Table 1.
Individual variant and phenotypic data for the entire cohort
| Individual | Sex | Age (years) | Zygosity | Inheritance | Mother’s NDD-related phenotype | Variant (NM_005096.3; NP_005087.1) | Speech delay | Motor delay | ID | ASD traits | Behavioral problems | Facial dys-morphism | GU anomalies | Other |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | male | 3 | hemizygous | maternal | none | c.205G>A (p.Asp69Asn) | yes | yes | N/A | N/A | no | no | urinary tract dilatation of left kidney on ultrasound | congenital heart defects |
| 21 | male | 18.2 | hemizygous | unknown | none | c.507A>T (p.Arg169Ser) | yes | no | yes | yes | yes | yes | hypospadias | – |
| 2 | male | 14 | hemizygous | maternal | Hx of LD | c.721G>A (p.Glu241Lys) | yes | yes | no | no | no | yes | no | history of growth hormone resistance and IGF1 deficiency (basis unknown), fasting and heat intolerance, excessive fatigue |
| 3 | male | 8 | hemizygous | maternal | none | c.905G>A (p.Arg302His) | yes | yes | N/A | yes | yes | yes | pielonephritis, vesicoureteral reflux | GERD |
| 4a | male | 21 | hemizygous | maternal | none | c.1183C>A (p.Arg395Ser) | yes | yes | yes | yes | yes | yes | hypospadias | – |
| 4b | male | 16 | hemizygous | maternal | none | c.1183C>A (p.Arg395Ser) | yes | no | yes | yes | yes | yes | no | – |
| 5 | male | 7 | hemizygous | maternal | none | c.1192C>T (p.Pro398Ser) | yes | yes | yes | yes | yes | no | no | weight <1%ile |
| 22 | male | 4 | hemizygous | unknown | unknown | c.1321C>T (p.Arg441Trp) | yes | no | yes | yes | no | yes | no | mild short stature |
| 6 | male | 7.42 | hemizygous | maternal | ADHD | c.1322G>A (p.Arg441Gln) | yes | yes | yes | yes | yes | yes | single renal cyst | constipation |
| 7 | male | 13 | hemizygous | maternal | none | c.1322G>A (p.Arg441Gln) | yes | yes | yes | yes | yes | yes | cryptorchidism, enuresis | short stature |
| 8 | male | 15 | hemizygous | maternal | Hx of LD | c.1322G>A (p.Arg441Gln) | yes | yes | yes | yes | yes | yes | hypospadias, ambiguous genitalia | short stature |
| 23 | male | 16 | hemizygous | de novo | N/A | c.1360T>C (p.Cys454Arg) | yes | yes | no | no | yes | yes | vesicoureteral reflux | short stature, microcephaly, myopia, retinopathy, GI dysmotility |
| 9a | male | 6 | hemizygous | maternal | none | c.2193G>C (p.Glu731Asp) | yes | no | yes | yes | yes | yes | no | – |
| 9b | male | 4 | hemizygous | maternal | none | c.2193G>C (p.Glu731Asp) | yes | no | yes | yes | yes | yes | no | – |
| 10 | male | 2.5 | hemizygous | maternal | dyslexia | c.2794A>G (p.Ile932Val) | yes | no | N/A | N/A | yes | yes | no | GERD, constipation |
| 11 | male | 19 | hemizygous | maternal | none | c.3371G>A (p.Arg1124Gln) | yes | no | yes | no | yes | yes | ectopic kidney | short stature, kyphoscoliosis |
| 12 | male | 5 | hemizygous | maternal | none | c.3409T>A (p.Tyr1137Asn) | yes | yes | yes | no | yes | yes | no | microcephaly |
| 24 | male | 8 | hemizygous | maternal | ADHD, Hx of delays | c.3518G>A (p.Ser1173Asn) | yes | yes | yes | yes | no | yes | no | – |
| 13 | male | 3.42 | hemizygous | de novo | none | c.3605T>A (p.Val1202Asp) | yes | yes | yes | no | yes | yes | cryptorchidism | microcephaly, short stature, weight <3%ile, kyphosis, long bone defects, Madelung deformity |
| 14 | male | 62 | hemizygous | unknown | none | c.3638T>C (p.Met1213Thr) | yes | yes | yes | no | no | no | enuresis | microcephaly, scoliosis, reflux |
| 15 | male | 16.25 | hemizygous | de novo | none | c.3820C>T (p.Arg1274Trp) | yes | yes | yes | yes | yes | yes | no | microcephaly, scoliosis |
| 16 | male | 0 | hemizygous | de novo | none | c.3880C>T (p.Arg1294Cys) | N/A | N/A | N/A | N/A | N/A | N/A | N/A | deceased |
| 25 | male | 8.5 | hemizygous | maternal | none | c.3970C>T (p.Arg1324Trp) | yes | no | yes | yes | yes | no | no | – |
| 17 | male | 8 | hemizygous | maternal | none | c.4029G>A (p.Met1343Ile) | yes | yes | no | yes | yes | no | no | GI dysmotility, joint laxity, pain & swelling, dysautonomic symptoms |
| Total | 23/23 | 15/23 | 17/20 | 15/21 | 18/23 | 18/23 | 11/23 | – | ||||||
| 18 | female | 1.5 | heterozygous, skewed XCI | maternal | none | c.671_674dup (p.Leu226TrpfsTer8) | yes | yes | N/A | N/A | no | yes | no | GERD |
| 19 | female | 1.42 | heterozygous | de novo | none | c.2255A>G (p.Tyr752Cys) | yes | yes | N/A | N/A | no | yes | no | – |
| 20 | female | 3 | heterozygous, skewed XCI | de novo | unknown | c.3880C>T (p.Arg1294Cys) | yes | yes | N/A | N/A | N/A | yes | pyelectasis | volvulus of midgut, pancreatic cysts |
| Total | 3/3 | 3/3 | 0/2 | 3/3 | 1/3 |
Individuals 4a and 4b are full siblings; individuals 9a and 9b are full siblings. ID, intellectual disability; ASD, autism spectrum disorder; GU, genitourinary; N/A, not assessed; GERD, gastroesophageal reflux disease; Hx, history; LD, learning disability; ADHD, attention deficit-hyperactivity disorder.