A de novo heterozygous deletion of 42 base‐pairs in the noggin gene of a fibrodysplasia ossificansprogressiva patient

Reported noggin mutations are PCR errors

“…Our findings strongly suggest that the reported mutations of Semonin et al [2001] and of Lucotte et al [1999] are PCR errors as described in our recent study on the subject [Xu et al, 2000]. The reason for the differences in data between Dr. Lucotte's studies and others, we believe, is technical: the authors (as described to us personally by Dr. Lucotte) used nested PCR reactions in order to amplify the noggin sequence and then cloned and sequenced individual PCR products.…”

“…As importantly, in the AJMG paper, the authors discuss a 42 bp in-frame deletion in the noggin gene in a patient reported previously [Lucotte et al, 1999]. They failed, however, to accurately discuss the critical finding that was described in our study published recently [Xu et al, 2000]: specifically the inability to confirm the purported deletion in a DNA sample obtained independently from the identical individual they have reported.…”

Bone morphogenetic proteins with some comments on fibrodysplasia ossificans progressiva and NOGGIN

“…SYNS1 mutations are characterized by synostosis of the interphalangeal joints together with abnormalities of the cervical spine and hips [Gong et al, 1999]. Lucotte et al [1999] and Sémonin et al [2001] reported NOG mutations for FOP. However, these are probably PCR errors, as noted by Xu et al [2000].…”

“…However, these are probably PCR errors, as noted by Xu et al [2000]. The FOP patient with the D42G260-C301 mutation reported by Lucotte et al [1999] was examined independently by the International FOP Research Consortium who failed to detect the presence of the reported 42-bp deletion [see Xu et al, 2000]. NOG is an unusual gene.…”

Significant difference of opinion regarding the role of noggin in fibrodysplasia ossificans progressiva

“…The authors mention, but do not discuss, the difference of opinion within the literature regarding the role of noggin (NOG) in FOP. Lucotte and colleagues [2000] have reported linkage between NOG and FOP, and have found putative disease-causing NOG mutations in several patients [Lucotte et al, 1999;Semonin et al, 2001]. However, another group has excluded linkage between NOG and FOP and failed to find disease-causing mutations among their patients [Xu et al, 2000].…”