Just et al. (1998) reported a large 4-generation Spanish family in which 8 affected members had hypotrichosis involving the scalp, eyebrows, and eyelashes, as we...
Just et al. (1998) reported a large 4-generation Spanish family in which 8 affected members had hypotrichosis involving the scalp, eyebrows, and eyelashes, as well as axillary and body hair, but sparing the pubic hair. The hair, when present, was fair and of fine texture. There was variable severity of hypotrichosis among the affected members, with the 4-year-old proband and his 32-year-old mother having diffuse absence of scalp hair with scant eyelashes and eyebrows, whereas the proband's 2 cousins had total absence of hair since birth. The scalp, teeth, and nails showed no visible pathology, intelligence was normal, and there were no other associated anomalies. Hair plucked from 2 affected individuals showed no detectable alteration under light or scanning microscopy, and histologic examination of a scalp biopsy from 1 of the alopecic cousins showed follicles of vellus type.
After excluding 7 loci known to be associated with hypotrichosis or alopecia in the Spanish family segregating autosomal dominant hypotrichosis reported by Just et al. (1998), Pasternack et al. (2013) performed genomewide linkage analysis and found evidence for linkage to chromosome 1q, obtaining a maximum lod score of 2.3 at D1S1660 (theta = 0). Genotyping of additional markers narrowed the candidate region to 21 Mbp, between D1S408 and D1S2141.
▼ Molecular Genetics
In the Spanish family with autosomal dominant hypotrichosis reported by Just et al. (1998), Pasternack et al. (2013) excluded 60 genes on chromosome 1q31-q34 by direct sequencing and then identified heterozygosity for a mutation in the start codon of SNRPE (128260.0001) that segregated with the disease. By sequencing SNRPE in additional patients in a hypotrichosis cohort, they detected the same mutation in a British girl, and also identified a missense mutation in a Tunisian patient (G45S; 128260.0002). Neither mutation was found in 880 German control chromosomes or 598 Spanish control chromosomes, and neither was present in the dbSNP or 1000 Genomes Project databases.