Table 2.
Proband phenotypes and molecular data
|
Proband |
|||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | |
| Sexa | M | M | F | M | M | F | F | M | M | F | F | M | F |
| Age (years) | 2 | 9 | 8 | 13 | 11 | 4 | 3 | 11 | 18 | 13 | 22 | 18 | 13 |
| Ethnicityb | NE | NE | NE | Arab | NE | NE + A | NE | NE | NE | NE | NE | NE + H | NE |
| Molecular data | |||||||||||||
| Variant | p.Arg89 Glyfs∗8 |
p.Leu229Phe | p.? | p.Lys251 Asn |
p.Arg256Gly | p.Phe 267del |
p.Gly271 Asp |
p.Ile301 del |
p.Arg362 Cys |
p.Ser541 Tyr |
p.Arg625 Pro |
p.Arg753 Trp |
p.Pro298 Ser |
| Variant typec | FS | D1 | splice | D1 | D1 | D1Δ | D1 | D1Δ | D1 | D2 | D2 | D2 | D1 |
| ATPase functiond | N/A | − | N/A | − | + | + | + | − | − | ++ | − | − | − |
| DD and IDe | |||||||||||||
| Gross motor delay | mild | mod | mild | sev | mod | mod | sev | sev | mild | mild | mild | absent-mild | mild |
| Fine motor delay | mild | mod | + | + | + | − | + | + | + | + | + | + | + |
| Speech delay | − | mild-mod | sev | sev | mild | mod | sev | sev | mod | mod | mild | − | mod |
| ID | − | − | mod | sev | − | mild-mod | sev | sev | mild | mild | mild-mod | − (↓IQ) | mod |
| Neurological and psychiatric disorders | |||||||||||||
| ADHD | − | + | − | − | + | − | − | − | + | + | − | + | − |
| Autism | − | + | −f | − | − | − | − | + | − | − | − | + | − |
| Anxiety | − | + | − | − | + | − | − | − | − | + | − | + | − |
| Hypotonia | + | + | + | + | + | + | + | + | + | + | + | − | + |
| Epilepsy | − | − | − | −g | + | − | − | − | − | + | − | + | − |
| Tremor | + | − | − | − | − | − | − | − | − | − | + | + | + |
| Macrocephalyh | + | + | − | rel | + | + | + | + | − | + | + | + | + |
| Abnormal MRI | − | + | + | + | + | + | + | + | + | + | + | − | + |
| Congenital defects and other featuresi | |||||||||||||
| Dysmorphic | + | + | − | + | − | + | + | + | − | − | + | − | + |
| MSK | + | + | + | + | − | − | − | + | + | + | + | + | − |
| Ophthalmic | − | − | − | + | + | + | + | + | + | − | + | + | − |
| GI | + | + | + | − | + | − | − | + | − | + | + | + | − |
| GU | + | + | + | − | − | − | − | + | − | − | − | − | + |
| Cardiac | − | − | − | − | − | − | + | − | − | − | − | + | + |
Aggregated phenotypic data for the 13 probands in our cohort. Unless otherwise noted, a plus sign (+) indicates the presence of the symptom or finding, and a minus sign (−) indicates the absence of the symptom or finding.
Sex assigned at birth: M, male; F, female.
NE, northern European; A, Asian; H, Hispanic; +, proband shares both ancestries.
FS, frameshift; D1Δ, in-frame deletion in D1; D1 or D2, missense in this domain.
ATPase function was higher (+), much higher (++), or lower (−) than wild-type function (see Figure 2C). N/A, not available.
DD is qualified as mild (≤2× months to milestone), moderate (mod; >2× normal), or severe (sev; milestone never reached), and ID is based on an IQ score < 70 and/or clinical impression: mild IQ = 55–70, moderate IQ = 35–55, and severe IQ < 35 according to DSM-IV criteria. Absent-mild, absent to mild; mild-mod, mild to moderate.
Some features of autism.
EEG with epileptic activity but no clinical seizures.
Macrocephaly was absolute (+) or relative (rel).