Table 1.
Summary of Clinical Features of Individuals with Causative De Novo Variants in MAPK8IP3.
| Individual | De Novo Variant | p. | Sex | Age | DD and ID (IQ) | ASD | Sz | Neurological Exam | Microcephaly | Brain Anomalies | Other |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | c.65delG | p.(Gly22Alafs∗3) | M | 14 yr | moderate (48) | + | – | MH, ataxia | – | cerebellar atrophy, white-matter hyperintensity in posterior limbs of internal capsules | scoliosis |
| 2 | c.79G>T | p.(Glu27∗) | M | 4 yr | severe | – | – | MH, ataxia | – | no | – |
| 3 | c.111C>G | p.(Tyr37∗) | M | 4 yr | moderate | – | – | MH | – | no | – |
| 4 | c.1198G>A | p.(Gly400Arg) | M | 7 yr | mild | + | – | – | – | NA | – |
| 5 | c.1331T>C | p.(Leu444Pro) | M | 10 yr | moderate (49) | – | 1× gSz | MH | – | perisylvian polymicrogyria | scoliosis |
| 6 | F | 9 yr | mild | – | – | MH | – | perisylvian polymicrogyria | – | ||
| 7 | c.1574G>A | p.(Arg525Gln) | F | 3 yr | mild | – | – | – | −2.7 SD. | no | – |
| 8 | c.1732C>T | p.(Arg578Cys) | F | 5 yr | severe | – | 1× gSz | MH, SP | −2.5 SD. | cerebral atrophy, white-matter volume loss, thin CC with hypoplasia of rostrum and splenium, cerebellar atrophy | short stature |
| 9 | F | 6 yr | moderate | – | 1× gSz | MH, SP | −2.5 SD. | cerebral atrophy, white-matter volume loss, thin CC, cerebellar hypoplasia predominant in inferior vermis | short stature | ||
| 10 | c.2982C>G | p.(His994Gln) | M | 4 yr | moderate | – | gSz | MH | – | no | – |
| 11 | c.3436C>T | p.(Arg1146Cys) | F | 11 yr | mild | – | – | SP | – | mild cerebral atrophy, white-matter volume loss, thin CC | cortical visual impairment |
| 12 | F | 4 yr | severe | – | – | SP | – | short CC | – | ||
| 13 | F | 19 yr | moderate (49) | – | – | MH, unstable gait | – | white-matter volume loss, thin CC | cortical visual impairment, scoliosis |
Variant nomenclature corresponds to GenBank: NM_015133.4. Abbreviations are as follows: ASD = autism spectrum disorder; CC =corpus callosum; DD = developmental delay; ID = intellectual disability; F = female; M = male; MH = muscular hypotonia; NA = not available; SP = spasticity; and gSz = generalized seizures. Further clinical details are provided in Table S1.