Table 2 Genetic findings in patients with Currarino syndrome
From: Novel MNX1 mutations and genotype–phenotype analysis of patients with Currarino syndrome
Case No. | Gene | Exon No. | Nucleotide change | Amino acid change | Mutation type | Inheritance | Reported | ACMG classification | Evidence of pathogenicity |
|---|---|---|---|---|---|---|---|---|---|
1 | MNX1 | 1 | c.124G > T | p.Gly42X | Nonsense | Maternal | No | Pathogenic | PVS1 PM2 PP4 |
2 | MNX1 | 1 | c.669-672delGCCT | p.Leu223Leufsa61 | Frameshift | Maternal | No | Pathogenic | PVS1 PM2 PP4 |
3 | MNX1 | 1 | c.264C > A | p.Cys88X | Nonsense | de novo | No | Pathogenic | PVS1 PS2 PM2 PP4 |
4 | MNX1 | 1 | c.401-402insCGCCGC | p.Ala135insAlaAla | Inframe insertion | NA | Yes | Uncertain significance | PM6 BP6 |
5a | MNX1 | 3 | c.1205insCACCAGCCCGCGCCCCAGT | p.X402Serfsa70 | Frameshift | Paternal | No | Pathogenic | PVS1 PM2 PP1 PP4 |
6a | MNX1 | 1 | c.70C > T | p.Gln24X | Nonsense | Paternal | No | Pathogenic | PVS1 PM2 PP1 PP4 |
7a | MNX1 | 1 | c.70C > T | p.Gln24X | Nonsense | Paternal | No | Pathogenic | PVS1 PM2 PP1 PP4 |
8a | MNX1 | Intron 1 | c.691 + 3G > T | – | Splice region mutation | Maternal | No | Likely pathogenic | PS3 PM2 PP1 PP4 |
9 | MNX1 | 3 | c.863G > T | p.Trp288Leu | Missense | Paternal | Yes | Likely pathogenic | PS1 PM2 PP3 |
10 | MNX1 | 2 | c.723C > A | p.Cys241X | Nonsense | Maternal | No | Pathogenic | PVS1 PM2 PP1 PP4 |
11 | MNX1 | Intron 1 | c.691 + 3G > T | – | Splice region mutation | de novo | No | Pathogenic | PS2 PS3 PM2 PP4 |
12 | TLE4 | 17 | c.1949C > T | p.Ser650Leu | Missense | de novo | No | Likely pathogenic | PS2 PM2 PP3 PP4 |
HOXB4 | 1 | c.48G > T | p.Lys16Asn | Missense | de novo | No | Likely pathogenic | PS2 PM2 PP3 PP4 | |
13 | ITIH2 | 13 | c.1623_1626delAGAG | p.Ile541Ilefsa12 | Frameshift | de novo | 0.00003252 in gnomAD | Likely pathogenic | PS2 PM2 PP4 |
14 | CDH2 | 3 | c.453G > T | p.Arg151Ser | Missense | de novo | No | Likely pathogenic | PS2 PM2 PP3 PP4 |