Table 2.
Genetic and clinical data in the cohort of patients analyzed. Clinical (A) and genetic (B) features of the 15 CMT patients (16 variants) identified by NGS.
| FAMID | GENE | HGVSc | HGVSp | dpSNP ID | GENOTYPE | PHENOTYPE MIM | ACMG | Clin Var | ACMG | AY | AO | Family history | CMT subtype | CV | CV subtype | Reference |
| 882 | MFN2 | NM_001127660.1: c.[2258dupT] | NP_001121132.1: p.(Gln754AlafsTer9) | rs773371488: dupT | Heterozygous | 609260 | 5 | SCV001424047 | PVS1-PM1-PM2-PP3 | 45 | 7 | NO | 2 | >45 | Normal | Our study |
| 896 | MPZ | NM_000530.8: c.[306delA] | NP_000521: p.(Asp104ThrfsTer14) | rs281865125 delA | Heterozygous | 607791 | 5 | SCV000928852 | PVS1-PM1-PM2 | 45 | 20 | NO | 1 + 2 | >15 | Very slow | Warner et al., 1996 |
| 1196 | GDAP1 | NM_018972.2: c.[140delA] | NP_061845.2: p.(Lys47ArgfsTer3) | Heterozygous | 607831 | 5 | SCV001424519 | PVS1-PM1-PM2 | 69 | 57 | YES | 2 | >45 | Normal | Our study | |
| 1251 | SH3TC2 | NM_024577.3: c.[805 + 2T > C] | rs139052887 T > C | Homozygous | 601596 | 5 | SCV001249582.3, SCV001388540.1 | PVS1-PM2-PP3 | 45 | 20 | YES | 1 | 18 | Slow | Piscosquito et al., 2016 | |
| 564 | PMP22 | NM_153321: g.dup(17)p12 | Heterozygous | 118220 | 5 | SCV001424528 | PS3-PM1-PM2-PP3-PP4 | 44 | 41 | NO | 1 | <35 | Slow | Rautenstrauss et al., 1998 | ||
| 402 | HSPB1 | NM_001540.3: c.[570G > C] | NP_001531.1: p.(Gln190His) | Heterozygous | 606595 | 4 | SCV001424520 | PM1-PM2-PP2-PP3 | 80 | 56 | NO | 2 | 38 | Intermediate | Capponi et al., 2016 | |
| 1141 | KIF5A | NM_004984.2: c.[2868_2870delTCT] | NP_004975.2: p.(Leu957del) | rs575223790 del TCT | Heterozygous | 604187 | 4 | SCV001424521 | PM1-PM2-PM4-PP3 | 60 | 40 | YES | 5 | 40 | Intermediate | Our study |
| 580 | MTMR2 | NM_016156.5: c.[463T > C] | NP_057240.3: p.(Cys155Arg) | Heterozygous | 601382 | 4 | SCV001424522 | PM2-PM3-PP1-PP3-PP4 | 30 | 22 | YES | 2 | <35 | Intermediate | Our study | |
| 184 | KIF1A | NM_001244008.2: c.[5332C > T] | NP_001230937: p.(Arg1778Trp) | rs765668490: C > T | Heterozygous | 614213 | 4 | SCV000952011.2 | PM2-PP2-PP3-PP4 | 67 | 45 | NO | 5 | 25 | Slow | Our study |
| 721 | AGRN | NM_198576.4: c.[5851C > T] | NP_940978.2: p.(Arg1951Cys) | rs746117937: C > T | Heterozygous | 615120 | 3 | SCV001377285.1 | PM2-PP3-BP1 | 59 | 55 | NO | 2 | >15 | Very slow | Our study |
| 721 | SCP2 | NM_002979.5: c.[886C > T] | NP_001317516.1: p.(Pro296Ser) | Heterozygous | 613724 | 3 | SCV001424523 | PM2-PP3 | 59 | 55 | NO | 2 | Our study | |||
| 856 | DNM2 | NM_001005360.2: c.[890G > A] | NP_001005360.1: p.(Arg297His) | rs763894364 G > A | Heterozygous | 6482 | 3 | SCV000762731.1 | PM2-PP2-PP3 | 67 | NA | NO | 1 + 2 | <35 | Slow | Our study |
| 608 | MED25 | NM_030973.3: c.[949G > T] | NP_112235.2: p.(Gly317Cys) | rs1280659782 G > T | Heterozygous | 605589 | 3 | SCV001424524 | PM2-PP3-BP1 | 53 | 50 | NO | 2 | <35 | Intermediate | Our study |
| 962 | DYNC1H1 | NM_001376.4: c.[9919G > T] | NP_001367.2: p.(Val3307Leu) | Heterozygous | 614228 | 3 | SCV001424525 | PM1-PM2-BP4 | 36 | 34 | NO | 1 | 20 | Slow | Our study | |
| 731 | DYNC1H1 | NM_001376.4: c.[6743A > G] | NP_001367.2: p.(Glu2248Gly) | Heterozygous | 614228 | 3 | SCV001424526 | PM2-PP3 | 63 | NA | 1 | <35 | Slow | Our study | ||
| 1261 | BSCL2 | NM_001122955.3: c.[124C > T] | NP_001116427.1: p.(Arg42Cys) | rs201493373 C > T | Heterozygous | 600794 | 3 | SCV001148309.4 | PP2-BS1 | 48 | 42 | NO | 1 | >15 | Very slow | Our study |
FAM ID, Family identification; HGVSc, Nomenclature human genome variation society coding DNA; HGVSp, Nomenclature human genome variation society protein; dbSNP ID, Single nucleotide polymorphism database; ACMG, American college of medical genetics guideline; AY, Years at evaluation; AO, Age at onset; CMT subtype, Demyelinating CMT=1, Axonal CMT =2, dHMN=3, HSN=4, and Possible CMT=5; CV, Conduction velocity m/s; CV subtype, CMT subtype classification for conduction velocity; PVS1, Null variant (nonsense, frameshift, canonical ±1 or 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease (pathogenic and very strong); PM1, Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation (pathogenic and moderate); PM2, Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (pathogenic and moderate); PM3, For recessive disorders, detected in trans with a pathogenic variant (pathogenic and moderate); PM4, Protein length changes as a result of in-frame deletions/insertions in a non-repeat region or stop-loss variants (pathogenic and moderate); PP1, Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (pathogenic and supporting); PP2, Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease Pathogenic and supporting); PP3, Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.; pathogenic and supporting); PP4, Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology (pathogenic and supporting); BP1, Missense variant in a gene for which primarily truncating variants are known to cause disease (benign and supporting); BP4, Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.; benign and supporting).