Enhancing Genetic Medicine: Rapid and Cost-E ective Molecular Diagnosis for a GJB2 Founder Mutation for Hearing Impairment in Ghana
Date
2020-01-27
Journal Title
Journal ISSN
Volume Title
Publisher
genes
Abstract
In Ghana, gap-junction protein 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-e ective 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 non-syndromic
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 di erentiate 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.
Description
Research Article
Keywords
hearing impairment, GJB2-p.R143W, NciI-RFLP, rapid diagnostic test, Ghana