ClinVar

In a boy, born of unrelated parents of French and Maghreb origin (family 3) with neurodevelopmental disorder with hypotonia and cerebellar atrophy (NEDHCAS; 618879), Nguyen et al. (2020) identified compound heterozygous missense mutations in the PIGK gene: a c.479A-C transversion (c.479A-C, NM_005482.3) in exon 5, resulting in tyr160-to-ser (Y160S) substitution at a highly conserved residue, and a c.97C-T transition in exon 2, resulting in a gln33-to-ter (Q33X; 605087.0005) substitution. The Y160S mutation was found in 2 additional patients: patient 5, born of consanguineous Egyptian parents, was homozygous for Y160S, whereas patient 4, born of unrelated Egyptian parents, was compound heterozygous for Y160S and a G-to-C transversion (c.94-1G-C; 605087.0006). None of the patients had seizures. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. None were found in the homozygous state in the gnomAD database. Neither Q33X nor the splice site mutation were in gnomAD, whereas Y160S was found at a low frequency. Blood cells derived from patient 3 showed decreased expression of GPI-anchored proteins.