Keratosis Follicularis Spinulosa Decalvans Is Caused by Mutations in MBTPS2

Keratosis Follicularis Spinulosa Decalvans (KFSD) is a rare genetic disorder characterized by development of hyperkeratotic follicular papules on the scalp followed by progressive alopecia of the scalp, eyelashes, and eyebrows. Associated eye findings include photophobia in childhood and corneal dystrophy. Due to the genetic and clinical heterogeneity of similar disorders, a definitive diagnosis of KFSD is often challenging. Toward identification of the causative gene we reanalyzed a large Dutch KFSD family. SNP arrays (1 M) redefined the locus to a 2.9-Mb region at Xp22.12-Xp22.11. Screening of all 14 genes in the candidate region identified MBTPS2 as the candidate gene carrying a c.1523A>G (p.Asn508Ser) missense mutation. The variant was also identified in two unrelated X-linked KFSD families and cosegregated with KFSD in all families. In symptomatic female carriers, skewed X-inactivation of the normal allele matched with increased severity of symptoms. MBTPS2 is required for cleavage of sterol regulatory element-binding proteins (SREBPs). In vitro functional expression studies of the c. 1523A>G mutation showed that sterol responsiveness was reduced by half. Other missense mutations in MBTPS2 have recently been identified in patients with IFAP syndrome. We postulate that both phenotypes are in the spectrum of one genetic disorder with a partially overlapping phenotype. Hum Mutat 31:1125-1133, 2010. (C) 2010 Wiley-Liss, Inc

Film-Free LIFT (FF-LIFT)

This chapter discusses in detail the current problems related to the preparation of liquid films in laser-induced forward transfer (LIFT), from fundamental aspects to practical problems. It introduces film-free LIFT (FF-LIFT), explains its physical principles, and describes the different modalities in which the technique can be implemented. It discusses important experimental factors that can affect the quality of the printing process, such as spherical aberration or optical absorption of the liquid, and finally, gives examples of applications in which FF-LIFT has been successfully used. The uniformity of the donor film has a direct influence on the outcome of the LIFT printing process. The intrinsic instability of a liquid film and the technical problems associated with the preparation of materials in film form led to the development of a novel laser printing technique capable of depositing a liquid directly from a reservoir