Table 1 Comparison of clinical findings in patient II:4, in the spontaneous rat mutant[7] and in knockout mice[20–22]
WWOX | MCPH | Retinopathy | Stature | Seizures | Brain abnormalities | Dev. delay | Blood count, metabolism | Death | |
|---|---|---|---|---|---|---|---|---|---|
II:4 | p.Arg54* homozygous | + | RP, optic atrophy | Short, growth retardation | + | • Supratentorial atrophy | + | • No metabolic disorder | 16 mo. |
• Centr./cortical atrophy | • Normal blood count | ||||||||
• Hypoplasia of CC | • No tumors | ||||||||
• Hippocamp. dysplasia | |||||||||
• Temporal lobe hypotrophy | |||||||||
• Hippocampal malformation | |||||||||
• Gyral pattern anomaly | |||||||||
Rat | p.Leu371Thrfs*41 homozygous (functional null, no protein produced) | n.d. | n.d. | Dwarfism | + | Extracellular vacuoles (hippocampus, amygdala) | + | • Hypogonadism1 | 3–12 weeks |
• No metabolic disorder | |||||||||
• Bone metabolic disease (mild) | |||||||||
• No tumors | |||||||||
Mouse | Homozygous knockout | n.d. | n.d. | Dwarfism | no | n.d. | + | • Hypogonadism2 | 2–3 weeks |
• Metabolic disorder3 | |||||||||
• Bone metabolic disease (severe) | |||||||||
• Osteosarcoma4 |