Table 1.
Genetic summary of 6 patients with CACNA1A-associated neurodevelopmental disorders from our hospital.
| P1 | P2 | P3 | P4 | P5 | P6 | |
|---|---|---|---|---|---|---|
| Chromosome position | chr19:13414587 | chr19:13470563 | chr19:13356019 | chr19:13616854 | chr19:13370505 | Chr19:13235693 |
| Nucleic acid alteration | c.2101G > A | c.835C > T | c.4930G > A | c.185A > G | c.4264delC | c.4991G > A |
| Amino acid change | p. G701R | p. R279C | p. D1644N | p. Y62C | p. L1422Sfs*8 | p. R1664Q |
| Transcript | NM_023035 | NM_023035 | NM_001127221.1 | NM_001127221 | NM_001127221.1 | NM_001127221.2 |
| Exon/intron | Exon16 | Exon 6 | Exon 31 | Exon 1 | Exon 27 | Exon 32 |
| Structural domain | II | I | IV | I | IV | IV |
| Heterozygosity | Heterozygous | Heterozygous | Heterozygous | Heterozygous | Heterozygous | Heterozygous |
| Genetic pattern | AD | AD | AD | AD | AD | AD |
| Location | S6 domain II | Extracellular | S3 domain IV | Cytoplasmic | Extracellular | S4 domain IV |
| P1 | P2 | P3 | P4 | P5 | P6 | P1 |
| Mode of inheritance | De novo | Inherited from the father | De novo | De novo | Inherited from the mother | De novo |
| Mutation taster | Disease causing | Disease causing | Disease causing | Disease causing | Disease causing | Disease causing |
| POLYPHEN | Probably damaging (score: 1.000) | Possibly damaging (score: 0.939) | Probably damaging (score: 1.000) | Probably damaging (score: 0.999) | – | Probably damaging (score: 1.000) |
| PROVEAN PROTEIN | – | Deleterious (score: −5.780) | – | Deleterious (score: −6.542) | – | – |
| ACMG score | LP | P | LP | LP | LP | P |
| Functional effect | LOF | LOF | GOF | GOF | LOF | LOF |
| Final classification | P | P | P | P | P | P |
ACMG, American College of Medical Genetics; AD, autosomal dominant; P, pathogenic; LP, likely pathogenic; LOF, loss-of-function; GOF, gain-of-function.