Document Type
Article
Publication Date
11-2-2017
Identifier
DOI: 10.1186/s12881-017-0481-9
Abstract
BACKGROUND: Defects in the human glycosylphosphatidylinositol anchor biosynthetic pathway are associated with inherited glycosylphosphatidylinositol (GPI)-deficiencies characterized by a broad range of clinical phenotypes including multiple congenital anomalies, dysmorphic faces, developmental delay, hypotonia, and epilepsy. Biallelic variants in PIGN, encoding phosphatidylinositol-glycan biosynthesis class N have been recently associated with multiple congenital anomalies hypotonia seizure syndrome.
CASE PRESENTATION: Our patient is a 2 year old male with hypotonia, global developmental delay, and focal epilepsy. Trio whole-exome sequencing revealed heterozygous variants in PIGN, c.181G > T (p.Glu61*) and c.284G > A (p.Arg95Gln). Analysis of FLAER and anti-CD59 by flow-cytometry demonstrated a shift in this patient's granulocytes, confirming a glycosylphosphatidylinositol-biosynthesis defect, consistent with PIGN-related disease.
CONCLUSIONS: To date, a total of 18 patients have been reported, all but 2 of whom have congenital anomalies and/or obvious dysmorphic features. Our patient has no significant dysmorphic features or multiple congenital anomalies, which is consistent with recent reports linking non-truncating variants with a milder phenotype, highlighting the importance of functional studies in interpreting sequence variants.
Journal Title
BMC medical genetics [electronic resource]
Volume
18
Issue
1
First Page
124
Last Page
124
MeSH Keywords
Abnormalities, Multiple; Child, Preschool; DNA Mutational Analysis; Developmental Disabilities; Epilepsies, Partial; Exome; Genetic Predisposition to Disease; Humans; Male; Muscle Hypotonia; Mutation; Phosphotransferases
Keywords
Developmental disorders; GPI deficiency; Intellectual disability; PIGN; Seizures
Recommended Citation
Thiffault I, Zuccarelli B, Welsh H, et al. Hypotonia and intellectual disability without dysmorphic features in a patient with PIGN-related disease. BMC Med Genet. 2017;18(1):124. Published 2017 Nov 2. doi:10.1186/s12881-017-0481-9
Comments
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Publisher's Link: https://bmcmedgenet.biomedcentral.com/articles/10.1186/s12881-017-0481-9