Table 1.
NDD and psychiatric phenotypes in individuals heterozygous for variants disrupting DMXL2
| Case # | Sourcea | Variant type | Variant details | Individual | Sex | Age group | Inheritance | Reported NDD phenotype(s) | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ASD | DD/ID | ADHD | SCZ/psychosis | Other | ||||||||
| 1 | This report | Multigene loss | chr15:51,670,601–51,933,000 × 1 262,400 bp (DMXL2, GLDN) |
Proband (II-1) | F | Adult | Pat | + | − | + | − | +b |
| 2 | Daughter (III-1) | F | Child | Mat | + | +/− | − | − | +b | |||
| 3 | Father (I-1) | M | Adult | N.D. | − | − | − | − | +b | |||
| 4 | DECIPHER | Multigene loss | chr15:51,568,830–51,843,305 × 1 274,476 bp (DMXL2, GLDN, CYP19A1) |
Proband | M | Adult | N.D. | + | + | + | − | − |
| 5 | Canadian laboratory | Intragenic loss | chr15:51,806,694–51,843,305 × 1 36,612 bp (DMXL2) |
Proband | M | Child | N.D. | − | + | − | − | − |
| 6 | Lineagen laboratory | Intragenic gain | chr15:51,717,028–51,792,612 × 3 75,585 bp (DMXL2) |
Proband | M | Child | N.D. | + | − | + | − | +c |
| 7 | Intragenic gain | chr15:51,708,028–51,874,928 × 3 166,901 bp (DMXL2) |
Proband | M | Child | Pat | − | + | − | − | +d | |
| 8 | Multigene loss | chr15:51,735,136–52,620,104 × 1 884,969 bp (DMXL2 and 12 other genes) |
Proband | F | Adult | N.D. | − | + | + | − | +e | |
| 9 | Twin sister | F | Adult | N.D. | − | − | − | + | − | |||
| 10 | Multigene gainf | chr15:50,848,381–51,741,314 × 3 892,934 bp (DMXL2, GLDN, and 7 other genes) |
Proband | M | Child | N.D. | − | − | − | − | − | |
| 11 | Siblingg | F | Child | N.D. | − | − | − | − | − | |||
| 12 | PGC CNV data | Multigene gainf | chr15:50,888,568–51,748,611 × 3 860,044 bp (DMXL2, GLDN, and 7 other genes) |
Proband | M | Adult | N.D. | − | − | − | + | − |
| 13 | Multigene gainf | chr15:50,892,945–51,748,611 × 3 855,667 bp (DMXL2, GLDN, and 7 other genes) |
Proband | F | Adult | N.D. | − | − | − | + | − | |
| 14 | Autism Speaks MSSNG WGS data | LoF SNV | c.9081dupT [p.N3028_I3029delinsX] | Proband | M | Child | N.D. | + | − | − | − | − |
| 15 | LoF SNV | c.4387dupC [p.Q1463fs] | Probandh | F | Child | Pat | + | − | − | − | − | |
| 16 | LoF SNV | c.2239C>T [p.R747X] | Proband | M | Child | Mat | + | − | − | − | − | |
| 17 | LoF SNV | c.1618-2A>G | Proband | M | Child | Pat | + | − | − | − | − | |
Reported physical phenotypes not described elsewhere include: case #5 with mildly coarse features, dental caries, pyloric stenosis, bleeding disorder, and undergrowth; case #8 with coarctation of the aorta; case #10 with short stature and growth hormone deficiency; and case #11 with short stature and short fifth metacarpal. See the “Methods” section for details. There is no mention of psychiatric phenotyping of individuals heterozygous for an in-frame deletion in DMXL2 in the family published by Tata and colleagues [42]
ADHD, attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder; CMA, chromosomal microarray; CNV, copy number variation; DD, developmental delay; F, female; ID, intellectual disability; LoF, loss of function; M, male; Mat, maternal; N.D., not determined; Pat, paternal; PGC, Psychiatric Genomics Consortium; SCZ, schizophrenia; SNV, single nucleotide variant; WGS, whole-genome sequencing
aSee the “Methods” section for details
bSee the “Results” section for details
cEncephalopathy, speech delay, aggression/behavior issues, and vocal tics
dUnilateral ptosis, hypotonia, toe walking, and some sensory and behavioral issues
eBipolar affective disorder, anxiety, and one episode of catatonia
fBreakpoint lies within genomic extent of DMXL2
gAlso with inv(5)(q13.3q33.1)
hAlso with 15q11.2-q13.3 gain