Recurrence of the D100N mutation in a Chinese family with brachydactyly type A1: Evidence for a mutational hot spot in the Indian hedgehog gene

Zhu, Guiyu; Ke, Xin; Liu, Qiji; Li, Jisheng; Chen, Bingxi; Shao, Changshun; Gong, Yaoqin

doi:10.1002/ajmg.a.31728

Cited by 12 publications

(7 citation statements)

References 14 publications

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“…4,5 Since then, eight mutations have been identified in 13 families. 5,[7][8][9][10][11][12][13][14] Clinical features of patients with mutations in IHH gene are tabulated in ►Table 1. To date, only 13 families (88 affected individuals) with BD have been reported with mutations in IHH gene (►Table 1).…”

Section: Discussionmentioning

confidence: 99%

Severe Form of Brachydactyly Type A1 in a Child with a c.298G > A Mutation in IHH Gene

et al. 2017

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Section: Discussionmentioning

confidence: 99%

Severe Form of Brachydactyly Type A1 in a Child with a c.298G > A Mutation in IHH Gene

et al. 2017

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“…To date, three other BDA1-affected families of Italian, American, and Chinese descent have been found to share this same IHH mutation. 21,23,37 Although it remains possible that the families of Italian and American descent may have originated from this same common founder, the Chinese mutation was found to be flanked by a different haplotype. 37 Another mutation affecting the same codon, c.300C4A, has also been associated with BDA1 in another Chinese family.…”

Section: Mutations In Indian Hedgehog That Causes Brachydactyle A-1mentioning

confidence: 99%

“…Shortening of the first metacarpal, which is typically a distinguishing feature of Brachydactyly type C is a rare but reported finding. 37 Generalized musculoskeletal complaints including arthritis were often reported, as well as the more specific findings of clubfoot and scoliosis. The family described by Raff et al, 12 has not had a mutation reported to date, but the X-rays and clinical photos of the hands clearly show the presence of BDA1.…”

Section: Mutations In Indian Hedgehog That Causes Brachydactyle A-1mentioning

confidence: 99%

Brachydactyly A-1 mutations restricted to the central region of the N-terminal active fragment of Indian Hedgehog

et al. 2009

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Mutations in the gene Indian Hedgehog (IHH) that cause Brachydactyly A-1 (BDA1) have been restricted to a specific region of the N-terminal active fragment of Indian Hedgehog involving codons 95, 100, 131, and 154. We describe two novel mutations in codons 128 and 130, not previously implicated in BDA1. Furthermore, we identified an independent mutation at codon 131 and we also describe a New Zealand family, which carries the 'Farabee' founder mutation and haplotype. All of the BDA1 mutations occur in a restricted area of the N-terminal active fragment of the IHH and are in contrast to those mutations causing an autosomal recessive acrocapitofemoral dysplasia, whose mutations are located at the distal N-and C-terminal regions of IHH-N and are physically separated from the BDA1-causing mutations. The identification of multiple independent mutations in codons 95, 100, and now in 131, implicate a discrete function for this region of the protein. Finally, we present a clinical review of all reported and confirmed cases of BDA1, highlighting features of the disorder, which add to the spectrum of the IHH mutations.

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“…To date, BDA1 has been described as a fully penetrant, autosomal dominant condition. Mutations have been identified in the gene Indian hedgehog (IHH; MIM] 600726) [Byrnes et al, 2009;Gao et al, 2001;Giordano et al, 2003;Kirkpatrick et al, 2003;Liu et al, 2006;McCready et al, 2002McCready et al, , 2005Stattin et al, 2009;Zhu et al, 2007], whose protein product is critical for growth and differentiation of long bone cartilage templates [Vortkamp et al, 1996]. However, mutations in IHH account for approximately 40% of the cases of BDA1.…”

Section: Introductionmentioning

confidence: 99%

Mutations in GDF5 presenting as semidominant brachydactyly A1

et al. 2010

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Brachydactyly A1 (BDA1) is an autosomal dominant disorder characterized by shortness of all middle phalanges of the hands and toes, shortness of the proximal phalanges of the first digit, and short stature. Missense mutations in the Indian Hedgehog gene (IHH) are known to cause BDA1, and a second locus has been mapped to chromosome 5p. In a consanguineous French Canadian kindred with BDA1, both IHH and the 5p locus were excluded. Microsatellites flanking GDF5 on chromosome 20q were found to cosegregate with the disease. Sequencing of the GDF5 coding region revealed that a mildly affected individual in the family was heterozygous, and that all of the severely affected individuals were homozygous for a novel missense c.1195C>T mutation that predicts a p.Arg399Cys substitution at a highly conserved amino acid. Functional analysis demonstrated that although the p.Arg399Cys mutant is able to stimulate chondrogenesis, it is much less effective than wild-type GDF5. This data confirms genetic heterogeneity in BDA1, demonstrates that mutations upstream of IHH can result in BDA1, and shows that BDA1 can result from semidominant mutations in GDF5.

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Recurrence of the D100N mutation in a Chinese family with brachydactyly type A1: Evidence for a mutational hot spot in the Indian hedgehog gene

Cited by 12 publications

References 14 publications

Severe Form of Brachydactyly Type A1 in a Child with a c.298G > A Mutation in IHH Gene

Severe Form of Brachydactyly Type A1 in a Child with a c.298G > A Mutation in IHH Gene

Brachydactyly A-1 mutations restricted to the central region of the N-terminal active fragment of Indian Hedgehog

Mutations in GDF5 presenting as semidominant brachydactyly A1

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