Recurrent splice-site mutation in MBTPS2 underlying IFAP syndrome with Olmsted syndrome-like features in a Chinese patient

Summary Mutations in MBTPS2 have been reported to cause a broad phenotypic spectrum ofX-linked genodermatoses, including IFAP (ichthyosis follicularis; atrichia and photo-phobia) syndrome (OMIM 308205) with or without BRESHECK (brain anomalies,retardation of mentality and growth, ectodermal dysplasia, skeletal malformations,Hirschsprung disease, ear deformity and deafness, eye hypoplasia, cleft palate,cryptorchidism, and kidney dysplasia/hypoplasia) syndrome, keratosis follicularisspinulosa decalvans (KFSD; OMIM 308800) and an X-linked form of Olmsted syn-drome. We report a recurrent intronic mutation in MBTPS2 (c.671-9T>G) in aChinese patient with the typical triad of IFAP syndrome (i.e. ichthyosis, atrichiaand photophobia), along with pachyonychia, palmoplantar and periorificial kerato-derma, which were reminiscent of Olmsted syndrome. Interestingly, this mutationwas previously reported in two cases of IFAP without keratoderma, which suggestsclinical heterogeneicity of the same mutation in MBTPS2. The concomitance ofOlmsted syndrome-like features in this patient with IFAP may challenge the exis-tence of the X-linked form of Olmsted syndrome as an independent condition.Mutations in the gene encoding for membrane-boundtranscription factor protease site 2 (MBTPS2) havebeen reported to cause a broad phenotypic spectrum ofX-linked genodermatoses, including IFAP (ichthyosisfollicularis; atrichia and photophobia) syndrome(OMIM 308205) and an X-linked form of Olmsted syn-drome. We report a patient with features of IFAP andother Olmsted syndrome-like conditions.