Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Alternative splicing of exon 14 determines nuclear or cytoplasmic localisation of fmr1 protein isoforms

Impaired expression of the FMR1 gene is responsible for the fragile X mental retardation syndrome. The FMR1 gene encodes a cytoplasmic protein with RNA-binding properties. Its complex alternative splicing leads to several isoforms, whose abundance and specific functions in the cell are not known. We have cloned in expression vectors, cDNAs corresponding to several isoforms. Western blot comparison of the pattern of endogenous FMR1 proteins with these transfected isoforms allowed the tentative identification of the major endogenous isoform as ISO 7 and of a minor band as an isoform lacking exon 14 sequences (ISO 6 or ISO 12), while some other isoforms (ISO 4, ISO 5) were not expressed at detectable levels. Surprisingly, in immunofluorescence studies, the transfected splice variants that exclude exon 14 sequences (and have alternate C-terminal regions) were shown to be nuclear. Such differential localisation was however not seen in subcellular fractionation studies. Analysis of various deletion mutants suggests the presence of a cytoplasmic retention domain encoded in exon 14 and of a nuclear association domain encoded within the first eight exons that appear however to lack a typical nuclear localisation signal.      

Novel TAP1 polymorphisms in indigenous Zimbabweans: their potential implications on TAP function and in human diseases

Because of the essential role of transporter associated with antigen processing (TAP1 or TAP2) molecule in antigen processing, the implication of its polymorphism as a factor involved in human diseases and the possible genetic variation at this locus among ethnically diverse populations, we underwent a study to analyze the full extent of TAP1 polymorphism in an indigenous Zimbabwean population (Shona ethnic group). Using single-stranded conformation polymorphism and DNA direct sequencing procedures, we detected the presence of 11 nucleotide sequence variations in the entire coding region of TAP1. Of these variants, eight are nonconservative substitutions with respect to amino acid composition and are located in a critical part of the protein that could modulate its function. Five new polymorphic sites were identified in exon 1 (codons 7 Pro --> Ser, 17 Gly --> Arg, 141 Val --> Val), exon 6 (codon 419 Gly --> Cys), and exon 7 (codon 487 Arg --> Arg). Significant differences were seen in the distribution of TAP1*0201 and TAP1*0401 alleles, and codon 333 (Ile --> Val) polymorphism among African and non-African populations. Thus, TAP1 polymorphism has evolved differently among populations presumably because of the evolutionary pressures generated by prevalent pathogens in these geographically distinct regions.     

Immediate repair of urethroperineal fistulas after abdominoperineal amputation by means of a cutaneo-muscular flap of the gluteus maximus. Apropos of 2 successfully treated cases

Although a rare complication, the development of a urethro-perineal urinary fistula immediately after abdomino-perineal amputation is a difficult problem to solve. The fragility of the membranous urethra immediately in contact with the exenterated pelvic cavity which takes several weeks to fill in makes any attempt at isolated direct suture very hazardous. Secondary repair is also frequently difficult and the "functional prognosis is far from being always favourable". The major handicap resulting from the perpetuation of this type of fistula has led us to propose an attempt at immediate repair as soon as it is diagnosed with filling of the pelvi-perineal cavity by a cutaneo-muscular flap taken from gluteus maximus. In the two cases in which this treatment was performed, the fistula was cured and a good quality functional result was obtained.     

Needle biopsy of renal allografts: comparison of two techniques

Two techniques for renal allograft biopsy were retrospectively evaluated to compare relative safety and efficacy. After ultrasound (US) localization of the kidney and biopsy with a hand-held 14-gauge cutting needle, an adequate specimen was obtained in 74 of 77 cases (96%). Major complications occurred in six of these 77 cases (8%). One hundred four biopsies were performed by using a smaller 18-gauge cutting needle with a spring-loaded biopsy "gun" and real-time US guidance. With this newer technique, specimens adequate for diagnosis were obtained in 99 biopsies (95%). There was a single major complication with this technique (1%). The 18-gauge needle with real-time US guidance yields comparably adequate specimens with a lower frequency of complications.     

胰腺多房性潴留性囊肿1例

0　引言　胰腺多房性潴留性囊肿极为罕见,我科收治1例,报道如下.1　病例报告　患者,男,29岁,因发现右上腹包块11d入院,缘于11d前无明显诱因感右上腹痛,仅局限于右上腹部,无肩背部放散痛,伴间歇性发热,体温最高达38.3℃,经抗炎,对症治疗无效.并逐渐可触及右上腹有一肿块,在当地医院行穿刺检查为脓血性液体.镜检发现炎性细胞,B超示:胆囊窝下方及右肾内侧及腹腔动脉,下腔静脉外前方可见异常区,大小约9.1cm×6.6cm×7.6cm,边界清楚,形态不规则,内呈蜂窝状,可见多个大小不等的液性暗区,CT示:右上腹部上腔静脉前方6.0cm×9.0cm肿块和周围组织粘…     

玻璃体切除术治疗外伤性眼内炎62例

0　引言　外伤性眼内炎是眼外伤的常见并发症 ,对视力及眼球威协极大 .由于病原体随致伤物直接进入眼内 ,在眼内和玻璃体繁殖 ,产生剧烈炎症反应 ,对眼内组织造成严重破坏 .如不及时而有效的控制 ,终使视力丧失 ,眼球萎缩 .近年随着现代玻璃体手术的发展 ,外伤性眼内炎的治愈率明显提高 .现将我科收治的 6 2例报告如下 .1　对象和方法1 .1　对象 1 996 - 0 6 / 1 998- 0 6我院连续收治 6 2例外伤性眼内炎 ,其中男 5 0例 ,女 1 2例 ,年龄 2～ 45岁 ,平均 1 6 .5岁 .1 4岁以下儿童 38例 ,占 6 1 .3% .以致伤原因分类 :角膜穿通伤30例 ,巩膜穿…     

IMPACTED RIGHT UPPER CENTRAL INCISOR AND TRANSPOSITION OF TWO OTHER ANTERIOR TEETH ON THE SAME SIDE (A Case Report)

A young boy presented with an uncommon finding of impaction of upper right central incisor and transposition of canine and lateral incisor on the same side. Esthetic management of his cosmetic problem which included fixed appliance therapy followed by light cure restorations is discussed.KEY WORDS: Impaction, Transposition