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Keratosis Follicularis Spinulosa Decalvans is caused by mutations in MBTPS2.
Hum Mutat 2010; 31(10):1125-33HM

Abstract

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.

Authors+Show Affiliations

Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Nederlands. E.Aten@lumc.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20672378

Citation

Aten, Emmelien, et al. "Keratosis Follicularis Spinulosa Decalvans Is Caused By Mutations in MBTPS2." Human Mutation, vol. 31, no. 10, 2010, pp. 1125-33.
Aten E, Brasz LC, Bornholdt D, et al. Keratosis Follicularis Spinulosa Decalvans is caused by mutations in MBTPS2. Hum Mutat. 2010;31(10):1125-33.
Aten, E., Brasz, L. C., Bornholdt, D., Hooijkaas, I. B., Porteous, M. E., Sybert, V. P., ... den Dunnen, J. T. (2010). Keratosis Follicularis Spinulosa Decalvans is caused by mutations in MBTPS2. Human Mutation, 31(10), pp. 1125-33. doi:10.1002/humu.21335.
Aten E, et al. Keratosis Follicularis Spinulosa Decalvans Is Caused By Mutations in MBTPS2. Hum Mutat. 2010;31(10):1125-33. PubMed PMID: 20672378.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Keratosis Follicularis Spinulosa Decalvans is caused by mutations in MBTPS2. AU - Aten,Emmelien, AU - Brasz,Lisa C, AU - Bornholdt,Dorothea, AU - Hooijkaas,Ingeborg B, AU - Porteous,Mary E, AU - Sybert,Virginia P, AU - Vermeer,Maarten H, AU - Vossen,Rolf H A M, AU - van der Wielen,Michiel J R, AU - Bakker,Egbert, AU - Breuning,Martijn H, AU - Grzeschik,Karl-Heinz, AU - Oosterwijk,Jan C, AU - den Dunnen,Johan T, PY - 2010/7/31/entrez PY - 2010/7/31/pubmed PY - 2011/2/1/medline SP - 1125 EP - 33 JF - Human mutation JO - Hum. Mutat. VL - 31 IS - 10 N2 - 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. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/20672378/Keratosis_Follicularis_Spinulosa_Decalvans_is_caused_by_mutations_in_MBTPS2_ L2 - https://doi.org/10.1002/humu.21335 DB - PRIME DP - Unbound Medicine ER -