Molecular genetic analysis of two families with keratosis follicularis spinulosa decalvans: refinement of gene localization and evidence for genetic heterogeneity

Abstract

X-linked keratosis follicularis spinulosa decalvans (KFSD) is a rare disorder affecting both skin and eyes. In the two extended KFSD families analysed to date, the gene was mapped to Xp22.13-p22.2. By analyzing several new markers in this region, we were able to narrow the candidate region to a 1-Mb interval between DXS7161 and (DXS7593, DXS7105) in the large Dutch pedigree. In addition, we analyzed 23 markers in Xp21.2-p22.2 in a German family with KFSD. Haplotype and recombination analysis positioned the KFSD gene in this family most likely outside the candidate region on Xp22.13-p22.2. This finding is suggestive for genetic heterogeneity: in this pedigree there is either another locus on the X-chromosome, or KFSD is transmitted here as an autosomal dominant trait with variable expression.

Keratosis Follicularis Spinulosa Decalvans is caused by mutations in MBTPS2

“…Descendants of an extended Dutch pedigree (Oosterwijk et al, 1992a;Oosterwijk et al, 1992b;Oosterwijk et al, 1995;Oosterwijk et al, 1997) were subject to clinical and molecular analysis. First, to map the locus more accurately we analysed several members of each family using 1M SNP arrays.…”

“…Subsequently, the disease location was narrowed down to Xp22.13-p22.2 (Oosterwijk et al, 1995) and later refined to Xp22.13-p22.11 (Oosterwijk et al, 1997). This locus was confirmed in an X-linked family from the UK (Porteous et al, 1998), but lack of informative crossovers prevented detection of the KFSD gene.…”

“…However inheritance is not always clear and isolated cases and autosomal dominant inheritance (i.e. male-to male transmission) has been described as well (Baden and Byers, 1994;Castori et al, 2009;Kuokkanen, 1971;Oosterwijk et al, 1997). KFSD manifests in infancy or early childhood with thorny keratotic follicular papules, progressive alopecia of the scalp, eyelashes and mainly lateral parts of the eyebrows with variable degrees of inflammatory change.…”

“…Ocular abnormalities such as photophobia in childhood, punctate defects of the cornea, corneal dystrophy and blepharitis are common findings. Hyperkeratosis of elbows, knees, palms and soles as well as nail dystrophy may occur (Oosterwijk et al, 1997;Rand and Baden, 1983; Siemens HW, F o r P e e r R e v i e w #308205), keratosis pilaris atrophicans and atrophoderma vermiculatum. (Oranje et al, 1994).…”

Folliculitis decalvans Associated with Micronychia

“…Molecular genetic studies have to decide whether different genes are responsible for the broad disease spectrum. So far, the gene responsible for KFSD with ophthalmopathy has been mapped to Xp22.13-p22.2 in 2 extended families, and genetic heterogeneity was found in a German family [5].…”