A novel locus for alopecia with mental retardation syndrome (APMR2) maps to chromosome 3q26.2-q26.31

Abstract

Congenital alopecia may occur either alone or in association with ectodermal and other abnormalities. On the bases of such associations, several different syndromes featuring congenital alopecia can be distinguished. Alopecia with mental retardation syndrome (APMR) is a rare autosomal recessive disorder, clinically characterized by total or partial hair loss and mental retardation. In the present study, a five-generation Pakistani family with multiple affected individuals with APMR was ascertained. Patients in this family exhibited typical features of APMR syndrome. The disease locus was mapped to chromosome 3q26.2-q26.31 by carrying out a genome scan followed by fine mapping. A maximum two-point logarithm of odds (LOD) score of 2.93 at theta=0.0 was obtained at markers D3S3053 and D3S2309. Multipoint linkage analysis resulted in a maximum LOD score of 4.57 with several markers, which supports the linkage. The disease locus was flanked by markers D3S1564 and D3S2427, which corresponds to 9.6-cM region according to the Rutgers combined linkage-physical map of the human genome (build 35) and contains 5.6 Mb. The linkage interval of the APMR locus identified here does not overlap with the one described previously; therefore, this locus has been designated as APMR2.

Fig. 1.

Drawing of pedigree that segregates APMR2. Filled symbols represent affected individuals. Clear symbols represent unaffected individuals. Map distances are given in centimorgans (cM) according to the Rutgers linkage-physical map of the human genome. The disease-associated haplotypes are shown beneath each symbol. Haplotypes were generated by SIMWALK2.

Fig. 2.

Clinical presentation of APMR2 family. (a) Phenotypic appearance of affected individual V-3 showing complete absence of hair on scalp and missing eyebrows and eyelashes. (b) Complete absence of hair on scalp of affected female V-4 with no eyebrows and eyelashes.

Fig. 3.

Comparison of the linkage interval of AH, APMR and APMR2 on chromosome 3q26 region. Genetic map distances in centimorgans (cM) are according to the Rutgers linkage-physical map of the human genome (20).