Autosomal-dominant hypotrichosis with woolly hair: Novel gene locus on chromosome 4q35.1-q35.2

Autoři: Annika E. Schlaweck aff001;  Rachid Tazi-Ahnini aff002;  F. Buket Ü. Basmanav aff001;  Javed Mohungoo aff003;  Sandra M. Pasternack-Ziach aff001;  Manuel Mattheisen aff004;  Ana-Maria Oprisoreanu aff005;  Aytaj Humbatova aff001;  Sabrina Wolf aff001;  Andrew Messenger aff003;  Regina C. Betz aff001
Působiště autorů: Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany aff001;  Department of Infection, Immunity, and Cardiovascular Disease, The Medical School, University of Sheffield, Sheffield, United Kingdom aff002;  Department of Dermatology, Royal Hallamshire Hospital, Sheffield, United Kingdom aff003;  Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital Würzburg, Würzburg, Germany aff004;  Department of Neuropathology and Department of Epileptology, University Hospital Bonn, Bonn, Germany aff005
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article


Hypotrichosis simplex (HS) with and without woolly hair (WH) comprises a group of rare, monogenic disorders of hair loss. Patients present with a diffuse loss of scalp and/or body hair, which usually begins in early childhood and progresses into adulthood. Some of the patients also show hair that is tightly curled. Approximately 10 genes for autosomal recessive and autosomal dominant forms of HS have been identified in the last decade, among them five genes for the dominant form. We collected blood and buccal samples from 17 individuals of a large British family with HS and WH. After having sequenced all known dominant genes for HS in this family without the identification of any disease causing mutation, we performed a genome-wide scan, using the HumanLinkage-24 BeadChip, followed by a classical linkage analysis; and whole exome-sequencing (WES). Evidence for linkage was found for a region on chromosome 4q35.1-q35.2 with a maximum LOD score of 3.61. WES led to the identification of a mutation in the gene SORBS2, encoding sorbin and SH3 domain containing 2. Unfortunately, we could not find an additional mutation in any other patient/family with HS; and in cell culture, we could not observe any difference between cloned wildtype and mutant SORBS2 using western blotting and immunofluorescence analyses. Therefore, at present, SORBS2 cannot be considered a definite disease gene for this phenotype. However, the locus on chromosome 4q is a robust and novel finding for hypotrichosis with woolly hair. Further fine mapping and sequencing efforts are therefore warranted in order to confirm SORBS2 as a plausible HS disease gene.

Klíčová slova:

Cytoskeletal proteins – Cytoskeleton – Gene sequencing – Genetic loci – Hair – Immunofluorescence – Linkage analysis – Scalp


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2019 Číslo 12
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