Universität zu Köln

Malki, Liron, Sarig, Ofer, Cesarato, Nicole, Mohamad, Janan, Canter, Talia, Assaf, Sari, Pavlovsky, Mor, Vodo, Dan, Anis, Yossi, Bihari, Ofer, Malovitski, Kiril, Gat, Andrea, Thiele, Holger ORCID: 0000-0002-0169-998X, White, Bethany E. Perez, Samuelov, Liat, Nanda, Arti, Paller, Amy S., Betz, Regina C. and Sprecher, Eli (2020). Loss-of-function variants in C3ORF52 result in localized autosomal recessive hypotrichosis. Genet. Med., 22 (7). S. 1227 - 1235. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1530-0366

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Abstract

Purpose Localized autosomal recessive hypotrichosis (LAH) has been associated with pathogenic variants in DSG4, encoding a desmosomal protein as well as in LIPH and LPAR6, encoding respectively lipase H, which catalyzes the formation of 2-acyl-lysophosphatidic acid (LPA), and lysophosphatidic acid receptor 6, a receptor for LPA. LPA promotes hair growth and differentiation. In this study we aimed at delineating the genetic basis of LAH in patients without pathogenic variants in these three genes. Methods Variant analysis was conducted using exome and direct sequencing. We then performed quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunofluorescence staining, immunoblotting, enzymatic, and coimmunoprecipitation assays to evaluate the consequences of potential etiologic variants. Results We identified homozygous variants in C3ORF52 in four individuals with LAH. C3ORF52 was found to be coexpressed with lipase H in the inner root sheath of the hair follicle and the two proteins were found to directly interact. The LAH-causing variants were associated with decreased C3ORF52 expression and resulted in markedly reduced lipase H-mediated LPA biosynthesis. Conclusion LAH can be caused by abnormal function of at least three proteins which are necessary for proper LPA biosynthesis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Malki, Liron UNSPECIFIED UNSPECIFIED UNSPECIFIED Sarig, Ofer UNSPECIFIED UNSPECIFIED UNSPECIFIED Cesarato, Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED Mohamad, Janan UNSPECIFIED UNSPECIFIED UNSPECIFIED Canter, Talia UNSPECIFIED UNSPECIFIED UNSPECIFIED Assaf, Sari UNSPECIFIED UNSPECIFIED UNSPECIFIED Pavlovsky, Mor UNSPECIFIED UNSPECIFIED UNSPECIFIED Vodo, Dan UNSPECIFIED UNSPECIFIED UNSPECIFIED Anis, Yossi UNSPECIFIED UNSPECIFIED UNSPECIFIED Bihari, Ofer UNSPECIFIED UNSPECIFIED UNSPECIFIED Malovitski, Kiril UNSPECIFIED UNSPECIFIED UNSPECIFIED Gat, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED orcid.org/0000-0002-0169-998X UNSPECIFIED White, Bethany E. Perez UNSPECIFIED UNSPECIFIED UNSPECIFIED Samuelov, Liat UNSPECIFIED UNSPECIFIED UNSPECIFIED Nanda, Arti UNSPECIFIED UNSPECIFIED UNSPECIFIED Paller, Amy S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Betz, Regina C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sprecher, Eli UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-336410
DOI:	10.1038/s41436-020-0794-5
Journal or Publication Title:	Genet. Med.
Volume:	22
Number:	7
Page Range:	S. 1227 - 1235
Date:	2020
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1530-0366
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROTEIN-COUPLED RECEPTOR; PHOSPHATIDIC-ACID; HAIR COUNT; MUTATIONS; INTEGRATION; INCREASES; ALOPECIA; SCALP; LPA Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33641