Universität zu Köln

Broekaert, Ilse Julia, Becker, Kerstin, Gottschalk, Ingo, Koerber, Friederike, Doetsch, Joerg, Thiele, Holer, Altmueller, Janine, Nuernberg, Peter, Huenseler, Christoph and Cirak, Sebahattin (2018). Mutations in plasmalemma vesicle-associated protein cause severe syndromic protein-losing enteropathy. J. Med. Genet., 55 (9). S. 637 - 641. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-6244

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Abstract

Background Protein-losing enteropathy (PLE) is characterised by gastrointestinal protein leakage due to loss of mucosal integrity or lymphatic abnormalities. PLE can manifest as congenital diarrhoea and should be differentiated from other congenital diarrhoeal disorders. Primary PLEs are genetically heterogeneous and the underlying genetic defects are currently emerging. Objectives We report an infant with fatal PLE for whom we aimed to uncover the underlying pathogenic mutation. Methods We performed whole exome sequencing (WES) for the index patient. Variants were classified based on the American College of Medical Genetics and Genomics guidelines. WES results and our detailed clinical description of the patient were compared with the literature. Results We discovered a novel homozygous stop mutation (c.988C>T, p.Q330*) in the Plasmalemma Vesicle-Associated Protein (PLVAP) gene in a newborn with fatal PLE, facial dysmorphism, and renal, ocular and cardiac anomalies. The Q330* mutation is predicted to result in complete loss of PLVAP protein expression leading to deletion of the diaphragms of endothelial fenestrae, resulting in plasma protein extravasation and PLE. Recently, another single homozygous stop mutation in PLVAP causing lethal PLE in an infant was reported. Conclusions Our findings validate PLVAP mutations as a cause of syndromic PLE. Prenatal anomalies, severe PLE and syndromic features may guide the diagnosis of this rare disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Broekaert, Ilse Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Gottschalk, Ingo UNSPECIFIED UNSPECIFIED UNSPECIFIED Koerber, Friederike UNSPECIFIED UNSPECIFIED UNSPECIFIED Doetsch, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holer UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Huenseler, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Cirak, Sebahattin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-173440
DOI:	10.1136/jmedgenet-2018-105262
Journal or Publication Title:	J. Med. Genet.
Volume:	55
Number:	9
Page Range:	S. 637 - 641
Date:	2018
Publisher:	BMJ PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1468-6244
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DGAT1 MUTATION; VARIANTS; A2ML1; PV-1 Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17344