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

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.676G>A 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.676G>A 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 ∼ 1420 years (95% CI=880-1940 years). The c.676G>A mutation of CANT1 commonly seen in Japanese and Korean DBQD should be derived from a common founder.

CANT1 mutation is also responsible for Desbuquois dysplasia, type 2 and Kim variant.

BACKGROUND: Desbuquois dysplasia (DD) is a recessively inherited condition characterised by short stature, generalised skeletal dysplasia and advanced bone maturation. DD is both clinically and radiographically heterogeneous, and two subtypes have been distinguished based on the presence (type 1) or absence (type 2) of an accessory metacarpal bone. In addition, an apparently distinct variant without additional metacarpal bone but with short metacarpals and long phalanges (Kim variant) has been described recently. Mutations in the gene that encodes for CANT1 (calcium-activated nucleotidase 1) have been identified in a subset of patients with DD type 1. METHODS: A series of 11 subjects with DD from eight families (one type 1, two type 2, five Kim variant) were examined for CANT1 mutations by direct sequencing of all coding exons and their flanking introns. RESULTS: Eight distinct mutations were identified in seven families (one type 1, one type 2 and all 5 Kim variant): three were nonsense and five were missense. All missense mutations occurred at highly conserved amino acids in the nucleotidase conserved regions of CANT1. Measurement of nucleotidase activity in vitro showed that the missense mutations were all associated with loss-of-function. CONCLUSION: The clinical-radiographic spectrum produced by CANT1 mutations must be extended to include DD type 2 and Kim variant. While presence or absence of an additional metacarpal ossification centre has been used to distinguish subtypes of DD, this sign is not a distinctive criterion to predict the molecular basis in DD.

Poor results of the cementless total hip arthroplasty with a nonporous coated acetabular component: AcSys Shearer Cup.

BACKGROUND: This study followed patients for a minimum of 7 years after primary total hip arthroplasty using cementless acetabular components and evaluated their outcomes. METHODS: We followed 73 patients (75 hips), who had undergone total hip arthroplasty with cementless nonporous coated acetabular components (3M AcSys Shearer Cup) for a mean of 9.8 years (range 7-13 years). There were 61 women and 12 men with a mean age of 53 years (range 27-69 years) at surgery. The diagnosis was primary osteoarthritis in 9 hips, osteoarthritis secondary to developmental dysplasia in 58 hips, osteonecrosis of the femoral head in 6 hips, and rheumatoid arthritis in 2 hips. RESULTS: Three cups were revised because of aseptic loosening, and one cup was revised following removal of the prosthesis due to deep infection. Radiographic loosening was observed in 22 hips at the latest follow-up. The survival rate at 10 years was 94.7% with revision as the endpoint and 72% with radiographic loosening as the endpoint. The Merle d'Aubigné and Postel hip score showed significant improvement postoperatively and was maintained well even in cases showing radiographic loosening. CONCLUSIONS: The intermediate radiological results with the AcSys Shearer Cup were unsatisfactory because of the high loosening rate, although the revision rate was low. The nonporous outer surface and the poor fixation mechanism between the metal shell and liner may have contributed to the high failure rate. Regular radiological review is recommended when this cup is used because early loosening is often painless.

A novel filamentous phage, fs-2, of Vibrio cholerae O139.

A novel filamentous bacteriophage, fs-2, was isolated from Vibrio cholerae O139 strain MDO14. The fs-2 phage was a long filamentous particle 1200 nm long and 7 nm wide. The purified phage formed a turbid plaque when spotted on a lawn of the host organisms. The plaque-formation activity was stable following heating to 70 degrees C but was inhibited by treatment with chloroform. fs-2 had a single-stranded DNA genome and was converted to a double-stranded replicative form in the host cell. Almost all V. cholerae O139 and O1 El Tor biotype strains tested were sensitive to the phage, but most O1 classical strains and non-O1 non-O139 strains were resistant. The fs-2 genome comprised 8651 nucleotides containing nine open reading frames, five of which had predicted protein products partially homologous to the reported protein products of other filamentous phages. Although the extent of the homology was not particularly high, the genetic organization of other filamentous phages appears to be preserved in fs-2. The phage was not integrated into the chromosome of its host, but a 715 nucleotide fragment located in the large intergenic region of fs-2 was highly homologous to a part of region RS2 (repetitive sequence 2) of the V. cholerae CTX phi sequence which is speculated to be required for integration of the phage into the V. cholerae chromosome at a specific site.