Please use this identifier to cite or link to this item: doi:10.22028/D291-39813
Title: Genome-wide linkage analysis of families with primary hyperhidrosis
Author(s): Schote, Andrea B
Schiel, Florian
Schmitt, Benedikt
Winnikes, Ulrike
Frank, Nicole
Gross, Katharina
Croyé, Marie-Anne
Tarragon, Ernesto
Bekhit, Adam
Bobbili, Dheeraj Reddy
May, Patrick
Schick, Christoph
Meyer, Jobst
Language: English
Title: PloS one
Volume: 15
Issue: 12
Publisher/Platform: PLOS
Year of Publication: 2020
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Primary focal hyperhidrosis (PFH, OMIM %144110) is a genetically influenced condition characterised by excessive sweating. Prevalence varies between 1.0-6.1% in the general population, dependent on ethnicity. The aetiology of PFH remains unclear but an autosomal dominant mode of inheritance, incomplete penetrance and variable phenotypes have been reported. In our study, nine pedigrees (50 affected, 53 non-affected individuals) were included. Clinical characterisation was performed at the German Hyperhidrosis Centre, Munich, by using physiological and psychological questionnaires. Genome-wide parametric linkage analysis with GeneHunter was performed based on the Illumina genome-wide SNP arrays. Haplotypes were constructed using easyLINKAGE and visualised via HaploPainter. Whole-exome sequencing (WES) with 100x coverage in 31 selected members (24 affected, 7 non-affected) from our pedigrees was achieved by next generation sequencing. We identified four genome-wide significant loci, 1q41-1q42.3, 2p14-2p13.3, 2q21.2-2q23.3 and 15q26.3-15q26.3 for PFH. Three pedigrees map to a shared locus at 2q21.2-2q23.3, with a genome-wide significant LOD score of 3.45. The chromosomal region identified here overlaps with a locus at chromosome 2q22.1-2q31.1 reported previously. Three families support 1q41-1q42.3 (LOD = 3.69), two families share a region identical by descent at 2p14-2p13.3 (LOD = 3.15) and another two families at 15q26.3 (LOD = 3.01). Thus, our results point to considerable genetic heterogeneity. WES did not reveal any causative variants, suggesting that variants or mutations located outside the coding regions might be involved in the molecular pathogenesis of PFH. We suggest a strategy based on whole-genome or targeted next generation sequencing to identify causative genes or variants for PFH.
DOI of the first publication: 10.1371/journal.pone.0244565
URL of the first publication:
Link to this record: urn:nbn:de:bsz:291--ds-398136
ISSN: 1932-6203
Date of registration: 22-May-2023
Faculty: M - Medizinische Fakultät
Department: M - Medizinische Biometrie, Epidemiologie und medizinische Informatik
Professorship: M - Prof. Dr. Stefan Wagenpfeil
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

Files for this record:
File Description SizeFormat 
journal.pone.0244565.pdf2 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons