title: A novel homozygous variant in the dsp gene underlies the first case of non-syndromic form of alopecia.
abstract: Autosomal recessive forms of hair loss (alopecia) disorders have previously been associated with variants in at least five different genes including hairless (HR), desmoglein-4 (DSG4), desmocollin-3 (DSC3), lipase-H (LIPH), and lysophosphatidic acid receptor 6 (LPAR6). Here, we report the first familial case of alopecia resulting from a novel homozygous variant in the DSP gene. Since previous reports indicated the presence of heart abnormalities in patients carrying variants in the DSP gene; therefore, the echocardiographic evaluations of all affected members were performed. The results clearly excluded the presence of any form of heart abnormality in patients of the present family. Human genome scan mapped a disease locus on chromosome 6p25.1-p23, harboring DSP gene. Sequence analysis identified a novel homozygous missense variant [c.1493C > T (p.Pro498Leu)] in the DSP gene as the underlying genetic cause of non-syndromic alopecia in the family. The transition alters the completely conserved Pro498 residue in the SH3 domain of plakin that contributes to the stability and rigidity of this subfamily of spectrin repeats (SRs) containing proteins. Our study strengthens the evidence that hereditary hair loss disorders are genetically heterogeneous and imply that isolated form of alopecia is allelic with cardiocutaneous syndromes.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, Pakistan.|Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology (KUST), Kohat, 26000, Pakistan.
authors.forename: Abid
authors.initials: A
authors.lastname: Jan
authors.affiliation: Center for Genetics and Inherited Diseases, Taibah University Almadinah Almunawarah, Medina, Kingdom of Saudi Arabia.
authors.forename: Sulman
authors.initials: S
authors.lastname: Basit
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia.
authors.forename: Salma M
authors.initials: SM
authors.lastname: Wakil
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia.
authors.forename: Khushnooda
authors.initials: K
authors.lastname: Ramzan
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University (QAU), Islamabad, Pakistan. wahmad@qau.edu.pk.
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D000328:Adult; D000505:Alopecia / Q000235:genetics*; D000595:Amino Acid Sequence; D002675:Child, Preschool; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D051180:Desmoplakins / Q000235:genetics*; D005190:Family; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree
chemical_list: C495294:DSP protein, human; D051180:Desmoplakins
keywords: Desmoplakin gene; Homozygous missense variant; Non-syndromic alopecia; SH3 domain