Reported noggin mutations are PCR errors

Xu, Meiqi; Shore, Eileen M.; Kaplan, Frederick S.

doi:10.1002/ajmg.10288

Cited by 14 publications

(6 citation statements)

References 3 publications

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“…The autosomal dominant inheritance of FOP was first described by Sympson in a case report of a seven-year-old boy with classic features of FOP (6, 7). …”

Section: Discussionmentioning

confidence: 92%

“…FOP usually begins in the first decade of life with an autosomal dominant trait and complete penetrance (4, 5). The FOP gen was discovered in 2006 by Shore et al (6). This disease can lead to complete ossification of the muscular system and was first described in 1648 by Guy Patin as "stone man"(6, 7).…”

Section: Introductionmentioning

confidence: 99%

“…The FOP gen was discovered in 2006 by Shore et al (6). This disease can lead to complete ossification of the muscular system and was first described in 1648 by Guy Patin as "stone man"(6, 7). Trauma to a region of the body may precede the development of a painful inflammatory mass which eventually calcifies.…”

Section: Introductionmentioning

confidence: 99%

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Stone Man: A Case Report

et al. 2012

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Fibrodysplasia ossificans progressiva (FOP) is a rare hereditary connective tissue disease characterized by the progressive ectopic ossification of ligaments, tendons, and facial and skeletal muscles throughout life. Symptoms begin in childhood as localized soft tissue swellings. Immobility and articular dysfunction appear with involvement of the spine and proximal extremities. The temporomandibular joint (TMJ) is a critical component involved in the maxillofacial region, resulting in severe limitation of masticatory function, although TMJ involvement is rare. The aim of this article is to present a 28-year-old man with dental problems and slowly progressive limitation of motion in the jaw, knees, shoulders and hips as well as neck distortion.

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“…The autosomal dominant inheritance of FOP was first described by Sympson in a case report of a seven-year-old boy with classic features of FOP (6, 7). …”

Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Stone Man: A Case Report

et al. 2012

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“…In addition, three novel mutations in NOG published by Semonin et al were subsequently challenged to be technical PCR errors due to the use of a nested PCR approach [28], [36]. Consequently, the necessity to present photographs and radiographs of the studied FOP patients has been emphasized to assure the correct clinical diagnosis and that the same phenotypes are compared [34].…”

Section: Discussionmentioning

confidence: 99%

Functional Analysis of Alleged NOGGIN Mutation G92E Disproves Its Pathogenic Relevance

et al. 2012

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We identified an amino acid change (p.G92E) in the Bone Morphogenetic Protein antagonist NOGGIN in a 22-month-old boy who presented with a unilateral brachydactyly type B phenotype. Brachydactyly type B is a skeletal malformation that has been associated with increased Bone Morphogenetic Protein pathway activation in other patients. Previously, the amino acid change p.G92E in NOGGIN was described as causing fibrodysplasia ossificans progressiva, a rare genetic disorder characterized by limb malformations and progressive heterotopic bone formation in soft tissues that, like Brachydactyly type B, is caused by increased activation of Bone Morphogenetic Protein signaling. To determine whether G92E-NOGGIN shows impaired antagonism that could lead to increased Bone Morphogenetic Protein signaling, we performed functional assays to evaluate inhibition of BMP signaling. Interestingly, wt-NOGGIN shows different inhibition efficacies towards various Bone Morphogenetic Proteins that are known to be essential in limb development. However, comparing the biological activity of G92E-NOGGIN with wt-NOGGIN, we observed that G92E-NOGGIN inhibits activation of bone morphogenetic protein signaling with equal efficiency as wt-NOGGIN, supporting that G92E-NOGGIN does not cause pathological effects. Genetic testing of the child's parents revealed the same amino acid change in the healthy father, further supporting that p.G92E is a neutral amino acid substitution in NOGGIN. We conclude that p.G92E represents a rare polymorphism of the NOGGIN gene - causing neither brachydactyly nor fibrodysplasia ossificans progressiva. This study highlights that a given genetic variation should not be considered pathogenic unless supported by functional analyses.

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“…The question is whether the sequence alterations represent PCR‐induced artifacts or not. In the past, there has already been some debate concerning the presence of NOG mutations in patients with fibrodysplasia ossificans progressiva (2‐4) . Mutations in these patients were identified using a nested PCR reaction, and this increases the likelihood for PCR‐induced artifacts.…”

Section: Comparison Of the Bases At The Different Positions Using Thementioning

confidence: 99%

Acro-Osteolysis and Symphalangism Mutations

Debeer¹

2005

Journal of Bone and Mineral Research

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Reported noggin mutations are PCR errors

Cited by 14 publications

References 3 publications

Stone Man: A Case Report

Stone Man: A Case Report

Functional Analysis of Alleged NOGGIN Mutation G92E Disproves Its Pathogenic Relevance

Acro-Osteolysis and Symphalangism Mutations

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