Identification of three novel mutations of the noggin gene in patients with fibrodysplasia ossificans progressiva

We report noggin mutations in three Spanish families with fibrodysplasia os sificans progressiva (FOP). The three propositi have typical FOP findings; in the first and third families the parents are unaffected, while in the se cond family the father is partially affected. DNA of the three propositi an d their parents was screened by sequencing for mutations in the noggin gene (NOG). Sequencing indicated a G to C mutation at nucleotide 274 of the NOG gene in the first propositus, encoding for the G92R substitution at the pe ptide level; this first mutation is de novo, the corresponding change not b eing observed in parents. In the second propositus, a G to T mutation at nu cleotide 271 encodes for the G91C substitution, transmitted in the correspo nding family by the partially affected father. In the third propositus, seq uencing indicated a Gr to A mutation at nucleotide 275, encoding for the G9 2E substitution; this third mutation is de novo. All three mutations, as we ll as the Delta 42 deletion already reported, resulted in the alteration of the portion of the NOG gene at positions 265-282, encoding for the potenti al N-myristoylation site at residues 89-GGGGGA-94. (C) 2001 Wiley-Liss, Inc .