Familial cicatricial alopecia

Gene: MBTPS2

Green List (high evidence)

MBTPS2 (membrane bound transcription factor peptidase, site 2)
EnsemblGeneIds (GRCh38): ENSG00000012174
EnsemblGeneIds (GRCh37): ENSG00000012174
OMIM: 300294, Gene2Phenotype
MBTPS2 is in 12 panels

2 reviews

Rebecca Foulger (Genomics England curator)

Fong et al., 2012 (PMID:22816986) report a British pedigree with KFSD resulting from the N508S variant in KFSDX. Scarring alopecia is recorded for at least 2 of the (6 affected) family members.
Created: 13 Jul 2017, 2:55 p.m.
Bornholdt et al., 2013 (PMID:23316014) identified the N508S variant in MBTPS2 in an 8-year old Swedish boy with KFSDX.
Created: 13 Jul 2017, 2:55 p.m.
3 unrelated cases of MBTPS2 variants in KFSD patients in PMID:20672378, although scarring alopecia isn't specifically recorded for the tested individuals: In affected members of the original Dutch family with X-linked KFSDX, Aten et al. (2010, PMID:20672378) identified a hemizygous variant in the MBTPS2 gene (N508S). The same variant was identified in 2 additional families with the disorder: 1 from the UK originally described in PMID:8745901, and 1 from the US. Haplotype analysis did not suggest a common ancestor.
Created: 13 Jul 2017, 2:54 p.m.
Keratosis follicularis spinulosa decalvans (KFSD) is an uncommon genodermatosis chiefly characterized by widespread keratosis pilaris, progressive cicatricial alopecia of the scalp, eyebrows, and eyelashes, and an excess of affected males. The disorder results from a single recurrent variant (p.Asn508Ser) in MBTPS2. IFAP syndrome (MIM:308205, also caused by variations in MBTPS2) and KFSD share several features, but differentiation is often made on the nature of the alopecia, in IFAP alopecia is congenital nonscarring, whereas it is progressive in KFSDX with variable degrees of inflammatory change leading to scarring.
Created: 13 Jul 2017, 2:54 p.m.
Comment when marking as ready: Marked MBTPS2 as ready: July 3rd 2017.
Created: 3 Jul 2017, 2:18 p.m.
Comment on list classification: Updated rating from Red to Green: 1 Green expert review from Prof. John McGrath. Plus 5 unrelated cases of MBTPS2 N508S variant causing KFSD, which often includes progressive scarring alopecia. Although all KFSD cases so far are caused by the same N508S variant, the cases are unrelated (supported by haplotype analysis).
Created: 3 Jul 2017, 1:47 p.m.

John McGrath (KCL)

Green List (high evidence)

This gene is mutated in the X-linked disorder, keratosis follicularis spinulosa decalvans (KFSD), which is alleleic to ichthyosis follicularis atrichia and photophobia (IFAP). Gene is on the X-chromosome with different male/female implications due to Lyonization.
Created: 22 Jun 2017, 2:59 p.m.

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Keratosis follicularis spinulosa decalvans, X-linked, 208800 (includes progressive cicatricial alopecia of the scalp)
  • KFSDX
  • scarring alopecia
OMIM
300294
Clinvar variants
Variants in MBTPS2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

20 Jul 2017, Gel status: 4

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

20 July 2017: Reviews from Prof. John McGrath were assessed, and panel was revised largely to reflect his expert review. Demoted FOXN1 and GJA1 to grey because the congenital alopecia phenotype is too broad for this cicatricial (scarring) alopecia panel. For most of the red genes, there is only very minor (often indirect) evidence to support a link to cicatricial alopecia, but they remain on the panel, for now, for completeness.

3 Jul 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

3 Jul 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

3 Jul 2017, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for MBTPS2 were set to 22816986; 20672378; 23316014

3 Jul 2017, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for MBTPS2 were set to Keratosis follicularis spinulosa decalvans, X-linked, 208800 (includes progressive cicatricial alopecia of the scalp); KFSDX; scarring alopecia;

22 Nov 2016, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

MBTPS2 was added to Familial cicatricial alopeciapanel. Sources: Other

22 Nov 2016, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

MBTPS2 was created by rfoulger