A type II collagen mutation also results in oto-spondylo-megaepiphyseal dysplasia

Miyamoto, Yasuo; Nakashima, Eiji; Hiraoka, Hisatada; Ohashi, Hirofumi; Ikegawa, Shiro

doi:10.1007/s00439-005-0058-0

Cited by 19 publications

(10 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This latter variant was previously reported in an oto-spondylo-megaepiphyseal dyplasia case (OSMED, #215150) and was shown to cause exon skipping, resulting in short transcripts that escaped NMD and led to an in-frame deletion of the triple helical region of the collagen chain. 24 Our observations provide a nearly 15% increase in the number of novel variants shown in previous records and illustrate the wide mutability of the COL2A1 gene and its various associated phenotypes. 25 Our results also demonstrate the limits of focusing on a single gene during genetic diagnosis given the lack of clear phenotype to genotype correlations.…”

Section: Discussionsupporting

confidence: 64%

See 1 more Smart Citation

The expanding spectrum of COL2A1 gene variants IN 136 patients with a skeletal dysplasia phenotype

Barat‐Houari

Dumont²,

Fabre³

et al. 2015

Eur J Hum Genet

View full text Add to dashboard Cite

Heterozygous COL2A1 variants cause a wide spectrum of skeletal dysplasia termed type II collagenopathies. We assessed the impact of this gene in our French series. A decision tree was applied to select 136 probands (71 Stickler cases, 21 Spondyloepiphyseal dysplasia congenita cases, 11 Kniest dysplasia cases, and 34 other dysplasia cases) before molecular diagnosis by Sanger sequencing. We identified 66 different variants among the 71 positive patients. Among those patients, 18 belonged to multiplex families and 53 were sporadic. Most variants (38/44, 86%) were located in the triple helical domain of the collagen chain and glycine substitutions were mainly observed in severe phenotypes, whereas arginine to cysteine changes were more often encountered in moderate phenotypes. This series of skeletal dysplasia is one of the largest reported so far, adding 44 novel variants (15%) to published data. We have confirmed that about half of our Stickler patients (46%) carried a COL2A1 variant, and that the molecular spectrum was different across the phenotypes. To further address the question of genotype-phenotype correlation, we plan to screen our patients for other candidate genes using a targeted next-generation sequencing approach.

show abstract

Section: Discussionsupporting

confidence: 64%

“…To address this issue, we are now implementing next-generation sequencing approaches in our routine settings. 24 …”

Section: Discussionmentioning

confidence: 99%

The expanding spectrum of COL2A1 gene variants IN 136 patients with a skeletal dysplasia phenotype

Barat‐Houari

Dumont²,

Fabre³

et al. 2015

Eur J Hum Genet

View full text Add to dashboard Cite

show abstract

“…It is tempting to assume that weak joint cartilage and abnormal subchondral trabeculae as a result of COL2A1 mutations are vulnerable to subchondral stress fracture of the femoral head, resulting in LCPD. COL2A1 mutations, or type II collagenopathies, cause several types of skeletal dysplasias that primarily aVect capital femoral epiphyses in growing children, such as spondyloepiphyseal dysplasia congenita (OMIM 183900), Kniest dysplasia (OMIM 156550), Stickler dysplasia (OMIM 108300), oto-spondylo-megaepiphyseal dysplasia (OMIM 215150;Miyamoto et al 2005) and spondyloepiphyseal dysplasia with premature onset arthrosis (OMIM 208230). The epiphyseal dysplasias in these disorders are basically congenital, symmetrical and progressive.…”

Section: Discussionmentioning

confidence: 99%

A recurrent mutation in type II collagen gene causes Legg-Calvé-Perthes disease in a Japanese family

et al. 2007

Self Cite

View full text Add to dashboard Cite

Legg-Calvé-Perthes disease (LCPD) is a common childhood hip disorder characterized by sequential stages of involvement of the capital femoral epiphyses, including subchondral fracture, fragmentation, re-ossification and healing with residual deformity. Most cases are sporadic, but familial cases have been described, with some families having multiple affected members. Genetic factors have been implicated in the etiology of LCPD, but the causal gene has not been identified. We have located a missense mutation (p.G1170S) in the type II collagen gene (COL2A1) in a Japanese family with an autosomal dominant hip disorder manifesting as LCPD and showing considerable intra-familial phenotypic variation. This is the first report of a mutation in hereditary LCPD. COL2A1 mutations may be more common in LCPD patients than currently thought, particularly in familial and/or bilateral cases.

show abstract

“…Otospondylomegaepiphyseal dysplasia (OSMED) is a skeletal disorder, associated with severe sensorineural hearing loss, enlarged epiphysis and the early onset of osteoarthritis. Miyamoto et al (17) identified a COL2A1 mutation at a splice-acceptor site within intron 10 in an OSMED patient. Liu et al identified three families in which there was autosomal dominant inheritance of the avascular necrosis of the femoral head (ANFH), and mapped the chromosomal position of the gene to 12q13.…”

Section: Discussionmentioning

confidence: 99%

A genetic pedigree analysis to identify gene mutations involved in femoral head necrosis

Wang

Pan

Zhu

2014

Molecular Medicine Reports

View full text Add to dashboard Cite

The present study presents results from a linkage and mutation screening analysis aiming to identify the causative gene of femoral head necrosis, also known as osteonecrosis of femoral head (ONFH), in a Chinese pedigree. We collected clinical data on the osteonecrosis pedigree, and extracted blood and genomic DNA from the family members. Polymerase chain reaction (PCR) and direct sequencing allowed to identify a mutation in the COL2A1 gene of the proband; the clinical manifestations of the proband meet the criteria for osteonecrosis. The exons of COL2A1 were amplified by polymerase chain reaction and mutation screening was conducted by direct sequencing in all the family members. The locus was also sequenced in 50 unrelated healthy controls. The c.3665G>A heterozygous mutation was detected in patients of the pedigree, but not in healthy individuals. We conclude that a mutation in the COL2A1 gene is the causative agent of ONFH in this family. Therefore, this mutation may be associated with osteonecrosis in Chinese populations.

show abstract

A type II collagen mutation also results in oto-spondylo-megaepiphyseal dysplasia

Cited by 19 publications

References 14 publications

The expanding spectrum of COL2A1 gene variants IN 136 patients with a skeletal dysplasia phenotype

The expanding spectrum of COL2A1 gene variants IN 136 patients with a skeletal dysplasia phenotype

A recurrent mutation in type II collagen gene causes Legg-Calvé-Perthes disease in a Japanese family

A genetic pedigree analysis to identify gene mutations involved in femoral head necrosis

Contact Info

Product

Resources

About