Cloning, genomic organization, alternative transcripts and mutational analysis of the gene responsible for autosomal recessive universal congenital alopecia

Sven Cichon, Martina Anker, Ina R. Vogt, Hendrik Rohleder, Markus Pützstück, Axel Hillmer, Sardar A. Farooq, Khamis S. Al-Dhafri, Mahmud Ahmad, Sayedul Haque, Marcella Rietschel, Peter Propping, Roland Kruse, Markus M. Nöthen

Research output: Contribution to journalArticle

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Abstract

Complete or partial congenital absence of hair (congenital alopecia) may occur isolated or with associated defects. The majority of families with isolated congenital alopecia has been reported to follow an autosomal recessive mode of inheritance (MIM 203655). We have previously mapped the gene for autosomal recessive congenital alopecia in a large inbred Pakistani family in which affected persons show complete absence of hair development (universal congenital alopecia) to a 15 cM region on chromosome 8p21-22. Here we report the cloning and characterization of the human homologue of the mouse hairless gene and show that it is located in the critical region on chromosome 8p21-22. Determining the exon-intron structure allowed detailed mutational analysis of DNA samples of patients with universal congenital alopecia. We detected a homozygous missense mutation in the Pakistani family and a homozygous splice donor mutation in a family from Oman. In addition, we show that the human hairless gene undergoes alternative splicing and that at least two isoforms generated by alternative usage of exon 17 are found in human tissues. Interestingly, the isoform containing exon 17 is the predominantly expressed isoform in all tissues but skin, where exclusive expression of the shorter isoform was observed. We speculate that this tissue-specific difference in the proportion of hairless transcripts lacking exon 17 sequences could contribute to the tissue-specific disease phenotype observed in individuals with isolated congenital alopecia.

Original languageEnglish
Pages (from-to)1671-1679
Number of pages9
JournalHuman Molecular Genetics
Volume7
Issue number11
DOIs
Publication statusPublished - Oct 1998

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Organism Cloning
Exons
Protein Isoforms
Genes
Chromosomes, Human, Pair 22
Hair
DNA Mutational Analysis
Oman
Recessive Genes
Hairless Mouse
Alternative Splicing
Missense Mutation
Introns
Congenital alopecia X-linked
Tissue Donors
Phenotype
Skin
Mutation

ASJC Scopus subject areas

  • Genetics

Cite this

Cloning, genomic organization, alternative transcripts and mutational analysis of the gene responsible for autosomal recessive universal congenital alopecia. / Cichon, Sven; Anker, Martina; Vogt, Ina R.; Rohleder, Hendrik; Pützstück, Markus; Hillmer, Axel; Farooq, Sardar A.; Al-Dhafri, Khamis S.; Ahmad, Mahmud; Haque, Sayedul; Rietschel, Marcella; Propping, Peter; Kruse, Roland; Nöthen, Markus M.

In: Human Molecular Genetics, Vol. 7, No. 11, 10.1998, p. 1671-1679.

Research output: Contribution to journalArticle

Cichon, S, Anker, M, Vogt, IR, Rohleder, H, Pützstück, M, Hillmer, A, Farooq, SA, Al-Dhafri, KS, Ahmad, M, Haque, S, Rietschel, M, Propping, P, Kruse, R & Nöthen, MM 1998, 'Cloning, genomic organization, alternative transcripts and mutational analysis of the gene responsible for autosomal recessive universal congenital alopecia', Human Molecular Genetics, vol. 7, no. 11, pp. 1671-1679. https://doi.org/10.1093/hmg/7.11.1671
Cichon, Sven ; Anker, Martina ; Vogt, Ina R. ; Rohleder, Hendrik ; Pützstück, Markus ; Hillmer, Axel ; Farooq, Sardar A. ; Al-Dhafri, Khamis S. ; Ahmad, Mahmud ; Haque, Sayedul ; Rietschel, Marcella ; Propping, Peter ; Kruse, Roland ; Nöthen, Markus M. / Cloning, genomic organization, alternative transcripts and mutational analysis of the gene responsible for autosomal recessive universal congenital alopecia. In: Human Molecular Genetics. 1998 ; Vol. 7, No. 11. pp. 1671-1679.
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