MECP2 duplication syndrome in a patient from Cameroon

MECP2 duplication syndrome (MDS; OMIM 300260) is an X‐linked neurodevelopmental disorder caused by nonrecurrent duplications of the Xq28 region involving the gene methyl‐CpG‐binding protein 2 (MECP2; OMIM 300005). The core phenotype of affected individuals includes infantile hypotonia, severe intellectual disability, very poor‐to‐absent speech, progressive spasticity, seizures, and recurrent infections. The condition is 100% penetrant in males, with observed variability in phenotypic expression within and between families. Features of MDS in individuals of African descent are not well known. Here, we describe a male patient from Cameroon, with MDS caused by an inherited 610 kb microduplication of Xq28 encompassing the genes MECP2, IRAK1, L1CAM, and SLC6A8. This report supplements the public data on MDS and contributes by highlighting the phenotype of this condition in affected individuals of African descent.     

A mutation analysis of the<Emphasis Type="Italic"> BRCA1</Emphasis> gene in 140 families from southeast France with a history of breast and/or ovarian cancer

A mutation analysis of the BRCA1 gene in 140 French families with a history of breast cancer or breast-ovarian cancer revealed several deleterious germline mutations, as well as rare sequence variants. The 19 genetics variants were of 15 different types, two of which had not been reported in the Breast cancer Information Core (BIC) database. Five distinct truncating mutations, leading to putative nonfunctional proteins, were identified out of 140 index cases (3.5%). One novel nonsense mutation, C4491T, was reported, whereas the four other BRCA1 deleterious mutations identified consisted of frequent frameshifts in the nucleotide sequence. One splice variant (331+3A>G) and thirteen missense variations leading to amino acid substitutions of unknown structural and functional importance were identified. Among these, two BRCA1 missense mutations, A120G and T243C could be considered as suspected deleterious. The first missense mutation modified the initiation codon (M1V) and the second (C39R) may have consequences on the structure and functioning of the BRCA1 protein by modifying cysteine ligands from the RING finger domain. As expected BRCA1 gene alteration, including missense mutations of unknown biological significance, were more frequent in families with a history of breast-ovarian-cancer (32%) than in breast-cancer-only families (12%).     

New HLA-A*11 allele,A*1112, identified by sequence-based typing

In this report, we describe the identification of HLA-A*1112, a novel HLA-A*11 allele found in two Italian families. The new allele was detected during routine HLA typing by a polymerase chain reaction sequence-specific primer and was confirmed by high-resolution sequencing-based typing. The nucleotide sequences of HLA-A*1112 exons 2 and 3 are identical to HLA-A*11011 except for a single nucleotide substitution in codon 90 (GAC-->GCC).     

Molecular aspects of a novel HLA-A*02 allele (A*0297): the first HLA class I allele mutated at codon 232

We describe a new HLA-A*02 allele, identified in a cord blood unit and in her mother. Nucleotide sequence analysis showed the presence of a new HLA-A*02 allele identical to HLA-A*02010101 except for a non-synonymous nucleotide exchange in exon 4 modifying codon 232 from GAG (Glu) to GAC (Asp). No other human leucocyte antigen class I allele sequenced so far shows this triplet at codon 232. The amino acid exchange affects a position that is part of the membrane proximal domain of class I major histocompatibility complex (MHC), designated alpha 3, and involved in the interaction with CD8 molecule. Using molecular modelling approach, the interactions between different subunits of the native and mutated forms of MHC-I resulted in relevant changes.     

Outcomes of Long Tapered Hydroxyapatite-Coated Stems in Revision Total Hip Arthroplasty

The purpose of this study was to evaluate the outcome of femoral component revisions using a long tapered HA coated femoral revision stem. Between 2001 and 2008, 55 femoral component revisions were performed using this stem. Forty-one patients were available for follow up evaluation at average of 59 months. The clinical results were evaluated using the HHS and serial radiographs were evaluated for loosening. The mean HHS was 71 (range 22–100). Three hips required revision of KAR stem (1 aseptic loosening, 1 infection, 1 limb length discrepancy). Only one prosthesis demonstrated radiographic evidence of subsidence. Our study suggests that long tapered HA coated revision femoral components can provide stable fixation and in-growth in cases where there is good proximal femoral bone stock and favorable canal geometry.     

Surgery for carcinoma of the gallbladder. Our experience

BACKGROUND: Carcinoma of the gallbladder is a gastrointestinal malignancy with a very poor prognosis. The 5-year survival rate amounts to less than 5% in most series. In this study we reviewed the results of surgical treatment for gallbladder carcinoma with special reference to extended radical procedures. METHODS: Between 1995 and 2000 we enrolled 36 patients (17 males and 19 females), 24 of whom were treated with simple cholecystectomy and 12 with radical resection (partial hepatectomy, regional lymphadenectomy, and common bile duct resection). The tumours were classified by stage using the criteria of the American Joint Committee on Cancer (AJCC). Stages, operative procedures, results of pathologic examinations and the outcome of the resected cases were reviewed. RESULTS: There were 2 postoperative deaths (0.55%). The mean follow-up period was 19.1 months (range 1-60). For stage I and II disease extended cholecystectomy had a better result than simple cholecystectomy: the 5-year survival rates were 38.4 versus 19%, respectively. For the patients with advanced stage III or IV gallbladder carcinoma, a significant advantage of survival resulted in case of liver resection as compared to surgical treatment without liver resection: the 5-year survival rates were 20 and 0%, respectively. CONCLUSIONS: The survival of stage I-II patients was good. For the patients in higher stages the prognosis was significantly worse. In these cases more aggressive surgery may be needed.     

Early failure of precoated femoral components in primary total hip arthroplasty

BACKGROUND: In an effort to decrease the rate of aseptic loosening, certain cemented femoral components were designed to have a roughened or textured surface with a methylmethacrylate precoating. Reports differ as to whether this step has increased or decreased the rate of failure. This study was designed to evaluate this issue. METHODS: Five hundred and fourteen hips treated with a cemented Harris Precoat stem (Zimmer, Warsaw, Indiana) were evaluated clinically and radiographically and compared with 254 hips treated with an uncoated Harris Design-2 stem (Howmedica, East Rutherford, New Jersey). Prostheses that had been removed at revision were examined. The cementing and surgical techniques were identical and the population demographics were similar for these two groups. RESULTS: The mean durations of follow-up were 8.4 and 13.5 years for the Precoat and uncoated Design-2 stems, respectively. At those times, at least forty-nine (9.5%) of the 514 Precoat components and at least ten (3.9%) of the 254 uncoated Design-2 stems had failed (p = 0.006). Five Precoat stems fractured, and no uncoated Design-2 stems fractured. Component failure was associated with use in young, active, heavy men with a diagnosis of avascular necrosis and generally with the use of smaller components. The cementing technique was satisfactory in the majority of the patients, and there were no qualitative differences in cementing technique between the hips that failed and those that did not. The mechanisms of failure of the Precoat prostheses included bone-cement loosening, focal osteolysis, stem fracture, and prosthesis-cement debonding. Fractures of smaller components occurred as a result of fatigue failure and were associated with good distal fixation but proximal stem loosening. CONCLUSIONS: The rate of failure of roughened, precoated, cemented femoral components was considerably higher and occurred earlier than that of femoral components that were neither textured nor precoated with methylmethacrylate. Younger patients with avascular necrosis had a higher risk of failure; however, this factor alone did not completely explain the differences in outcome between these two components. The causes of aseptic loosening are multifactorial and may be related to component design and size as well as to precoating and surface finish.     

现代氧化铝陶瓷应用于全髋关节置换术的可靠性

全髋关节置换术中,陶瓷部件失效是一种十分罕见而严重的并发症.随着陶瓷材料质量、制作工艺及假体设计方面的改进,陶瓷部件失效的发生率正稳定地下降.自2000年1月至2006年5月,Ceram Tec公司生产的BIOLOX品牌陶瓷部件失效的发生率约为0.02%,即一万例中有2例发生.目前全髋关节置换术中陶瓷部件发生失效的风险估计为万分之二,其中大多发生于陶瓷球头.因此,氧化铝陶瓷在现代全髋关节置换术中的应用安全可靠,且具有极低的失效风险.