TECPR2-related hereditary sensory and autonomic neuropathy in two siblings from Palestine.
Palestinian
TECPR2
autonomic neuropathy
autophagy
encephalopathy
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
04 Mar 2024
04 Mar 2024
Historique:
revised:
05
01
2024
received:
11
10
2023
accepted:
17
02
2024
medline:
4
3
2024
pubmed:
4
3
2024
entrez:
4
3
2024
Statut:
aheadofprint
Résumé
Due to the majority of currently available genome data deriving from individuals of European ancestry, the clinical interpretation of genomic variants in individuals from diverse ethnic backgrounds remains a major diagnostic challenge. Here, we investigated the genetic cause of a complex neurodevelopmental phenotype in two Palestinian siblings. Whole exome sequencing identified a homozygous missense TECPR2 variant (Chr14(GRCh38):g.102425085G>A; NM_014844.5:c.745G>A, p.(Gly249Arg)) absent in gnomAD, segregating appropriately with the inheritance pattern in the family. Variant assessment with in silico pathogenicity prediction and protein modeling tools alongside population database frequencies led to classification as a variant of uncertain significance. As pathogenic TECPR2 variants are associated with hereditary sensory and autonomic neuropathy with intellectual disability, we reviewed previously published candidate TECPR2 missense variants to clarify clinical outcomes and variant classification using current approved guidelines, classifying a number of published variants as of uncertain significance. This work highlights genomic healthcare inequalities and the challenges in interpreting rare genetic variants in populations underrepresented in genomic databases. It also improves understanding of the clinical and genetic spectrum of TECPR2-related neuropathy and contributes to addressing genomic data disparity and inequalities of the genomic architecture in Palestinian populations.
Identifiants
pubmed: 38436550
doi: 10.1002/ajmg.a.63579
doi:
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
e63579Subventions
Organisme : MRF
ID : MRF-145-0006-DG-BAPL-C0788
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC-PC-18047
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_15054
Pays : United Kingdom
Informations de copyright
© 2024 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
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