Identification of CANT1 Mutations in Desbuquois Dysplasia

Huber, Céline; Oulès, Bénédicte; Bértoli, Marta; Chami, Mounia; Fradin, Mélanie; Alanay, Yasemin; Al‐Gazali, Lihadh; Ausems, Margreet G. E. M.; Bitoun, Pierre; Cavalcanti, Denise Pontes; Krebs, Alexander; Merrer, Martine Le; Mortier, Geert; Shafeghati, Yousef; Superti‐Furga, Andrea; Robertson, Stephen P.; Goff, Carine Le; Muda, Andrea Onetti; Paterlini‐Bréchot, Patrizia; Münnich, Arnold; Cormier‐Daire, Valérie

doi:10.1016/j.ajhg.2009.10.001

Cited by 91 publications

(126 citation statements)

References 15 publications

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“…Recently, Huber et al 4 identified mutations in the gene encoding the calcium-activated nucleotidase 1 (CANT1) in DBQD type 1, which is followed by Faden et al 5 We also found CANT1 mutations in DBQD type 2 and Kim variant. In our series, we identified CANT1 mutations in all seven patients from five unrelated families with DBQD Kim variant, and all patients had c.676G4A (p.V226M).…”

Section: Introductionmentioning

confidence: 60%

A founder mutation of CANT1 common in Korean and Japanese Desbuquois dysplasia

et al. 2011

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Desbuquois dysplasia (DBQD) is a severe skeletal dysplasia of autosomal recessive inheritance. DBQD is classified into types 1 and 2 based on presence or absence of hand anomalies. In a previous study, we found a CANT1 (for calcium-activated nucleotidase 1) mutation, c.676G4A in five DBQD families. They were all East Asians (Japanese or Korean). The high prevalence of the same mutation among Japanese and Korean suggested that it is a common founder mutation in the two populations. To examine a possible common founder, we examined the region around CANT1 in chromosomes with c.676G4A mutation by genotyping polymorphic markers in the region for the families. We examined their haplotypes using the family data. We identified in all families a common haplotype containing the CANT1 mutation that ranged up to 550 kb. The two unrelated carriers of the mutation in general populations in Korea and Japan could also have the haplotype. We estimated the age of the founder mutation as B1420 years (95% CI¼880-1940 years). The c.676G4A mutation of CANT1 commonly seen in Japanese and Korean DBQD should be derived from a common founder.

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Section: Introductionmentioning

confidence: 60%

A founder mutation of CANT1 common in Korean and Japanese Desbuquois dysplasia

et al. 2011

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“…Early (perinatal) lethality in four of these patients was associated with nonsense mutations. 12 Very recently, mutations in the CANT1 gene have also been found associated with the DBQD type 2, as well as with the so called 'Kim variant' of DBQD. 13 …”

Section: Introductionmentioning

confidence: 99%

Desbuquois dysplasia type I and fetal hydrops due to novel mutations in the CANT1 gene

et al. 2011

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We report on three hydropic fetuses of 17, 22 and 25 gestational weeks from three distinct families presenting with Desbuquois dysplasia type 1. All fetuses showed brachymelia and characteristic dysmorphic features. X-ray studies revealed d-shaped extraphalangeal bones and disease-specific prominence of the lesser trochanter, varying in severity with fetal age. Early lethal manifestation of the disorder was reflected in lung hypoplasia and in early death of similarly affected siblings in cases 1 and 2. All families were German Caucasians by descent. Sequence analysis of the CANT1 gene revealed two frameshift mutations, c.228_229insC and c.277_278delCT, in homozygous and compound heterozygous configuration, respectively, and a homozygously novel missense mutation, c.336C4A (p.D112E), located within a highly conserved region of exon 2. Haplotype analyses by high-resolution single-nucleotide polymorphism array showed that the haplotype associated with c.228_229insC may be traced to a single founder in the German population.

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“…Calciumactivated nucleotidase 1 gene mutations have been identified in nine families with Desbuquois type 1, a gene that hydrolyses UDP followed by guanosine diphosphate and UTP [466].…”

Section: Desbuquois Dysplasiamentioning

confidence: 99%

Purinergic signalling in the musculoskeletal system

Burnstock

Arnett

Orriss

2013

Purinergic Signalling

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It is now widely recognised that extracellular nucleotides, signalling via purinergic receptors, participate in numerous biological processes in most tissues. It has become evident that extracellular nucleotides have significant regulatory effects in the musculoskeletal system. In early development, ATP released from motor nerves along with acetylcholine acts as a cotransmitter in neuromuscular transmission; in mature animals, ATP functions as a neuromodulator. Purinergic receptors expressed by skeletal muscle and satellite cells play important pathophysiological roles in their development or repair. In many cell types, expression of purinergic receptors is often dependent on differentiation. For example, sequential expression of P2X5, P2Y 1 and P2X2 receptors occurs during muscle regeneration in the mdx model of muscular dystrophy. In bone and cartilage cells, the functional effects of purinergic signalling appear to be largely negative. ATP stimulates the formation and activation of osteoclasts, the bone-destroying cells. Another role appears to be as a potent local inhibitor of mineralisation. In osteoblasts, the bone-forming cells, ATP acts via P2 receptors to limit bone mineralisation by inhibiting alkaline phosphatase expression and activity. Extracellular ATP additionally exerts significant effects on mineralisation via its hydrolysis product, pyrophosphate. Evidence now suggests that purinergic signalling is potentially important in several bone and joint disorders including osteoporosis, rheumatoid arthritis and cancers. Strategies for future musculoskeletal therapies might involve modulation of purinergic receptor function or of the ecto-nucleotidases responsible for ATP breakdown or ATP transport inhibitors.

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Identification of CANT1 Mutations in Desbuquois Dysplasia

Cited by 91 publications

References 15 publications

A founder mutation of CANT1 common in Korean and Japanese Desbuquois dysplasia

A founder mutation of CANT1 common in Korean and Japanese Desbuquois dysplasia

Desbuquois dysplasia type I and fetal hydrops due to novel mutations in the CANT1 gene

Purinergic signalling in the musculoskeletal system

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