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A novel mutation in PIGW causes glycosylphosphatidylinositol deficiency without hyperphosphatasia
Author(s) -
Hogrebe Max,
Murakami Yoshiko,
Wild Martin,
Ahlmann Martina,
Biskup Saskia,
Hörtnagel Konstanze,
Grüneberg Marianne,
Reunert Janine,
Linden Tobias,
Kinoshita Taroh,
Marquardt Thorsten
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37950
Subject(s) - flow cytometry , phenotype , mutation , transfection , biology , cd24 , microbiology and biotechnology , genetics , gene
In recent years, many mutations have been identified that affect the biosynthesis of the glycosylphosphatidylinositol anchor, a biomolecule that attaches surface molecules to cell membranes. Here, we present two second‐degree cousins with unexplained patterns of seizures. Next‐generation sequencing identified the homozygous c.460A>G; p.(R154G) PIGW mutation in both patients. Transfection of the mutated allele into Pigw ‐defective CHO cells indicated impaired enzymatic activity of the mutated PIGW product. Alkaline phosphatase did not exceed the upper normal range and flow cytometry of CD16, CD24, and CD66c on granulocytes showed subtle changes of the cellular expression of the glycosylphosphatidylinositol‐anchored proteins. The patients’ phenotype is therefore remarkably different from the phenotype of the only other described individual with PIGW mutations. Patients might therefore be missed when relying on traditional flow cytometry of glycosylphosphatidylinositol‐anchored proteins only and we suggest that glycosylphosphatidylinositol‐deficiency should be considered even with patients not showing the typical clinical phenotypes. © 2016 Wiley Periodicals, Inc.