Table 1.
Overview of genomic variants identified in this study
| Patient ID | Gender | Age at diagnosis | Gene | Variant | Inheritance | Severity of ID or DD | Phenotype features |
|---|---|---|---|---|---|---|---|
| Known gene—known variant | |||||||
| FIN3-3 | M | 12 | PPP2R5D | NM_006245.4:c.592G > A:p.(E198K) | Suspected de novo* | Severe | Classical |
| FIN11-3 | F | 24 | CYFIP2 | NM_001291722.2:c.1993G > A:p.(E665K) | De novo | Moderate | Mild phenotype, no epilepsy |
| FIN17-3 | M | 18 | MED12 | NM_005120.3:c.2881C > T:p.(R961W) | X-linked | Mild | Classical |
| FIN24-3 | F | 14 | ACTB | NM_001101.5:c.1043C > T:p.(S348L) | De novo | Mild | Classical |
| FIN37-3 | F | 12 | DYNC1H1 | NM_001376.5:c.4700G > A:p.(R1567Q) | De novo | Severe | Classical |
| FIN52-1 | F | 53 | HUWE1 | NM_031407.7:c.9208C > T:p.(R3070C) | X-linked (suspected de novo)* | Severe | Classical, female |
| Known gene—novel variant | |||||||
| FIN6-3 | F | 10 | HNRNPK | NM_031263.4:c.1294delG:p.(D432fs) | Suspected de novo* | Moderate | Classical, high pain tolerance |
| FIN12-2 | M | 28 | ARX | NM_139058.3:c.558_560dup:p.(P187dup) | X-linked*** | Moderate | Resembles Partington's disease |
| FIN14-3 | M | 35 | CTBP1 | NM_001328.3:c.158_160del:p.(F53del) | De novo | Severe | Frontal bossing, growth retardation, cortical atrophy, no enamel defect |
| FIN20-3 | M | 20 | CHAMP1 | NM_032436.4:c.1858A > T:p.(K620*) | De novo | Moderate—severe | Frontal hypoplasia in MRI |
| FIN33-3 | M | 12 | RAI1 | NM_030665.4:c.3594G > T:p.(R1198S) | De novo | Mild | Classical |
| FIN36-3 | F | 30 | LAMB1 | NM_002291.2:c.5002delG:p.(E1668fs) + c.2315-28A > G (splicing branch point) | AR (comp het) | Moderate | Cobblestone cortical malformation, cystic lesions in cerbellum in MRI |
| FIN38-3 | F | 9 | CRADD | NM_003805.5:c.2 T > C:p.(M1?) + NM_003805.5:c.509G > A:p.(R170H)^^^ | AR (comp het) | Mild | Pachygyria in MRI |
| FIN42-3, FIN42-7 | M, M | 20, 12 | P4HTM | NM_177939.2:c.1238C > T:p.(P413L) | AR (homozygous) | Severe-profound | Increased BMI |
| FIN49-1 | M | 74 | SCN1A | NM_001202435.3:c.1891A > G:p.(M631V) | Suspected de novo** | Profound | Crunched gait |
| FIN53-1 | F | 72 | TRIO, SON | NM_007118.4:c.3908C > T:p.(T1303I) + NM_001291412.2:c.953A > C:p.(Q318P) | Suspected de novo** | Moderate | Dual molecular diagnosis |
| FIN-ID4-3 | M | 15 | KIAA2022 | NM_001008537.3:c.3244C > T:p.(Q1082*) | X-linked (de novo) | Severe | Gastroesofageal reflux |
| FIN-ID8-3 | F | 21 | GRIN2A | NM_001134408.2:c.452_463del:p.(I151_A155delinsT) | AD inherited | Moderate | Dual diagnosis: classical epilepsy, unknown syndrome |
| FIN-ID10-3 | F | 22 | ANKRD11 | NM_001256183.2:c.6793delG:p.(A2265fs) | De novo | Moderate | Dual diagnosis, Mayer-Rokitansky |
| Known gene—novel variant—phenotypic expansion | |||||||
| FIN5-3 | M | 39 | SAMD9L | NM_001350084.2:c.2722A > G:p.(I908V) | De novo | Moderate | Expansion: ataxia-pancytopenia not found |
| FIN8-3 | M | 41 | BCL11A | NM_022893.4:c.977C > A:p.(T326K) | De novo | Moderate | Expansion: fHb normal |
| FIN28-3 | F | 17 | MECP2 | NM_001110792.2:c.1174_1199del:p.(V392fs) | X-linked (suspected de novo)* | Mild | Expansion: mild phenotype |
| FIN35-3 | F | 17 | MYT1, (COL9A2)^ | NM_004535.3:c.790G > C:p.(E264Q) + NM_001852.4:c.1145G > T:p.(G382V) | De novo | Moderate | Expansion: extended phenotype, dual diagnosis |
| FIN-AIC3-3 | F | 16 | ZC3H14 | NM_207661.2:c.1177 + 9 T > C (splice region) | AR (homozygous) | Severe | Expansion: severe multisystem disease |
| Alternate inheritance model | |||||||
| FIN7-3 | M | 41 | UBA7 | NM_003335.3:c.1904 + 3A > G (splicing) | Mosaic | Moderate | Novel phenotype |
| FIN46-3 | M | 50 | DDX47 | NM_016355.4:c.1129C > A:p.(R377S) | suspected de novo^^ | Profound | Severe newborn disease |
| FIN-ID9-3 | M | 27 | DHX58 | NM_024119.3:c.1910G > A:p.(S637N) | De novo | Severe | Severe newborn disease |
| Candidate variants In potential novel genes | |||||||
| FIN4-3 | M | 26 | NTRK1 | NM_002529.3:c.2271C > G:p.(Y757*) + c.2271C > T:p.(Y757 =) (mixture of both variants) | Mosaic | Moderate-severe | Lennox epilepsy |
| FIN21-3 | M | 31 | SYPL1 | NM_006754.4:c.152G > A:p.(C51Y) | AR (homozygous) | Mild | Novel phenotype |
| FIN23-3 | M | 20 | ITPR2 | NM_002223.4:c.541A > G:p.(K181E) | De novo | Mild-moderate | Resembles Gillespie syndrome (ITPR1) |
| FIN27-3 | M | 17 | ZKSCAN1 | NM_001287054.3:c.1302C > G:p.(F434L) | De novo | Severe | Novel syndrome |
| FIN32-3 | F | 35 | ZFR | NM_016107.5:c.2667C > G:p.(D889E) | De novo | Mild | Novel phenotype |
| FIN45-3 | F | 51 | POLR2F | NM_001301130.2:c.294-2A > G (splicing) | De novo | Profound | Severe newborn disease |
| FIN47-2 | M | 55 | DNAH3 | NM_017539.2:c.11965A > G:p.(I3989V) | Suspected de novo^^ | Profound | Severe newborn disease |
| FIN-ID3-1, FIN-ID3-3 | F, M | 68, 56 | ERGIC3 | NM_015966.3:c.717 + 1G > A (splicing) | AR (homozygous) | Mild | Novel phenotype |
| FIN-AIC2-3 | F | 31 | KIF1B | NM_183416.4:c.2066C > T:p.(P689L) + NM_015074.3:c.2543C > T:p.(P848L) | AR (comp het) | Severe | Severe newborn disease |
| Structural variants | |||||||
| FIN10-3 | F | 23 | 21qdel | UPD21q22.12–22, 2.7 Mb del (DYRK1A; KCNJ6) | Mosaic | Severe | Resembles DYRK1 phenotype |
| FIN43-3 | M,M | 2 | 16p13.11del | 1.25 Mb deletion (NDE1) paternal allele | AR (heterozygous; no second allele found) | Severe | Microcephaly, simplified gyral pattern |
| FIN48-2 | M | 62 | 22q13.33del | 106 kb del (SHANK3) | Suspected de novo* | Severe | Classical |
*Suspected de novo; Heterozygous in affected proband, however DNA of one of the unaffected parent(s) unavailable to confirm this
**Suspected de novo; Heterozygous in affected proband, however DNA of both unaffected parent(s) unavailable to confirm this; Variant was excluded from unaffected sibling
***variant also present in brother with trisomie 21
^not a known ID gene but could contribute to the skeletal phenotype in this patient
^^Suspected de novo; Heterozygous in affected proband, however DNA of one of the unaffected parent(s) unavailable to confirm this. Variant was excluded from unaffected sibling
^^^R170H is a known pathogenic variant in trans with novel variant NM_003805.5:c.2 T > C:p.(M1?)