A novel mutation in LPAR6 causes autosomal recessive hypotrichosis of the scalp.
BACKGROUND
Autosomal recessive hypotrichosis simplex (ARHS) presents with progressive hair loss mainly affecting the scalp area. In a small number of families, the condition has been associated with mutations in three distinct genes: DSG4, LIPH and LPAR6.


OBJECTIVE
To identify the molecular basis of ARHS in a consanguineous family of Turkish extraction.


METHODS
We used a combination of microsatellite marker screening and direct sequencing.


RESULTS
We identified a novel missense mutation (c.C587T) in the human LPAR6 gene, resulting in the amino acid substitution p.P196L. The mutation affects a highly conserved amino acid residue, and is predicted to disrupt signalling through the P2Y5 receptor.


CONCLUSIONS
This study provides further evidence supporting a role for the lysophosphatidyl signalling pathway in hair growth and differentiation. In addition, this paper reports, for the first time to our knowledge, the use of homozygosity mapping as a premutation screening tool in the diagnosis of a group of inherited hair disorders.
Center for Translational Genetics, Rappaport Institute for Research in the Medical Sciences, Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
S
S
Nahum
F
F
Morice-Picard
A
A
Taieb
E
E
Sprecher
D000293:Adolescent; D019943:Amino Acid Substitution; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005838:Genotype; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D020125:Mutation, Missense; D010375:Pedigree; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics*; D012535:Scalp
C545560:LPAR6 protein, human; D049368:Receptors, Lysophosphatidic Acid