B4.5 A Gene Locus Responsible For Pili Annulati Maps To Chromosome 12q24.32-24.33

Kathrin A Giehl¹, Gertrud Eckstein², Anna Benet-Pages², Antonella Tosti³, David AR de Berker⁴, Thomas Meitinger^2,6, Bertram Müller-Myhsok⁵, Tim M Strom^2,6

¹Department of Dermatology, Ludwig-Maximilians University, Munich, Germany. ²Institute of Human Genetics, GSF National Research Center, Munich-Neuherberg, Germany. ³Department of Dermatology, University of Bologna, Bologna, Italy. ⁴Bristol Dermatology Centre, Bristol Royal Infirmary, Bristol, U.K. ⁵Max-Planck-Institute of Psychiatry, Munich, Germany. ⁶Institute of Human Genetics, Technical University, Munich, Germany.

The purpose of this study was to investigate the genetic cause of pili annulati, a rare familial autosomal dominant inherited hair shaft abnormality. Pili annulati is characterised by alternating light and dark bands of the hair shaft leading to a speckled shiny appearance.

Genomic DNA was extracted from thirty-nine individuals of five families, after they were examined and had their hair taken for light microscopy to establish their phenotype.

A genome-wide linkage analysis using 382 microsatellite markers was performed in nineteen affected and eleven unaffected individuals of five families. An additional one affected and six unaffected individuals were included for fine mapping. In two individuals a definite phenotype could not be determined.

Initial evidence for linkage of pili annulati was obtained at the telomeric part of the long arm of chromosome 12. For finemapping, seven additional microsatellite markers spanning the 20 cM region of significance were analysed. Linkage analysis was performed assuming an autosomal dominant inheritance with 95% penetrance. The maximum multipoint LOD score was 3.24 at D12S1723 under assumption of homogeneity and 3.57 around D12S343 under the assumption of heterogeneity. Both LOD scores were beyond the respective thresholds necessary to conclude for linkage, therefore establishing linkage to chromosome 12q24.32-24.33. Most of this LOD score came from the largest family that reached a maximum multipoint LOD score of 3.81. The maximum two-point LOD score for all families was 4.64 at D121609. Definite recombination events narrowed the region of shared haplotype in affected individuals to an eight Mb region between the marker D12S324 and the telomeric end of the long arm of chromosome 12.

In summary, we performed a genomwide linkage analysis in five pedigrees and established linkage to a 20 cM interval on chromosome 12q24.32-24.33.