Browsing by Author "Aboagye, E.T."

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Childhood Hearing Impairment in Senegal
(Genes, 2023) Dia, Y.; Adadey, S.M.; Aboagye, E.T.; et al.
We recently showed that variants in GJB2 explained Hearing Impairment (HI) in 34.1% (n = 15/44) of multiplex families in Senegal. The present study aimed to use community-based na tionwide recruitment to determine the etiologies and the clinical profiles of childhood HI in Senegal. Participants with early onset HI were included after clinical examination, including audiological assessment by pure tone audiometry and/or auditory brainstem response. We investigated a to tal of 406 participants from 295 families, recruited from 13/14 administrative regions of Senegal. Male/female ratio was 1.33 (232/174). Prelingual HI was the most common type of HI and accounted for 80% (n = 325 individuals). The mean age at medical diagnosis for congenital HI was computed at 3.59 ± 2.27 years. Audiological evaluation showed sensorineural HI as the most frequently ob served HI (89.16%; n = 362 individuals). Pedigree analysis suggested autosomal recessive inheritance in 61.2% (63/103) of multiplex families and sporadic cases in 27 families (26.2%; 27/103), with a consanguinity rate estimated at 93% (84/90 families). Genetic factors were likely involved in 52.7% (214/406) of the cases, followed by environmental causes (29.57%; 120/406). In 72 cases (17.73%), the etiology was unknown. Clinically, non-syndromic HI was the most common type of HI (90.6%; n = 194/214 individuals). Among families segregating syndromic cases, type 2 Waardenburg syn drome was the most common (36.3%; 4/11 families). This study revealed putative genetic factors, mostly associated with high consanguinity rate, as the leading causes of early-onset HI in Senegal. The high consanguinity could provide a good opportunity to identify variants in known and novel genes involved in childhood HI
Enhancing Genetic Medicine: Rapid and Cost-E ective Molecular Diagnosis for a GJB2 Founder Mutation for Hearing Impairment in Ghana
(genes, 2020-01-27) Adadey, S.M.; Wonkam, E.T.; Aboagye, E.T.; Quansah, D.; Asante-Poku, A.; Quaye, O.; Amedofu, G.K.; Awandare, G.A.; Wonkam, A.
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.
Global Distribution of Founder Variants Associated with Non-Syndromic Hearing Impairment
(MDPI, 2023) Aboagye, E.T.; Awandare, G.A.; et al.
The genetic etiology of non-syndromic hearing impairment (NSHI) is highly heterogeneous with over 124 distinct genes identified. The wide spectrum of implicated genes has challenged the implementation of molecular diagnosis with equal clinical validity in all settings. Differential frequencies of allelic variants in the most common NSHI causal gene, gap junction beta 2 (GJB2), has been described as stemming from the segregation of a founder variant and/or spontaneous germline variant hot spots. We aimed to systematically review the global distribution and provenance of founder variants associated with NSHI. The study protocol was registered on PROSPERO, the International Prospective Register of Systematic Reviews, with the registration number “CRD42020198573”. Data from 52 reports, involving 27,959 study participants from 24 countries, reporting 56 founder pathogenic or likely pathogenic (P/LP) variants in 14 genes (GJB2, GJB6, GSDME, TMC1, TMIE, TMPRSS3, KCNQ4, PJVK, OTOF, EYA4, MYO15A, PDZD7, CLDN14, and CDH23), were reviewed. Varied number short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs) were used for haplotype analysis to identify the shared ancestral informative markers in a linkage disequilibrium and variants’ origins, age estimates, and common ancestry computations in the reviewed reports. Asia recorded the highest number of NSHI founder variants (85.7%; 48/56), with variants in all 14 genes, followed by Europe (16.1%; 9/56). GJB2 had the highest number of ethnic-specific P/LP founder variants. This review reports on the global distribution of NSHI founder variants and relates their evolution to population migration history, bottleneck events, and demographic changes in populations linked with the early evolution of deleterious founder alleles. International migration and regional and cultural intermarriage, coupled to rapid population growth, may have contributed to re-shaping the genetic architecture and structural dynamics of populations segregating these pathogenic founder variants. We have highlighted and showed the paucity of data on hearing impairment (HI) variants in Africa, establishing unexplored opportunities in genetic traits.
Hearing loss in Africa: current genetic profle
(Springer, 2021) Adadey, S.M.; Wonkam‑Tingang, E.; Aboagye, E.T.; Quaye, O.; Awandare, G.A.; Wonkam, A.
Hearing impairment (HI) is highly heterogeneous with over 123 associated genes reported to date, mostly from studies among Europeans and Asians. Here, we performed a systematic review of literature on the genetic profle of HI in Africa. The study protocol was registered on PROSPERO, International Prospective Register of Systematic Reviews with the regis tration number “CRD42021240852”. Literature search was conducted on PubMed, Scopus, Africa-Wide Information, and Web of Science databases. A total of 89 full-text records was selected and retrieved for data extraction and analyses. We found reports from only 17/54 (31.5%) African countries. The majority (61/89; 68.5%) of articles were from North Africa, with few reports found from sub-Saharan Africa. The most common method used in these publications was targeted gene sequencing (n=66/111; 59.5%), and only 13.5% (n=15/111) used whole-exome sequencing. More than half of the studies were performed in families segregating HI (n=51/89). GJB2 was the most investigated gene, with GJB2: p.(R143W) founder variant only reported in Ghana, while GJB2: c.35delG was common in North African countries. Variants in MYO15A were the second frequently reported in both North and Central Africa, followed by ATP6V1B1 only reported from North Africa. Usher syndrome was the main syndromic HI molecularly investigated, with variants in fve genes reported: USH2A, USH1G, USH1C, MYO7A, and PCDH15. MYO7A: p.(P1780S) founder variant was reported as the common Usher syndrome variant among Black South Africans. This review provides the most comprehensive data on HI gene variants in the largely under investigated African populations. Future exomes studies particularly in multiplex families will likely provide opportunities for the discovery of the next sets of novel HI genes, and well as unreported variants in known genes to further our under standing of HI pathobiology, globally.
Psychological comorbidities in epilepsy: a cross-sectional survey among Ghanaian epilepsy patients
(Ghana Med J, 2021) Adjei, P.; Nkromah, K.; Akpalu, A.; Ohene, S.; Puplampu, P.; Aboagye, E.T.; Ganu, V.; Nartey, S.; Ae-Ngibise, K.
Objective: To evaluate the prevalence and patterns of psychiatric disorders in epilepsy patients at the Korle-Bu Teaching hospital, Accra, Ghana. Design: The study design was a cross-sectional survey Setting: The study was conducted at the Neurology Clinic of the Department of Medicine and Therapeutics, Korle Bu Teaching hospital, Accra, Ghana. Participants: A total of one hundred and sixty-six patients diagnosed with epilepsy aged at least 18 years and ac cessing services at the neurology clinic participated in the study. Main Outcome Measure: Prevalence and patterns of psychiatric disorders among patients diagnosed with epilepsy using the Brief Symptom Inventory. Results: The mean age for onset of epilepsy was 20.1 ± 16.9 years, and generalized epilepsy (73.2%) was the major type of epilepsy identified. The aetiology of the epilepsy condition was unknown in most patients (71.1%). The esti mated mean Brief Symptom Inventory scores in all the nine diagnostic psychiatry characteristics (Depression, Anxi ety, Somatization, Hostility, Phobic Anxiety, Obsessive Compulsive Disorder, Psychoticism, Interpersonal Sensitiv ity, and Paranoid Ideation) were higher in the epilepsy patients compared to the normative data scores for non-pa tients. Global Severity Index scores for females were significantly higher (p=0.002) than the scores for males on all the psychological outcomes except hostility. Conclusion: Psychological disorders were prevalent among epilepsy patients, with females more likely to experi ence psychological problems than males. The findings call for a holistic approach in managing epilepsy to highlight and manage some exceptional psychological comorbidities.
Risk Factors of Nevirapine Hypersensitivity Reactions among Hiv-1 Infected Treatment Naïve Patients at Korle-Bu Teaching Hospital (Kbth) Accra
(University of Ghana, 2015-09) Aboagye, E.T.; Dzudzor, B.; Kudzi, W.; University of Ghana, College of Basic and Applied Sciences, School of Biological Sciences, Department of Biochemistry, Cell and Molecular Biology
Dr. William Kudzi Background: The face of HIV/AIDS disease is constantly evolving, spreading among populations, and the virus mutating to become resistant to available antiretroviral drugs. Nevirapine, a NNRTI is widely used as the first-line treatment of HIV-1 infection in developing countries. Although it is generally well tolerated and effective, some individuals experience severe cutaneous and/or hepatic adverse events during the initial weeks of therapy. The risk factors associated with the development of this noxious and unintended response is inconsistent in different populations. Identification of the pre-disposing factors would aid the prescription and administration of ARV agents to the over 35 million people living with HIV. Adverse drug reactions (ADRs) are increasingly recognized as one of the most common reason for the discontinuation of treatment or switch in sub-Saharan Africa (Danq & Bhandare, 2012). Findings from this study may improve therapeutic effect at the individual level, within different population and maximize the antiviral effect in reducing the risk of serious adverse events that characterized treatment discontinuation, switch, non-adherence and hospitalization. Aim: The aim of this study was to determine the risk factors associated with the development of nevirapine-induced hypersensitivity reactions characterized by cutaneous and hepatic adverse events in HIV-1 infected treatment-naïve patients at the Korle-Bu Teaching Hospital. Methodology: Seventy three HIV-1 infected treatment-naïve Ghanaian patients were prospectively followed after nevirapine initiation at the Fevers Unit of Korle-Bu Teaching Hospital. The study involved among others, a 24 week follow-up of recruited subjects after ARV initiation, ALT and AST serum concentration determination, and physical examination for possible cutaneous nevirapine-induced rash. Blood samples were taken for DNA extractions that were used for PCR-RFLP analysis and sequencing for genotyping. Logistic regression to find association was employed to determine significant relationship. Results: Out of the 73 recruited subjects, 15.7% developed NVP-induced HSR, but the outcome had no correlation to the factors considered in this study. Conclusion: The 15.7% observed outcome is a clear manifestation of the NVPinduced HSR among HIV-1 infected Ghanaian population but none of the factors considered this study was statistically significant.