PIGP – Developmental and Epileptic Encephalopathy 55

PIGP encodes a subunit essential for glycosylphosphatidylinositol-anchor biosynthesis and has been implicated in autosomal recessive Developmental and Epileptic Encephalopathy 55. To date, only a single family with two affected siblings has been reported, both presenting severe hypotonia and early-onset epileptic encephalopathy (HP:0001252, HP:0200134) (PMID:37125481). Whole-exome sequencing identified compound heterozygous variants in PIGP: NM_153682.3:c.2C>T (p.?) and a 136 kb deletion spanning chr21:38329939-38466066; both were absent in population databases (PMID:37125481). Segregation analysis confirmed each parent as a heterozygous carrier, consistent with autosomal recessive inheritance. No functional studies specific to PIGP variants have been reported to date. Overall, genetic evidence remains limited to this single multiplex pedigree, warranting further case series and experimental validation to confirm pathogenicity. Key Take-home: PIGP deficiency should be considered in autosomal recessive DEE with congenital anomalies and hypotonia, but additional evidence is needed to establish definitive clinical validity.

References

• Clinical genetics • 2023 • Expanding the phenotype of PIGP deficiency to multiple congenital anomalies-hypotonia-seizures syndrome. PMID:37125481

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