Table 1. Mutations identified in XLID patients.
| Patient | Gene | Variant | Interpretation | LOVD variant ID |
|---|---|---|---|---|
| Patients with a family history suggestive of XLID | ||||
| 1 | AP1S2 | NM_003916.3: c.367C>T; p.(Gln123*) | nonsense variant; also present in mother and maternal grandmother | 36859 |
| 2 | ATRX | NM_000489.3: c.6975+5G>A; r.6850_6975del | variant segregates with ID in the family; skipping of exon 32 (125 bp) confirmed by RT-PCR studies | 36706 |
| 3 | ATRX | NM_000489.3: c.6244G>A; p.(Asp2082Asn) | PolyPhen2: probably damaging (score:1.000) SIFT: deleterious (score:0) MutationTaster: disease causing (P-value:1) Grantham distance: 23 highly conserved nucleotide (phyloP: 5.21) highly conserved amino acid segregation with ID in the family | 36708 |
| 4 | ATRX | NM_000489.3: c.7264_7265insT; p.(Gln2422Leufs*29) | frameshift mutation; segregation with ID | 36846 |
| 5 | CUL4B | NM_003588.3: c.2469C>G; p.(Ile823Met) | PolyPhen2: probably damaging (score:1.000) SIFT: deleterious (score:0.01) MutationTaster: disease causing (P-value:1) Grantham distance: 10 weakly conserved nucleotide (phyloP: 1.34) highly conserved amino acid segregation with ID in the family | 36889 |
| 6 | CUL4B | NM_003588.3: c.2060G>A; p.(Trp687*) | nonsense variant; segregation with ID in the family | 36890 |
| 7 | IQSEC2 | NM_001111125.2: c.2662dup; p.(Ile888Asnfs*16) | frameshift variant (de novo) | 36898 |
| 8 | KDM5C | NM_004187.3: c.2047del; p.(Ala683Profs*81) | frameshift variant; segregation with ID in the family | 36904 |
| 9 | KDM5C | NM_001146702.1: c.3084C>A; p.(Cys1028*) | nonsense variant; segregation with ID in the family | 36905 |
| 10 | MED12 | NM_005120.2: c.2444G>A; p.(Arg815Gln) | PolyPhen2: probably damaging (score:1.000) SIFT: deleterious (score:0) MutationTaster: disease causing (P-value: 1) Grantham distance: 43 highly conserved nucleotide (phyloP: 5.45) highly conserved amino acid segregation with ID in the family | 36920 |
| 11 | OPHN1 | NM_002547.2: c.1489C>T; p.(Arg497*) | nonsense variant; segregation with ID in the family | 36932 |
| 12 | UPF3B | NM_080632.2: c.1101G>C; p.(Lys367Asn) | PolyPhen2: probably damaging (score:1.000) SIFT: tolerated (score:0.3) MutationTaster: disease causing (P-value:0.861) Grantham distance: 94 weakly conserved nucleotide (phyloP: 0.61) moderately conserved amino acid segregation with ID in the family | 36963 |
| 13 | ZDHHC9 | NM_016032.3: c.286C>T; p.(Arg96Trp) | PolyPhen2: probably damaging (score 1.000) SIFT: deleterious (score:0) MutationTaster: disease causing (P-value:1) Grantham distance: 101 weakly conserved nucleotide (phyloP: 1.98) Highly conserved amino acid segregation with ID in the family | 36967 |
| Sporadic patients | ||||
| 14 | CUL4B | NM_003588.3: c.429_431dup; p.(Ser146dup) | in-frame insertion of one amino acid (serine); clinical features compatible with CUL4B mutation phenotype | 36891 |
| 15 | DLG3 | NM_021120.3: c.649C>T; p.(Arg217*) | nonsense variant | 36894 |
| 16 | SLC9A6 | NG_017160.1: g.135067656_135067991del (GRCh37/hg19) | deletion of 336 bp including exon 1 of SLC9A6 | 36955 |
| 17 | SMC1A | NM_006306.2: c.1937T>C; p.(Phe646Ser) | PolyPhen2: probably damaging (score:1.000) SIFT: deleterious (score:0) MutationTaster: disease causing (P-value:1) Grantham distance: 155 moderately conserved nucleotide (phyloP: 2.87) highly conserved amino acid clinical features compatible with SMC1A mutation phenotype | SMC1A_00033 |
| 18 | UBE2A | NM_003336.2: c.387dup; p.(Tyr130Valfs*9) | frameshift variant | 36958 |
| Female ID patient with skewed X-inactivation | ||||
| 19 | IQSEC2 | NM_001111125.2: c.3163C>T; p.(Arg1055*) | frameshift variant | 36899 |
| Patients in whom a specific syndrome was clinically suspected | ||||
| 20 | SLC16A2 | NM_006517.4: c.590G>A; p.(Arg197His) | PolyPhen2: probably damaging (score:1.000) SIFT: tolerated (score:0.07) MutationTaster: disease causing (P-value:1) Grantham distance: 29 moderately conserved nucleotide (phyloP: 2.47) moderately conserved amino acid identical variant already reported in an unrelated patient [HGMD: CM067032; published as NM_006517.3: c.812G>A; p.(Arg271His)] | 36936 |
| 21 | PHF6 | NM_032458.2: c.687T>A; p.(His229Gln) | PolyPhen2: probably damaging (score:1.000) SIFT: deleterious (score:0) MutationTaster: disease causing (P-value:1) Grantham distance: 24 moderately conserved nucleotide (phyloP: 2.79) highly conserved amino acid variant also present in mother and sister | 36728 |
LOVD, Leiden Open Variant database, www.lovd.nl.