Table 2 Clinical and genetic characteristics of patients with variants of unknown significance (VOUS) in the cohort.
No | Age (Y) | Gender | Diagnosis | Clinical presentation | Gene panel | Panel name | WES | Gene name | Zygosity | Variant | Mutation |
|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 5 | F | AR Cerebellar ataxia, MR, and dysequilibrium syndrome 4 | Hypotonia, Developmental delay | Yes | CMS | Yes | ATP8A2 | Homozygous | c.2212- 1G > C | Autosomal rare mutation |
2 | 10 | M | Progeressive spasticity | Progeressive spasticity | Yes | Mental Retardation | Yes | SMARCC2/GRIN1 | Het./Het | c.143C > A p.(Ser48Tyr)/c.2438T > C p.(Met813Thr) | Rare and de novo |
3 | 2 | F | Muscular dystrophy | Hypotonia, Swallowing issues | Yes | CMD | Yes | GOLGA2 | Homozygous | c.2531-1G > A p.? | Splice site mutation associated with neuromuscular diseases |
4 | 13 | M | Centronuclear Myopathy | Proximal muscle weakness | Yes | Myopathy | Yes | NEB/COL6A2 | Homo./Het | c.194C > T p.(Pro65Leu)/c.2707G > A p.(Glu903Lys) | Missense mutations Functional implications in collagen function and associated disordersFrameshift mutati |
5 | 4 | M | MEGDEL syndrome | Spasticity and regression | Yes | NBIA | Yes | SERAC1 | Homozygous | c.91A > T p.(Arg31*) | Pathogenic mutation |
6 | 15 | M | Early-onset ataxia with oculomotor apraxia | Proximal muscle weakness | No | None | Yes | APTX | Heterozygous | c.793C > T p.(His265Tyr) | Missense mutation |
7 | 2 | F | UCMD | Proximal weakness, Hyperlaxity | Yes | CMD | No | COL12A1 | Homozygous | c.4287 + 5G > T p.? | Splice site mutation |
8 | 7 | F | Congenital myopathy | Proximal muscle weakness | Yes | Myopathy | No | NEB | Het./Het | c.194C > T p.(Pro65Leu) and c.7441A > G p.(Arg2481Gly) | Pathogenic mutations |
9 | 13 | M | Congenital myopathy | Proximal weakness, Scoliosis | Yes | Myopathy | No | RYR1 | Homozygous | c.6838G > T p.(Val2280Phe) | Pathogenic mutation |
10 | 12 | F | Congenital myopathy | Proximal muscle weakness | Yes | UCMD + Myopathy | No | RYR1/ TTN | Het./Het | c.2386G > A p.(Asp796Asn) and c.94012A > C p.(Thr31338Pro) + c.9262G > A p.(Val3088Met) and c.14543_14566del p.(Val4848_Val4855del) | Pathogenic mutation |
11 | 15 | F | Nemaline Myopathy | Proximal muscle weakness | Yes | Myopathy | No | TPM2 | Homozygous | c.(?_115-1)_(240 + 1_375-1)dup | In this study |
12 | 7 | F | HSP | Progeressive lower limb spasticity | No | None | Yes | ALS2 | Heterozygous | c.1649C > T p.(Pro550Leu) | Pathogenic mutation |
13 | 10 | M | HSP | Progeressive lower limb spasticity | Yes | HSP | No | KIDINS220 | Heterozygous | c.4179_4180del p.(Gln1393Hisfs*14) | Frameshift mutation (Premature termination) |
14 | 8 | M | HSP vs CMT | Walking difficulty, Dysmorphism | No | None | Yes | YARS | Heterozygous | c.37C > G p.(Leu13Val) |  |
15 | 5 | F | Pelizaeus-Merzbacher disease | Hypotonia, White matter abnormalities | No | None | Yes | Dup Xq21.31q25 | Not reported | seq[GRCh37] dup(X)(q21.31q25) chrX:g.96854170_123020334dup | In this study |
16 | 4 | M | Zellweger syndrome | Hypotonia, White matter abnormalities | No | None | Yes | PEX1 | Homozygous | c.2097dupT (p.Ile700Tyrfs) | Frameshift mutation (Premature termination) |
17 | 10 | M | LGMD | Proximal muscle weakness | Yes | CMD | No | POMT2 | Homozygous | c.1919G > A p.(Gly640Asp) | Missense mutation |
18 | 12 | F | Proximal myopathy | Proximal weakness, Scoliosis | Yes | LGMD | No | TTN | Heterozygous | c.75277C > T p.(Pro25093Ser) and c.90901C > T p.(Arg30301Cys) | Missense mutations |
19 | 5 | M | CMS | Fatigable proximal weakness | No | None | Yes | AGRN | Homozygous | c.1133G > T p.(Gly378Val) | Missense mutation |
