Universität zu Köln

Altmueller, Janine, Haenisch, Britta, Kawalia, Amit, Menzen, Markus, Noethen, Markus M., Fier, Heide and Molderings, Gerhard J. (2017). Mutational profiling in the peripheral blood leukocytes of patients with systemic mast cell activation syndrome using next-generation sequencing. Immunogenetics, 69 (6). S. 359 - 370. NEW YORK: SPRINGER. ISSN 1432-1211

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Abstract

Mast cell activation syndrome (MCAS) and systemic mastocytosis (SM) are two clinical systemic mast cell activation disease variants. Few studies to date have investigated the genetic basis of MCAS. The present study had two aims. First, to investigate whether peripheral blood leukocytes from MCAS patients also harbor somatic mutations in genes implicated in SM using next-generation sequencing (NGS) technology and a relatively large MCAS cohort. We also addressed the question, whether some of the previously as somatic reported mutations are indeed germline mutations. Second, to identify germline mutations of relevance to MCAS pathogenesis. Here, mutation frequency in the present MCAS cohort was compared to that in public- and in-house databases in the case of frequent variants, and co-segregation was investigated in multiply affected families in the case of rare variants (allele frequency < 1%). MCAS diagnoses were assigned according to current criteria. Twenty five candidate genes were selected on the basis of published findings for SM. NGS was performed using a 76kbp custom designed Agilent SureSelect Target Enrichment and an Illumina Hiseq2000 2x100bp sequencing run. NGS revealed 67 germline mutations. No somatic mutations were detected. None of the germline mutations showed unequivocal association with MCAS. Failure to detect somatic mutations was probably attributable to the dilution of mutated mast cell DNA in normal leukocyte DNA. The present exploratory association findings suggest that some of the detected germline mutations may be functionally relevant and explain familial aggregation. Independent replication studies are therefore warranted.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Haenisch, Britta UNSPECIFIED UNSPECIFIED UNSPECIFIED Kawalia, Amit UNSPECIFIED UNSPECIFIED UNSPECIFIED Menzen, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Noethen, Markus M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fier, Heide UNSPECIFIED UNSPECIFIED UNSPECIFIED Molderings, Gerhard J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-229421
DOI:	10.1007/s00251-017-0981-y
Journal or Publication Title:	Immunogenetics
Volume:	69
Number:	6
Page Range:	S. 359 - 370
Date:	2017
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-1211
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENOME-WIDE ASSOCIATION; CATALYTIC DOMAIN; TYROSINE KINASE; BREAST-CANCER; C-KIT; MASTOCYTOSIS; DISEASE; DISORDERS; VARIANTS; FORMS Multiple languages Genetics & Heredity; Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22942