Enhancing Genetic Medicine: Rapid and Cost-Effective Molecular Diagnosis for a <i>GJB2</i> Founder Mutation for Hearing Impairment in Ghana
In Ghana, gap-junction protein β 2 (<i>GJB2</i>) variants account for about 25.9% of familial hearing impairment (HI) cases. The <i>GJB2</i>-p.Arg143Trp (NM_004004.6:c.427C>T/OMIM: 121011.0009/rs80338948) variant remains the most frequent variant associated wi...
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doaj-396486d80ca5436c8a3b453762f800562020-11-25T02:05:26ZengMDPI AGGenes2073-44252020-01-0111213210.3390/genes11020132genes11020132Enhancing Genetic Medicine: Rapid and Cost-Effective Molecular Diagnosis for a <i>GJB2</i> Founder Mutation for Hearing Impairment in GhanaSamuel M. Adadey0Edmond Tingang Wonkam1Elvis Twumasi Aboagye2Darius Quansah3Adwoa Asante-Poku4Osbourne Quaye5Geoffrey K. Amedofu6Gordon A. Awandare7Ambroise Wonkam8West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra P. O. Box LG 54, GhanaDivision of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South AfricaWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra P. O. Box LG 54, GhanaWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra P. O. Box LG 54, GhanaWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra P. O. Box LG 54, GhanaWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra P. O. Box LG 54, GhanaDepartment of Eye Ear Nose & Throat, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi AK-039-5028, GhanaWest African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra P. O. Box LG 54, GhanaDivision of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South AfricaIn Ghana, gap-junction protein β 2 (<i>GJB2</i>) variants account for about 25.9% of familial hearing impairment (HI) cases. The <i>GJB2</i>-p.Arg143Trp (NM_004004.6:c.427C>T/OMIM: 121011.0009/rs80338948) variant remains the most frequent variant associated with congenital HI in Ghana, but has not yet been investigated in clinical practice. We therefore sought to design a rapid and cost-effective test to detect this variant. We sampled 20 hearing-impaired and 10 normal hearing family members from 8 families segregating autosomal recessive non syndromic HI. In addition, a total of 111 unrelated isolated individuals with HI were selected, as well as 50 normal hearing control participants. A restriction fragment length polymorphism (RFLP) test was designed, using the restriction enzyme NciI optimized and validated with Sanger sequencing, for rapid genotyping of the common <i>GJB2</i>-p.Arg143Trp variant. All hearing-impaired participants from 7/8 families were homozygous positive for the <i>GJB2</i>-p.Arg143Trp mutation using the NciI<i>-</i>RFLP test, which was confirmed with Sanger sequencing. The investigation of 111 individuals with isolated non-syndromic HI that were previously Sanger sequenced found that the sensitivity of the <i>GJB2</i>-p.Arg143Trp NciI<i>-</i>RFLP testing was 100%. All the 50 control subjects with normal hearing were found to be negative for the variant. Although the test is extremely valuable, it is not 100% specific because it cannot differentiate between other mutations at the recognition site of the restriction enzyme. The <i>GJB2-</i>p.Arg143Trp NciI<i>-</i>RFLP-based diagnostic test had a high sensitivity for genotyping the most common <i>GJB2</i> pathogenic and founder variant (p.Arg143Trp) within the Ghanaian populations. We recommend the adoption and implementation of this test for hearing impairment genetic clinical investigations to complement the newborn hearing screening program in Ghana. The present study is a practical case scenario of enhancing genetic medicine in Africa.https://www.mdpi.com/2073-4425/11/2/132hearing impairment<i>gjb2</i>-p.r143wncii-rflprapid diagnostic testghana |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Samuel M. Adadey Edmond Tingang Wonkam Elvis Twumasi Aboagye Darius Quansah Adwoa Asante-Poku Osbourne Quaye Geoffrey K. Amedofu Gordon A. Awandare Ambroise Wonkam |
spellingShingle |
Samuel M. Adadey Edmond Tingang Wonkam Elvis Twumasi Aboagye Darius Quansah Adwoa Asante-Poku Osbourne Quaye Geoffrey K. Amedofu Gordon A. Awandare Ambroise Wonkam Enhancing Genetic Medicine: Rapid and Cost-Effective Molecular Diagnosis for a <i>GJB2</i> Founder Mutation for Hearing Impairment in Ghana Genes hearing impairment <i>gjb2</i>-p.r143w ncii-rflp rapid diagnostic test ghana |
author_facet |
Samuel M. Adadey Edmond Tingang Wonkam Elvis Twumasi Aboagye Darius Quansah Adwoa Asante-Poku Osbourne Quaye Geoffrey K. Amedofu Gordon A. Awandare Ambroise Wonkam |
author_sort |
Samuel M. Adadey |
title |
Enhancing Genetic Medicine: Rapid and Cost-Effective Molecular Diagnosis for a <i>GJB2</i> Founder Mutation for Hearing Impairment in Ghana |
title_short |
Enhancing Genetic Medicine: Rapid and Cost-Effective Molecular Diagnosis for a <i>GJB2</i> Founder Mutation for Hearing Impairment in Ghana |
title_full |
Enhancing Genetic Medicine: Rapid and Cost-Effective Molecular Diagnosis for a <i>GJB2</i> Founder Mutation for Hearing Impairment in Ghana |
title_fullStr |
Enhancing Genetic Medicine: Rapid and Cost-Effective Molecular Diagnosis for a <i>GJB2</i> Founder Mutation for Hearing Impairment in Ghana |
title_full_unstemmed |
Enhancing Genetic Medicine: Rapid and Cost-Effective Molecular Diagnosis for a <i>GJB2</i> Founder Mutation for Hearing Impairment in Ghana |
title_sort |
enhancing genetic medicine: rapid and cost-effective molecular diagnosis for a <i>gjb2</i> founder mutation for hearing impairment in ghana |
publisher |
MDPI AG |
series |
Genes |
issn |
2073-4425 |
publishDate |
2020-01-01 |
description |
In Ghana, gap-junction protein β 2 (<i>GJB2</i>) variants account for about 25.9% of familial hearing impairment (HI) cases. The <i>GJB2</i>-p.Arg143Trp (NM_004004.6:c.427C>T/OMIM: 121011.0009/rs80338948) variant remains the most frequent variant associated with congenital HI in Ghana, but has not yet been investigated in clinical practice. We therefore sought to design a rapid and cost-effective test to detect this variant. We sampled 20 hearing-impaired and 10 normal hearing family members from 8 families segregating autosomal recessive non syndromic HI. In addition, a total of 111 unrelated isolated individuals with HI were selected, as well as 50 normal hearing control participants. A restriction fragment length polymorphism (RFLP) test was designed, using the restriction enzyme NciI optimized and validated with Sanger sequencing, for rapid genotyping of the common <i>GJB2</i>-p.Arg143Trp variant. All hearing-impaired participants from 7/8 families were homozygous positive for the <i>GJB2</i>-p.Arg143Trp mutation using the NciI<i>-</i>RFLP test, which was confirmed with Sanger sequencing. The investigation of 111 individuals with isolated non-syndromic HI that were previously Sanger sequenced found that the sensitivity of the <i>GJB2</i>-p.Arg143Trp NciI<i>-</i>RFLP testing was 100%. All the 50 control subjects with normal hearing were found to be negative for the variant. Although the test is extremely valuable, it is not 100% specific because it cannot differentiate between other mutations at the recognition site of the restriction enzyme. The <i>GJB2-</i>p.Arg143Trp NciI<i>-</i>RFLP-based diagnostic test had a high sensitivity for genotyping the most common <i>GJB2</i> pathogenic and founder variant (p.Arg143Trp) within the Ghanaian populations. We recommend the adoption and implementation of this test for hearing impairment genetic clinical investigations to complement the newborn hearing screening program in Ghana. The present study is a practical case scenario of enhancing genetic medicine in Africa. |
topic |
hearing impairment <i>gjb2</i>-p.r143w ncii-rflp rapid diagnostic test ghana |
url |
https://www.mdpi.com/2073-4425/11/2/132 |
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