Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0424605 (developmental delay)
 8,158 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Developmental and epileptic encephalopathies are characterized by infantile seizures and psychomotor delay. Glycosylphosphatidylinositol biosynthesis defects, resulting in impaired tethering of various proteins to the cell surface, represent the underlying pathology in some patients. One of the genes involved, PIGP, has recently been associated with infantile seizures and developmental delay in two siblings. Here, we report the second family with a markedly overlapping phenotype due to a homozygous frameshift mutation (c.456delA;p.Glu153Asnfs*34) in PIGP. Flow cytometry of patient granulocytes confirmed reduced expression of glycosylphosphatidylinositol-anchored proteins as functional consequence. Our findings corroborate PIGP as a monogenic disease gene for developmental and epileptic encephalopathy.
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PMID:Biallelic mutations in PIGP cause developmental and epileptic encephalopathy. 3113 95

PIGC (OMIM 601730) encodes the PIGC protein, which is part of an enzyme complex involved in the biosynthesis of the glycosylphosphatidylinositol protein anchor. The other proteins in the complex include PIGA, PIGH, PIGQ, PIGY, PIGP and DPM2. Homozygous and compound heterozygous mutations in PIGC have recently been described to cause severe global developmental delay, intellectual disability, and seizures in two unrelated families, without indication of another system involvement or dysmorphism. Here we describe two siblings, born to second cousin parents, displaying severe psychomotor delay, seizures, organomegaly, cardiopulmonary anomalies, and similar facial dysmorphism. Exome sequencing in the boy revealed a homozygous variant in PIGC gene, c.12_13insTTGTGACTAACA leading to a premature stop codon p.(Gln4_Pro5insLeu*). His affected sister was also found to be homozygous, and their parents were found to be heterozygous. This is the first detailed clinical description of two related patients suggesting that PIGC deficiency can cause a severe recognisable phenotype including multisystem disorders, in association to previously reported severe developmental delay and seizures.
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PMID:Multisystem disorders, severe developmental delay and seizures in two affected siblings, expanding the phenotype of PIGC deficiency. 3270 68