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

• Main Authors: Isabelle Thiffault (Author), Britton Zuccarelli (Author), Holly Welsh (Author), Xuan Yuan (Author), Emily Farrow (Author), Lee Zellmer (Author), Neil Miller (Author), Sarah Soden (Author), Ahmed Abdelmoity (Author), Robert A. Brodsky (Author), Carol Saunders (Author)
• Format: Book
• Published: BMC, 2017-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

10.1186/s12881-017-0481-9
1471-2350