Universität zu Köln

Knaus, Alexej, Awaya, Tomonari, Helbig, Ingo ORCID: 0000-0001-8486-0558, Afawi, Zaid, Pendziwiat, Manuela, Abu-Rachma, Jubran, Thompson, Miles D., Cole, David E., Skinner, Steve, Annese, Fran, Canham, Natalie, Schweiger, Michal R., Robinson, Peter N., Mundlos, Stefan, Kinoshita, Taroh, Munnich, Arnold, Murakami, Yoshiko, Horn, Denise and Krawitz, Peter M. (2016). Rare Noncoding Mutations Extend the Mutational Spectrum in the PGAP3 Subtype of Hyperphosphatasia with Mental Retardation Syndrome. Hum. Mutat., 37 (8). S. 737 - 745. HOBOKEN: WILEY-BLACKWELL. ISSN 1098-1004

Full text not available from this repository.

Abstract

HPMRS or Mabry syndrome is a heterogeneous glycosylphosphatidylinositol (GPI) anchor deficiency that is caused by an impairment of synthesis or maturation of the GPI-anchor. The expressivity of the clinical features in HPMRS varies from severe syndromic forms with multiple organ malformations to mild nonsyndromic intellectual disability. In about half of the patients with the clinical diagnosis of HPMRS, pathogenic mutations can be identified in the coding region in one of the six genes, one among them is PGAP3. In this work, we describe a screening approach with sequence specific baits for transcripts of genes of the GPI pathway that allows the detection of functionally relevant mutations also including introns and the 5 and 3 UTR. By this means, we also identified pathogenic noncoding mutations, which increases the diagnostic yield for HPMRS on the basis of intellectual disability and elevated serum alkaline phosphatase. In eight affected individuals from different ethnicities, we found seven novel pathogenic mutations in PGAP3. Besides five missense mutations, we identified an intronic mutation, c.558-10G>A, that causes an aberrant splice product and a mutation in the 3UTR, c.*559C>T, that is associated with substantially lower mRNA levels. We show that our novel screening approach is a useful rapid detection tool for alterations in genes coding for key components of the GPI pathway.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Knaus, Alexej UNSPECIFIED UNSPECIFIED UNSPECIFIED Awaya, Tomonari UNSPECIFIED UNSPECIFIED UNSPECIFIED Helbig, Ingo UNSPECIFIED orcid.org/0000-0001-8486-0558 UNSPECIFIED Afawi, Zaid UNSPECIFIED UNSPECIFIED UNSPECIFIED Pendziwiat, Manuela UNSPECIFIED UNSPECIFIED UNSPECIFIED Abu-Rachma, Jubran UNSPECIFIED UNSPECIFIED UNSPECIFIED Thompson, Miles D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cole, David E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Skinner, Steve UNSPECIFIED UNSPECIFIED UNSPECIFIED Annese, Fran UNSPECIFIED UNSPECIFIED UNSPECIFIED Canham, Natalie UNSPECIFIED UNSPECIFIED UNSPECIFIED Schweiger, Michal R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Robinson, Peter N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mundlos, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Kinoshita, Taroh UNSPECIFIED UNSPECIFIED UNSPECIFIED Munnich, Arnold UNSPECIFIED UNSPECIFIED UNSPECIFIED Murakami, Yoshiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Horn, Denise UNSPECIFIED UNSPECIFIED UNSPECIFIED Krawitz, Peter M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-268506
DOI:	10.1002/humu.23006
Journal or Publication Title:	Hum. Mutat.
Volume:	37
Number:	8
Page Range:	S. 737 - 745
Date:	2016
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	1098-1004
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GPI-ANCHORED PROTEINS; SYNTHESIS PATHWAY; PIGV MUTATIONS; DEFICIENCY; SEIZURES Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26850