Enhancing genetic medicine: Rapid and cost- effective molecular diagnosis for a GJB2 founder mutation for hearing impairment in Ghana

Samuel M. Adadey; Edmond Tingang Wonkam; Elvis Twumasi Aboagye; Darius Quansah; Adwoa Asante-poku; Osbourne Quaye; Geoffrey K. Amedofu; Gordon A. Awandare; Ambroise Wonkam

doi:10.3390/genes11020132

Enhancing genetic medicine: Rapid and cost- effective molecular diagnosis for a GJB2 founder mutation for hearing impairment in Ghana

Samuel M. Adadey, Edmond Tingang Wonkam, Elvis Twumasi Aboagye, Darius Quansah, Adwoa Asante-poku, Osbourne Quaye, Geoffrey K. Amedofu, Gordon A. Awandare, Ambroise Wonkam

Research output: Contribution to journal › Article › peer-review

Abstract

In Ghana, gap-junction protein β 2 (GJB2) variants account for about 25.9% of familial hearing impairment (HI) cases. The GJB2-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 GJB2-p.Arg143Trp variant. All hearing-impaired participants from 7/8 families were homozygous positive for the GJB2-p.Arg143Trp mutation using the NciI-RFLP test, which was confirmed with Sanger sequencing. The investigation of 111 individuals with isolated nonsyndromic HI that were previously Sanger sequenced found that the sensitivity of the GJB2- p.Arg143Trp NciI-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 GJB2-p.Arg143Trp NciI-RFLP-based diagnostic test had a high sensitivity for genotyping the most common GJB2 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.

Original language	English (US)
Article number	132
Journal	Genes
Volume	11
Issue number	2
DOIs	https://doi.org/10.3390/genes11020132
State	Published - Feb 2020
Externally published	Yes

Keywords

GJB2-p.R143W
Ghana
Hearing impairment
NciI-RFLP
Rapid diagnostic test

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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10.3390/genes11020132

Cite this

@article{cc349e11b3164774b4019c2e4f8e9f68,

title = "Enhancing genetic medicine: Rapid and cost- effective molecular diagnosis for a GJB2 founder mutation for hearing impairment in Ghana",

abstract = "In Ghana, gap-junction protein β 2 (GJB2) variants account for about 25.9% of familial hearing impairment (HI) cases. The GJB2-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 GJB2-p.Arg143Trp variant. All hearing-impaired participants from 7/8 families were homozygous positive for the GJB2-p.Arg143Trp mutation using the NciI-RFLP test, which was confirmed with Sanger sequencing. The investigation of 111 individuals with isolated nonsyndromic HI that were previously Sanger sequenced found that the sensitivity of the GJB2- p.Arg143Trp NciI-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 GJB2-p.Arg143Trp NciI-RFLP-based diagnostic test had a high sensitivity for genotyping the most common GJB2 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.",

keywords = "GJB2-p.R143W, Ghana, Hearing impairment, NciI-RFLP, Rapid diagnostic test",

author = "Adadey, {Samuel M.} and Wonkam, {Edmond Tingang} and Aboagye, {Elvis Twumasi} and Darius Quansah and Adwoa Asante-poku and Osbourne Quaye and Amedofu, {Geoffrey K.} and Awandare, {Gordon A.} and Ambroise Wonkam",

note = "Funding Information: Funding: This work was supported by funds from the World Bank African Centres of Excellence grant (ACE02‐ WACCBIP: Awandare) and a Developing Excellence in Leadership, Training and Science Initiative (DELTAS) Africa grant (DEL‐15‐007: Awandare). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS){\textquoteright}s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa{\textquoteright}s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (107755/Z/15/Z: to G.A.A. and A.W.) and the U.K. government; the National Institutes of Health (NIH), USA, grant number U01‐HG‐009716 to AW; and the African Academy of Science/Wellcome Trust, grant number H3A/18/001 to A.W. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: Acknowledgments: Samuel Mawuli Adadey is supported by WACCBIP DELTAS PhD fellowship and Africa Regional International Staff/Student Exchange (ARISE) II mobility fund, and Darius Quansah is supported by the WACCBIP Africa Centre of Excellence (ACE) Masters fellowship. We are grateful to all the parents, patients, control participants, and the staff of the schools for the deaf for their support during the recruitment process. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2020",

month = feb,

doi = "10.3390/genes11020132",

language = "English (US)",

volume = "11",

journal = "Genes",

issn = "2073-4425",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

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T1 - Enhancing genetic medicine

T2 - Rapid and cost- effective molecular diagnosis for a GJB2 founder mutation for hearing impairment in Ghana

AU - Adadey, Samuel M.

AU - Wonkam, Edmond Tingang

AU - Aboagye, Elvis Twumasi

AU - Quansah, Darius

AU - Asante-poku, Adwoa

AU - Quaye, Osbourne

AU - Amedofu, Geoffrey K.

AU - Awandare, Gordon A.

AU - Wonkam, Ambroise

N1 - Funding Information: Funding: This work was supported by funds from the World Bank African Centres of Excellence grant (ACE02‐ WACCBIP: Awandare) and a Developing Excellence in Leadership, Training and Science Initiative (DELTAS) Africa grant (DEL‐15‐007: Awandare). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (107755/Z/15/Z: to G.A.A. and A.W.) and the U.K. government; the National Institutes of Health (NIH), USA, grant number U01‐HG‐009716 to AW; and the African Academy of Science/Wellcome Trust, grant number H3A/18/001 to A.W. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: Acknowledgments: Samuel Mawuli Adadey is supported by WACCBIP DELTAS PhD fellowship and Africa Regional International Staff/Student Exchange (ARISE) II mobility fund, and Darius Quansah is supported by the WACCBIP Africa Centre of Excellence (ACE) Masters fellowship. We are grateful to all the parents, patients, control participants, and the staff of the schools for the deaf for their support during the recruitment process. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2020/2

Y1 - 2020/2

N2 - In Ghana, gap-junction protein β 2 (GJB2) variants account for about 25.9% of familial hearing impairment (HI) cases. The GJB2-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 GJB2-p.Arg143Trp variant. All hearing-impaired participants from 7/8 families were homozygous positive for the GJB2-p.Arg143Trp mutation using the NciI-RFLP test, which was confirmed with Sanger sequencing. The investigation of 111 individuals with isolated nonsyndromic HI that were previously Sanger sequenced found that the sensitivity of the GJB2- p.Arg143Trp NciI-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 GJB2-p.Arg143Trp NciI-RFLP-based diagnostic test had a high sensitivity for genotyping the most common GJB2 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.

AB - In Ghana, gap-junction protein β 2 (GJB2) variants account for about 25.9% of familial hearing impairment (HI) cases. The GJB2-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 GJB2-p.Arg143Trp variant. All hearing-impaired participants from 7/8 families were homozygous positive for the GJB2-p.Arg143Trp mutation using the NciI-RFLP test, which was confirmed with Sanger sequencing. The investigation of 111 individuals with isolated nonsyndromic HI that were previously Sanger sequenced found that the sensitivity of the GJB2- p.Arg143Trp NciI-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 GJB2-p.Arg143Trp NciI-RFLP-based diagnostic test had a high sensitivity for genotyping the most common GJB2 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.

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KW - Ghana

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KW - NciI-RFLP

KW - Rapid diagnostic test

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JO - Genes

JF - Genes

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Enhancing genetic medicine: Rapid and cost- effective molecular diagnosis for a GJB2 founder mutation for hearing impairment in Ghana

Abstract

Keywords

ASJC Scopus subject areas

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