ClinVar

In 2 unrelated patients from the Druze population in Israel with microcephalic osteodysplastic primordial dwarfism type II (MOPD2; 210720), Weiss et al. (2020) identified homozygosity for a G-A transition in the -1 position of intron 17 (c.3465-1G-A, NM_006031.5) of the PCNT gene. In patient 1 the mutation was identified by whole-exome sequencing, and in patient 2 it was identified by direct sequencing of the PCNT gene. The parents of patient 1 were mutation carriers. The c.3465-1G-A mutation was reported in heterozygous state in 4 individuals from South Asia in the gnomAD database (allele frequency of 0.0001) and was not present in the Greater Middle East Variome Project database. Sequencing of lymphoblastoid cell cDNA from patient 1 and his parents revealed a 2-bp deletion at the beginning of exon 18 due to the activation of a cryptic splice site, resulting in a frameshift and premature termination (Ala1157ProfsTer36). Weiss et al. (2020) concluded that this is a founder mutation.