موظفي النجاح

نوع المنشور

بحث أصيل

المؤلفون

النص الكامل

تحميل

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 investi-

gated the genetic cause of a complex neurodevelopmental phenotype in two Pales-

tinian 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 fam-

ily. 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 previ-

ously published candidate TECPR2 missense variants to clarify clinical outcomes and

variant classification using current approved guidelines, classifying a number of pub-

lished 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 addressin

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