Hypotonia and intellectual disability without dysmorphic features in a patient with PIGN-related disease.

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.

• Authors: Isabelle Thiffault, Britton Zuccarelli, Holly Welsh, Xuan Yuan, Emily Farrow, Lee Zellmer, Neil Miller, Sarah Soden, Ahmed Abdelmoity, Robert A Brodsky, Carol Saunders
• Journal: BMC medical genetics (BMC Med Genet) Vol. 18 Issue 1 Pg. 124 (11 02 2017) ISSN: 1471-2350 [Electronic] England
• PMID: 29096607 (Publication Type: Case Reports, Journal Article)

Chemical References

• PIGN protein, human
• Phosphotransferases

Topics

• Abnormalities, Multiple (genetics)
• Child, Preschool
• DNA Mutational Analysis
• Developmental Disabilities (genetics)
• Epilepsies, Partial (genetics)
• Exome (genetics)
• Genetic Predisposition to Disease (genetics)
• Humans
• Male
• Muscle Hypotonia (genetics)
• Mutation
• Phosphotransferases (genetics)