Table 5.
Genetic characteristics: genes with most suspected variants to be related to ASD with epilepsy.
| No. | ACMG classification | Gene | Accession | Nucleotide | Amino acid | Diseases (OMIM) | Zygosity | Global frequency (ExAC) | Korean frequency (KRGDB) | Inheritance (OMIM) | ACMG |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 6 | Pathogenic | 8p23.2 duplication (2.2Mb) | |||||||||
| 20 | VOUS | SCN3A | NM_006922.3 | c.5873C > G | p.Thr1958Arg |
Epilepsy, familial focal Epileptic encephalopathy, early infantile |
Hetero | AD | PM2 | ||
| 24 | VOUS | MECP2 | NM_004992.3 | c.602C > T | p.Ala201Val |
{Autism susceptibility, X-linked 3} Mental retardation Rett syndrome Encephalopathy, neonatal severe |
Hemi | 0.0015 | 0.00643087 | PP3, PP5 | |
| 34 | VOUS | GRIN2A | NM_000833.4 | c.3059C > G | p.Ser1020Cys | Epilepsy, focal, with speech disorder and with or without mental retardation | Hetero | PM2 | |||
| 38 | VOUS | SCN1A | NM_006920.4 | c.2556+9_2556+10insG |
Dravet syndrome Epilepsy, generalized, with febrile seizures plus, type 2 Febrile seizures, familial, 3A Migraine, familial hemiplegic |
Hetero | AD | PM2 | |||
| 60 | Likely pathogenic | Xp22.2p22.33 deletion | Hetero | ||||||||
| Likely pathogenic | NLGN4X | NM_020742.3 | Whole gene deletion |
Asperger syndrome susceptibility Autism susceptibility Mental retardation |
Hetero | ||||||
| 84 | VOUS | ROBO1 | NM_002941.3 | c.3229C > T | p.Gln1077Ter | Hetero | PVS1, PM2 | ||||
| 94 | Likely pathogenic | TSC2 | NM_000548.3 | c.4744_4746del | p.Ile1582del |
Tuberous sclerosis-2 Lymphangioleiomyomatosis, somatic |
Hetero | AD | PM2, PM4, PM6 | ||
| 95 | Likely pathogenic | TSC2 | NM_000548.3 | C.2838-122G > A |
Tuberous sclerosis-2 Lymphangioleiomyomatosis, somatic |
Hetero | AD | PM2, PM6, PP5, PP4 | |||
| 121 | Likely pathogenic | MECP2 | NM_004992.3 | c.455C > G | p.Pro152Arg |
{Autism susceptibility, X-linked 3} Mental retardation Rett syndrome Encephalopathy, neonatal severe |
Hetero | XR, XD | PM2, PM5, PP3, PP5 | ||
| 122 | VOUS | ZEB2 | NM_014795.3 | c.2494G > A | p.Ala832Thr | Mowat–Wilson syndrome | Hetero | PM2 | |||
| 142 | Likely pathogenic | SYNGAP1 | NM_006772.2 | c.980T > C | p.Leu327Pro | Mental retardation | Hetero | PM2, PP5 | |||
| 143 | VOUS | LRP2 | NM_004525.2 | c.5314G > A | p.Val1772Ile | Donnai–Barrow syndrome | Hetero | PM2, PP3 | |||
| 144 | VOUS | TUBGCP6 | NM_020461.3 | c.4009G > A | p.Gly1337Arg | Microcephaly and chorioretionpathy | Hetero | 0.00001048 | PM2 | ||
Most suspected genetic variant of each ASD patients with comorbid epilepsy. OMIM, Online Mendelian Inheritance in Man; ExAC, population frequency from The Exome Aggregation Consortium; KRGDB, population frequency from the Korean Reference Genome Database; AD, Autosomal dominant; AR, Autosomal recessive; XD, X-linked dominant; XR, X-linked recessive; ACMG, The American College of Medical Genetics and Genomics guideline (Richards et al., 2015); PVS, Very strong evidence of pathogenicity; PM, Moderate evidence of pathogenicity; PP, Supporting evidence of pathogenicity. aInheritance of the gene described in OMIM. BOLD: Clinical syndromes and diseases related to neurodevelopmental disorders (ASD, ID, epilepsy).