Table 1. List of 9 HACE1 mutations, including the mutation reported in this study, associated with a neurodevelopmental disorder.
| Family | Descent | No. affected | Variant type | Variant | hg19 coordinate | Clinical features |
|---|---|---|---|---|---|---|
| IA14 | Pakistani | 5 Siblings/ cousins | Homozygous | p.R219* (rs869025280) | 6:105244863 | Hypotonia, developmental delay, slowly progressive bilateral lower limb spasticity, wheelchair bound, myoclonic epilepsy, ocular abnormalities, skeletal defects, abnormal MRI findings (cerebral atrophy, ventricular dilatation) |
| IB14 | German | 3 Siblings | Homozygous and compound heterozygous | p.R748* (rs869025281) p.P674Ffs*5 (rs869025282) | 6:105198317 6:105219259 | Developmental delay, hypotonic/ataxic movement, facial muscular hypotonia with inarticulate speech, myoclonic epilepsy, bilateral lower limb spasticity, waddling gait, skeletal defects, abnormal MRI findings (hypoplastic corpus callosum, cerebral atrophy, enlarged ventricles) |
| IIA15 | 1 | Compound heterozygous | p.Q152* (rs869025284) p.Q618Vfs*3 (rs751809418) | 6:105280997 6:105224626 | Intellectual disability, combination of hypotonia, dystonia and spasticity, inability to ambulate, abnormal MRI findings (hypoplastic corpus callosum, brain atrophy) | |
| IIB15 | 1 | Homozygous | p.R269* (rs750371878) | 6:105244541 | ||
| IIC15 | 1 | Homozygous | p.C80* (rs761086584) | 6:105297103 | ||
| IID15 | 3 Siblings | Biparental homozygous | p.L832del (rs869025283) | 6:105192055 | ||
| IIIA | Indian | 1 | Homozygous | p.W370* | 6:105233159 | Intellectual disability, developmental delay, myoclonic epilepsy, hypotonia, broad-based, crouched gait, iris heterochromia, hypopigmented body hair, skeletal defect (proximal femoral focal dysplasia), abnormal MRI findings (hypoplastic corpus callosum, lesions) |
Abbreviations: HACE1, HECT domain and ankyrin repeat-containing E3 ubiquitin-protein ligase 1; MRI, magnetic resonance imaging.