A rare variant in CENPJ caused microcephaly in two unrelated families with a range of different phenotypes

Mutations in at least eight different genes having roles in either cell division or DNA repair, can cause autosomal recessive primary microcephaly (MCPH). Since it is a rare condition most mutations are identified in consanguine families from Iran, Pakistan and India. MCPH is defined by a reduction in head circumference (OFC – occipito‐frontal head circumference) as four standard deviations below the age‐ and sex‐matched population mean. However mainly intellectual disability (ID) is regarded as additional clinical findings; recent reports add seizures, epilepsy and other neurological findings to the MCPH phenotype 1, 2. Etiologically, MCPH is heterogeneous including both genetic and environmental causes as congenital infections, fetal alcohol spectrum disorders and drugs taken during pregnancy.To date eight genes (harboring 150 different mutations) have been identified for autosomal recessive MCPH and more than 250 MCPH families have been described. Here we report two unrelated families from Kohgiluyeh and Boyer-Ahmad Province with MCPH due to a mutation in CENPJ gene. The variant 13-25457439-C-T is rare and the observed phenotypes are drastically different even between affected cases from the same family.

Keywords:

autosomal recessive primary microcephaly , founder variant , CENPJ