Universität zu Köln

Neuhofer, Christiane M. ORCID: 0000-0002-5037-4444, Funke, Rudolf, Wilken, Bernd, Knaus, Alexej, Altmueller, Janine, Nuernberg, Peter, Li, Yun, Wollnik, Bernd, Burfeind, Peter and Pauli, Silke (2020). A Novel Mutation in PIGA Associated with Multiple Congenital Anomalies-Hypotonia-Seizure Syndrome 2 (MCAHS2) in a Boy with a Combination of Severe Epilepsy and Gingival Hyperplasia. Mol. Syndromol., 11 (1). S. 30 - 38. BASEL: KARGER. ISSN 1661-8777

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Abstract

Multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2) is a rare disease caused by mutations in the X chromosomal PIGA gene. Clinically it is characterized by early-onset epilepsy, hypotonia, dysmorphic features, and variable congenital anomalies. PIGA codes for the phosphatidylinositol glycan-class A protein, which forms a subunit of an enzymatic complex involved in glycophosphatidylinositol (GPI) biosynthesis. We present a new case of MCAHS2 and perform a comprehensive review of the available literature to delineate the phenotypical traits associated with germline PIGA mutations. Furthermore, we provide functional evidence of pathogenicity of the novel missense mutation, c.154C>T; (p.His52Tyr), in the PIGA gene causative of MCAHS2 in our patient. By flow cytometry, we observed reduced expression of GPI-anchored surface proteins in patient granulocytes compared to control samples, proving GPI-biogenesis impairment. The patient's severe epilepsy with several daily attacks was refractory to treatment, but the frequency of seizures reduced temporarily under triple therapy with perampanel, rufinamide and vigabatrin. Our study delineates the known MCAHS2 phenotype and discusses challenges of diagnosis and clinical management in this complex, rare disease. Furthermore, we present a novel mutation with functional evidence of pathogenicity.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Neuhofer, Christiane M. UNSPECIFIED orcid.org/0000-0002-5037-4444 UNSPECIFIED Funke, Rudolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Wilken, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Knaus, Alexej UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Yun UNSPECIFIED UNSPECIFIED UNSPECIFIED Wollnik, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Burfeind, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Pauli, Silke UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-350974
DOI:	10.1159/000505797
Journal or Publication Title:	Mol. Syndromol.
Volume:	11
Number:	1
Page Range:	S. 30 - 38
Date:	2020
Publisher:	KARGER
Place of Publication:	BASEL
ISSN:	1661-8777
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ALKALINE-PHOSPHATASE; DEVELOPMENTAL DELAY; GERMLINE MUTATION; ENCEPHALOPATHY; FAMILY; PHENOTYPES Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/35097