probands. Posterior to PCR amplification, sequencing analysis of exon 2 was used for mutational detection of the GJB2 gene; a multiplex PCR method was used for detection of the del(GJB6-D13S1830) mutation. The ratio of subjects with a certain state of the mutation (heterozygous/homozygous) is expressed as a percentage and significant differences between probands and controls were calculated using Fisher's exact test; P<0.05 was considered significant. RESULTS: A total of 104 mutations belonging to 8 allelic variations were identified. The most common being the V27I (58.9%); however, as this variation is a non-pathogenic polymorphism, Q7X, with a total of 19 mutated alleles, was the most frequent mutation (18.3%). The V27I polymorphism was the only variation distributed homogenously among probands and controls (P=0.351). Based on physical analyses of multiple patients we confirm that Q7X causes a non-syndromic form of hearing loss and propose that it is a possible predominant mutation in the Ecuadorian population. CONCLUSIONS: This is the first study of its kind among the Ecuadorian population and a preliminary step in establishing GJB2 and del(GJB6-D13S1830) mutational frequencies in this population; it is also the first to report of such a high frequency of the Q7X mutation. The data presented here brings Ecuador a step closer to providing more efficient treatment for a broader number of patients; additionally, it contributes to a better understanding of the relationship between autosomal recessive non-syndromic hearing loss and mutations on the GJB2 gene.
OBJECTIVE: The frequency of GJB2 mutations and of the del(GJB6-D13S1830) mutation has not been established among the Ecuadorian mestizo population diagnosed with autosomal recessive non-syndromic hearing loss. A genetic analysis was therefore designed in order to do so. METHODS: The sample population included 111 subjects of which 26 were autosomal recessive non-syndromic hearing loss probands. Posterior to PCR amplification, sequencing analysis of exon 2 was used for mutational detection of the GJB2 gene; a multiplex PCR method was used for detection of the del(GJB6-D13S1830) mutation. The ratio of subjects with a certain state of the mutation (heterozygous/homozygous) is expressed as a percentage and significant differences between probands and controls were calculated using Fisher's exact test; P<0.05 was considered significant. RESULTS: A total of 104 mutations belonging to 8 allelic variations were identified. The most common being the V27I (58.9%); however, as this variation is a non-pathogenic polymorphism, Q7X, with a total of 19 mutated alleles, was the most frequent mutation (18.3%). The V27I polymorphism was the only variation distributed homogenously among probands and controls (P=0.351). Based on physical analyses of multiple patients we confirm that Q7X causes a non-syndromic form of hearing loss and propose that it is a possible predominant mutation in the Ecuadorian population. CONCLUSIONS: This is the first study of its kind among the Ecuadorian population and a preliminary step in establishing GJB2 and del(GJB6-D13S1830) mutational frequencies in this population; it is also the first to report of such a high frequency of the Q7X mutation. The data presented here brings Ecuador a step closer to providing more efficient treatment for a broader number of patients; additionally, it contributes to a better understanding of the relationship between autosomal recessive non-syndromic hearing loss and mutations on the GJB2 gene.
Authors: C Carranza; I Menendez; M Herrera; P Castellanos; C Amado; F Maldonado; L Rosales; N Escobar; M Guerra; D Alvarez; J Foster; S Guo; S H Blanton; G Bademci; M Tekin Journal: Clin Genet Date: 2015-10-06 Impact factor: 4.438
Authors: Nikolay A Barashkov; Vera G Pshennikova; Olga L Posukh; Fedor M Teryutin; Aisen V Solovyev; Leonid A Klarov; Georgii P Romanov; Nyurgun N Gotovtsev; Andrey A Kozhevnikov; Elena V Kirillina; Oksana G Sidorova; Lena M Vasilyevа; Elvira E Fedotova; Igor V Morozov; Alexander A Bondar; Natalya A Solovyevа; Sardana K Kononova; Adyum M Rafailov; Nikolay N Sazonov; Anatoliy N Alekseev; Mikhail I Tomsky; Lilya U Dzhemileva; Elza K Khusnutdinova; Sardana A Fedorova Journal: PLoS One Date: 2016-05-25 Impact factor: 3.240
Authors: Samuel Mawuli Adadey; Edmond Wonkam-Tingang; Elvis Twumasi Aboagye; Daniel Wonder Nayo-Gyan; Maame Boatemaa Ansong; Osbourne Quaye; Gordon A Awandare; Ambroise Wonkam Journal: Life (Basel) Date: 2020-10-28