Table 1 Genetic findings in investigated families with HMSN
From: Expanding the genetic spectrum of hereditary motor sensory neuropathies in Pakistan
S. No. | Gene (OMIM accession #): associated disease | Variant | gnomAD(V4.0) frequency | Revel score | PhyloP score | Pathogenicity ACMG class | Novelty status |
|---|---|---|---|---|---|---|---|
Family 1 | GDAP1 (OMIM: 214400): Charcot-Marie-Tooth disease, type 4 A | c.310 + 4 A > G, p.? | 0.00000006.238 |  | 3.808 | Uncertain significance (PM2, PM3: supporting, PP3) | Novel |
Family 2 | SETX (OMIM: 606002): Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 | c.5948_5949del, p.(Asn1984Profs*30) | 0.00 | Â | 5.828 | Pathogenic (PVS1, PM2, PM3: supporting, PP1: moderate) | Novel |
Family 3 & 4 | IGHMBP2 (OMIM: 616155): Charcot-Marie-Tooth disease, axonal, type 2 S | c.1591 C > A, p.(Pro531Thr) | 0.00001736 | 0.678 | 2.743 | Pathogenic (PS3, PP3, PM2, PP2, PP1, PM3) | PMID: 25,439,726 PMID: 37,366,078 Reported in Clinvar with conflicting interpretation |
Family 5 | NARS1 (OMIM: 619091): Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive | c.1633 C > T, p.(Arg545Cys) | 0.00001363 | 0.814 | 9.491 | Likely Pathogenic (PP1, PM3, PM2, PP3, PP2, PP5) | PMID: 32,788,587 PMID: 32,738,225 Reported in Clinvar as pathogenic |