Biallelic mutations in UGDH cause congenital microcephaly

Hengel et al recently reported that bi-allelic loss-of-function mutations in UDP-Glucose 6-Dehydrogenase(UGDH)caused a severe epileptic encephalopathy syndrome-Jamuar syn-drome(OMIM #618792).1 The functional studies partially recapitulated the clinical phenotypes in the patient-derived cerebral organoid.A reduced number of proliferating neuronal progenitors in cerebral organoids was shown,which is a critical mechanism in congenital microcephaly(CM)whose patients were born with an occipitofrontal circum-ference(OCF)more than 2 standard deviations below average for age and sex.However,none of the reported patients in the article presented the phenotype as CM.