Ending a diagnostic odyssey—The first case of Takenouchi–Kosaki syndrome in an African patient

Flynn, Kaitlyn; Feben, Candice; Lamola, Lindiwe; Carstens, Nadia; Krause, Amanda; Lombard, Zané

doi:10.1002/ccr3.3966

Cited by 6 publications

(3 citation statements)

References 13 publications

(23 reference statements)

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“…This is one of very few efforts on the continent, and currently only includes patients from South Africa and the Democratic Republic of Congo, underscoring the need to accelerate broader access to genomics for global health. DDD-Africa has yielded early diagnostic advances for patients ( Flynn et al, 2021 ) and certainly lays the groundwork for future collaborations to enable the promotion and implementation of genomic medicine more broadly across the continent.…”

Section: Discussionmentioning

confidence: 99%

Identifying the genetic causes of developmental disorders and intellectual disability in Africa: a systematic literature review

Baine-Savanhu,

Macaulay,

Louw

et al. 2023

Front. Genet.

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Objective: Genetic variants cause a significant portion of developmental disorders and intellectual disabilities (DD/ID), but clinical and genetic heterogeneity makes identification challenging. Compounding the issue is a lack of ethnic diversity in studies into the genetic aetiology of DD/ID, with a dearth of data from Africa. This systematic review aimed to comprehensively describe the current knowledge from the African continent on this topic.Method: Applicable literature published up until July 2021 was retrieved from PubMed, Scopus and Web of Science databases, following PRISMA guidelines, focusing on original research reports on DD/ID where African patients were the focus of the study. The quality of the dataset was assessed using appraisal tools from the Joanna Briggs Institute, whereafter metadata was extracted for analysis.Results: A total of 3,803 publications were extracted and screened. After duplicate removal, title, abstract and full paper screening, 287 publications were deemed appropriate for inclusion. Of the papers analysed, a large disparity was seen between work emanating from North Africa compared to sub-Saharan Africa, with North Africa dominating the publications. Representation of African scientists on publications was poorly balanced, with most research being led by international researchers. There are very few systematic cohort studies, particularly using newer technologies, such as chromosomal microarray and next-generation sequencing. Most of the reports on new technology data were generated outside Africa.Conclusion: This review highlights how the molecular epidemiology of DD/ID in Africa is hampered by significant knowledge gaps. Efforts are needed to produce systematically obtained high quality data that can be used to inform appropriate strategies to implement genomic medicine for DD/ID on the African continent, and to successfully bridge healthcare inequalities.

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Section: Discussionmentioning

confidence: 99%

Identifying the genetic causes of developmental disorders and intellectual disability in Africa: a systematic literature review

Baine-Savanhu,

Macaulay,

Louw

et al. 2023

Front. Genet.

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“…A significant differentiation has been identified in SNPs of the Africans and East Asians populations (62,63). The African population has 23 unique genetic targets, of which 15 were identified with a low allele frequency and correspond to the WNT4, TYK2, CDC42, PDLIM5, FEN1 and CDΗ1 genes (56,(64)(65)(66)(67)(68), and eight were identified with a high allele frequency and correspond to the GREB1, MUC4, VEGFA, STXBP4, LILRB2, DNM3 and RNLS genes (44,69-76) (Tables I and II). The East Asian population had 11 unique genetic targets, of which ten were identified with a low allele frequency and correspond to the PACERR, CYP1B1, FAS, IL1A, ESR, VDR, CYP2C19 and MLLT10 genes (8,77-86), and one was identified with a high allele frequency and corresponds to the FN1 gene ( 8)…”

Section: Key Genetic Targets Between the Five Major Population Groups...mentioning

confidence: 99%

A global population genomic analysis shows novel insights into the genetic characteristics of endometriosis

et al. 2023

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The availability of single nucleotide polymorphisms (SNPs) associated with endometriosis, provides the opportunity for the study of this condition through SNP genomic profiles or, in other words, through disease genomic 'grammar' (DGG). The aim of the present study was to identify the genomic pedigree of endometriosis using its DGG through reported SNPs, for five major groups of the world human population, including Europeans, Africans, Americans, East Asians and South Asians. All the available allele frequencies of the endometriosis-related SNPs were analyzed based on the genome-wide association studies data from the studied population of the '1000 Genomes Project', and they were classified in the two sensitive categories of low and high allele frequencies. The final results, associated among the major groups of the human population, were annotated with beneficial knowledge from other studies. The variation of the DGG of endometriosis begins from the early beginning of the human species, as it has been associated with most genetic targets in its susceptible groups of the alleles frequency within the African population. The DGG of endometriosis has 296 and six common genetic targets of SNPs with low allele and high allele frequencies, respectively. However, there are marked differences between the five studied population groups. One disease, divergent phenotypes, with thousands of different scenarios that may cause it. The present analysis revealed notable 'key' genetic targets in the DGG of endometriosis, with the evidence of population-based heterogeneity. Further analysis of the DGG of endometriosis will allow for the understanding of the multifunctional biological pathways that exist and their diversity observed among populations, and will open new horizons in personalized medicine and functional genomics.

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“…In addition, there is an important contribution of NGS tests free-of-charge to African rare diseases patients from international research collaborations and philanthropic initiatives such as the Centers for Mendelian Genomics (CMG) [12] and the iHope foundation. All these efforts have allowed ending diagnostic odyssey in many African patients and adjusting care when possible as well as identifying new disease genes [13][14][15][16][17][18].…”

Section: Contextmentioning

confidence: 99%

Increasing African genomic data generation and sharing to resolve rare and undiagnosed diseases in Africa: a call-to-action by the H3Africa rare diseases working group

Lumaka

Carstens

Devriendt

et al. 2022

Orphanet J Rare Dis

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The rich and diverse genomics of African populations is significantly underrepresented in reference and in disease-associated databases. This renders interpreting the Next Generation Sequencing (NGS) data and reaching a diagnostic more difficult in Africa and for the African diaspora. It increases chances for false positives with variants being misclassified as pathogenic due to their novelty or rarity. We can increase African genomic data by (1) making consent for sharing aggregate frequency data an essential component of research toolkit; (2) encouraging investigators with African data to share available data through public resources such as gnomAD, AVGD, ClinVar, DECIPHER and to use MatchMaker Exchange; (3) educating African research participants on the meaning and value of sharing aggregate frequency data; and (4) increasing funding to scale-up the production of African genomic data that will be more representative of the geographical and ethno-linguistic variation on the continent. The RDWG of H3Africa is hereby calling to action because this underrepresentation accentuates the health disparities. Applying the NGS to shorten the diagnostic odyssey or to guide therapeutic options for rare diseases will fully work for Africans only when public repositories include sufficient data from African subjects.

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Ending a diagnostic odyssey—The first case of Takenouchi–Kosaki syndrome in an African patient

Abstract: First reported case of Takenouchi–Kosaki syndrome in an African patient with a de novo likely pathogenic missense variant identified in the CDC42 gene.

Cited by 6 publications

References 13 publications

Identifying the genetic causes of developmental disorders and intellectual disability in Africa: a systematic literature review

Identifying the genetic causes of developmental disorders and intellectual disability in Africa: a systematic literature review

A global population genomic analysis shows novel insights into the genetic characteristics of endometriosis

Increasing African genomic data generation and sharing to resolve rare and undiagnosed diseases in Africa: a call-to-action by the H3Africa rare diseases working group

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