Summary of (candidate) syndromic and non-syndromic intellectual disability genes and their respective mutations that were identified in the investigated families
| Gene ID | Family ID | NM number | cDNA level change | Protein level change | Mutation class | Supporting evidence | Phylo-P | Go terminology |
|---|---|---|---|---|---|---|---|---|
| Pathogenic mutations | ||||||||
| DDHD2 | W10-1338 | NM_015214.2 | c.1804_1805insT; c.2057delA | p.Thr602IlefsX18; p.Glu686Glyfs*35 | + | 2nd family, E, T, D | 3.9 3.0 | Lipid catabolic process; intracellular protein transport |
| SLC6A8† | W10-2749 | NM_005929.3 | c.1005_1007delCAA | p.Asn336del | + | MIM300352 (XL-ID), E, T, D | 4.2 | Creatine metabolic process; muscle contraction |
| SLC9A6† | W08-0135 | NM_001042537.1 | c.1639G>T | p.Glu547* | + | MIM300243 (XL-ID), E, T, D | 3.1 | Amino acid transport; neurotransmitter transport |
| Mutations classified as potentially pathogenic | ||||||||
| BCORL1† | W07-1601 | NM_021946.4 | c.2459A>G | p.Asn820Ser | ± | E, P, C | 3.1 | Regulation of transcription; chromatin modification |
| MCM3AP | W05-385 | NM_003906.3 | c.2743G>A | p.Glu915Lys | ± | E, P, C | 6.0 | DNA replication; protein import into nucleus |
| PTPRT | W09-1109 | NM_133170.3 | c.4094C>T; | p.Thr1365Met; | ± | E, P, C, D | 3.5 | Protein tyrosine phosphatase activity |
| .arr snp 20q12q13.11(SNP_A-2168377->SNP_A-4194425)x1 | ||||||||
| SYNE1 | W10-1137 | NM_182961.2 | c.1964A>G; c.9262G>A; c.11675T>C | p.Gln655Arg; p.Ala3088Thr; p.Leu3892Ser | ± | MIM612998, MIM610743, E, P, C, D | 4.8 5.8 4.8 | Golgi organisation; cell death; cytoskeletal and nuclear matrix anchoring at nuclear membrane; muscle cell differentiation |
| ZNF582 | W11-3472 | NM_144690.1 | c.193T>G; c.1034G>A | p.Trp65Gly; p.Gly345Glu | ± | E, P, C, D | 1.4 3.6 | DNA dependent regulation of transcription |
Upper section: pathogenic mutations (+). Lower section: variants labelled as potentially pathogenic (±). See figure 2 for the progressive variant classification scheme.
Supporting evidence column: (E) gene is expressed in brain/neuronal tissue according to the expressed sequence tags database (http://www.ncbi.nlm.nih.gov/dbEST/); (P) effect of the mutation on protein level is predicted as disease causing/damaging by either SNPs&Go16 and/or PolyPhen-217; (C) the altered amino acid is conserved among vertebrates; (T) the mutation is predicted to result in nonsense-mediated mRNA decay and/or truncated protein; and (D) the mutation(s) reside in functional domain of the protein.
The phylo-P score is a measurement of conservation at each base in the DNA using genomic information of 44 vertebrates.41
†Gene located on chromosome X.
XL-ID, X-linked intellectual disability.