Table 2.
List of the six truncating and five indel inframe variants identified during the screening of the 111 X-linked synaptic genes in 285 ASD and SCZ patients
| Gene | Variant | Variant type | Already described | Frequencies
|
Comments | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Disease | Sex | ASD | SCZ | CONT | Inheritance | Familial info | |||||
| MAOB | c.1342C > T p.R448X |
Nonsens | No | SCZ | M | 0/142 | 1/332 | 0/190 | Mother | 1 SCZ brother does not have the variant | Removes the TM, IM and one part of the cytoplasmic domain. |
| P2RY4 | c.1043G > A p.W348X |
Nonsens | rs41310667 | Both | M | 2/130 | 2/140 | 3/190 | n.a. | n.a. | Found in the three cohorts with similar frequencies. It might not affect protein function |
| PCDH11X | c.3034-1G > A | Splice | No | SCZ | F | 0/139 | 1/113 | 0/190 | n.a. | n.a. | Affects the end of the shortest isoform. Nonsense polymorphisms are described in dbSNP in the last exon, which is removed |
| PLXNB3 | c.1A > G p.M1? |
Unknown | No | SCZ | M M |
0/142 | 2/325 | 0/190 mother |
Mother | 1 SCZ sister has the variant 1 SCZ sister does not have the variant |
This first methionine codon is unlikely to be the real initiator codon. It is not conserved between species and does not match the Kozak consensus sequence. |
| HS6ST2 | c.23delT p.V8AfsX26 |
Indel (fshift) | No | SCZ | F | 0/142 | 1/143 | 1/190 | Mother | The SCZ half-brother has the variant | Found in a girl from the CONT cohort. The variant is inherited from her unaffected father. It might be a polymorphism. |
| IL1RAPL1 | c.1100-1106 delTACTCTT p.I367fsX6 |
Indel (fshift) | No | ASD | F | 1/422 | 0/143 | 0/189 | de novo | No familial history | Affects protein function (Piton et al.).51 |
| CACNA1F | c.2440 delGAGGAAGAA p.E814-816del |
Indel (inf) | No | Both | Both | 3/142 | 9/142 | n.a. | n.a. | n.a. | Deletion/insertion of one or several Glu in a region with Glu repetition. |
| PAK3 | c.525delGAT p.D175del |
Indel (inf) | No | SCZ | M | n.a. | 1/94 | n.a. | n.a. | n.a. | Deletion of one Asp in a region with Glu repetition. It might not have a damaging effect on protein function. |
| GABRQ | c.1432delATT p. I478del |
Indel (inf) | No | Both | M | 1/141 | 1/143 | n.a. | n.a. | n.a. | One polymorphism I478F was earlier described at this position. It might not be a critical amino acid for the protein. |
| GPR50 | c.1505-1516 del12bp p. 502-505del |
Indel (inf) | No | Both | Both | 57/142 | 66/143 | n.a. | n.a. | n.a. | Already described with no association found with SCZ. |
| ATP6AP1 | c.97insGCGGCG p.A33_A34insAA |
Indel (inf) | No | Both | Both | 2/142 | 1/143 | n.a. | n.a. | n.a. | Insertion of 2 Ala found in the two cohorts. It might be a polymorphism. |
Abbreviations: ASD, autism spectrum disorder; CONT, control population; F, female; fshift, frameshift; IM, intermembrane domain; inf, in frame; M, male; n.a., non available; SCZ, schizophrenia; TM, transmembrane domain.