The intronic variant was predicted to mediate in-frame exon 5 skipping within the serine/threonine kinase (STK) domain, which may also be mediated by a similar TGFBR1 variant of a splice acceptor site in intron 4 (c.806-2 A > C), identified in a British familial case of MSSE.
This distinguishes MSSE from the Marfan syndrome-related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer.
This transcript map encompasses both the HSN-I critical interval and the locus for multiple self-healing squamous epithelioma (MSSE, previously named ESS1).
This XPA polymorphism and nine new polymorphic markers that map in the MSSE region were typed in eleven MSSE families; XPA was excluded as the MSSE gene and the most likely location of MSSE was reduced to the interval between D9S197 and (D9S287, D9S1809).