For discussion of the 1-bp deletion (c.456delA, NM_153681.2) in the PIGP gene, resulting in a frameshift and premature termination (Glu153AsnfsTer34), that was found in compound heterozygous state in 2 sibs with developmental and epileptic encephalopathy-55 (DEE55; 617599) by Johnstone et al. (2017), see 605938.0001.
In a 2-year-old girl, born of unrelated Polish parents, with DEE55, Krenn et al. (2019) identified homozygosity for the c.456delA mutation in the PIGP gene. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was found at low frequencies in only heterozygous state in an in-house database (6 in over 16,000 exomes) and gnomAD (9 exomes). Flow cytometric analysis of patient lymphocytes showed decreased expression of GPI-anchored proteins, suggesting a loss-of-function effect. The findings confirmed PIGP as a monogenic disease causing developmental and epileptic encephalopathy. The patient had onset of refractory focal seizures at 7 months of age. Developmental milestones were not reached.
In 4 affected individuals from a large consanguineous kindred with DEE55, Vetro et al. (2020) identified a homozygous 1-bp deletion (c.384del, NM_153682.2) in the PIGP gene, predicted to result in a frameshift and premature termination (Glu129AsnfsTer34). The authors stated that this was the same mutation as that reported by Krenn et al. (2019). The mutation identified by Vetro et al. (2020) was found by exome sequencing and confirmed by Sanger sequencing. It segregated with the disorder in the family and was found at a low frequency in the gnomAD database (3 x 10(-5)). Flow cytometric analysis of patient lymphocytes showed decreased levels of the GPI-anchored protein CD16 (146740) and mildly decreased levels of CD24 (600074), whereas expression of another GPI-anchored protein, CD55 (125240), was normal. The patients had onset of refractory focal and generalized seizures at 3 months of age. EEG showed burst-suppression pattern. The patients achieved almost no developmental milestones; 2 died at 12 years and 27 months, respectively.
