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Biomedical subjects

M Broyer

Publications and source records attributed to M Broyer.

At least 91 records · Page 5Linked to original sources
PubMed1996

Spectrum of mutations in the COL4A5 collagen gene in X-linked Alport syndrome.

Alport syndrome is a mainly X-linked hereditary disease of basement membranes that is characterized by progressive renal failure, deafness, and ocular lesions. It is associated with mutations of the COL4A5 gene located at Xq22 and encoding the alpha5 chain of type IV collagen. We have screened 48 of the 51 exons of the COL4A5 gene by SSCP analysis and have identified 64 mutations and 10 sequence variants among 131 unrelated Alport syndrome patients. This represents a mutation-detection rate of 50%. There were no hot-spot mutations and no recurrent mutations in our population. The identified mutations were 6 nonsense mutations, 12 frameshift mutations, 17 splice-site mutations, and 29 missense mutations, 27 of the latter being glycine substitutions in the collagenous domain. Two of these occurred on the same allele in one patient and segregated with the disease in the family. We showed that some of the glycine substitutions could be associated with the lack of immunological expression of the alpha3(IV)-alpha5(IV) collagen chains in the glomerular basement membrane.

Adolescent↗
PubMed1996

[Value of cyclosporine in the treatment of the recurrence of nephrosis after renal transplantation].

From May 1992 to December 1994, 14 children with end stage renal failure secondary to steroid-resistant idiopathic nephrotic syndrome received a cadaver kidney graft. Immediate recurrence of the nephrotic syndrome occurred in four patients. In the four patients, a complete remission was observed shortly after the start of intravenous cyclosporin; two children received in addition methylprednisolone pulses for secondary rejection. Two children were still protein-free 9 and 15 months after transplantation. In the third patient, proteinuria relapsed after 9 months of complete remission and persisted in spite of the reintroduction of intravenous cyclosporin. The fourth graft was lost at 3.5 month from irreversible rejection. The creatinine clearance of the 3 functioning grafts was respectively: 73, 76 and 92 ml/mn/1.73 m2 16, 10 and 15 months after transplantation. Intravenous cyclosporin started shortly after the recurrence, maintaining blood levels between 200 and 300 ng/ml, may induce a remission in recurrent nephrotic syndrome after renal transplantation in childhood.

Child, Preschool↗
PubMed1995

A 11 Mb YAC-based contig spanning the familial juvenile nephronophthisis region (NPH1) located on chromosome 2q.

A gene (NPH1) responsible for approximately 90% of the purely renal form of familial juvenile nephronophthisis, a progressive tubulo-interstitial kidney disorder, maps to human chromosome 2. We report the construction of a YAC-based contig spanning the critical NPH1 region and the flanking genetic markers. This physical map was integrated with a refined genetic map that restricted the NPH1 interval to about 2 cM; this interval corresponds to a maximum physical distance of 3.5 Mb. The entire contig covers 9 cM between the loci D2S135 and D2S121. The maximum physical distance between these two markers is approximately 11.3 Mb. Forty-five sequence-tagged sites, including six genes, have been located within this contig. PAX8, a member of the human paired box gene family, that is expressed in the developing kidney, was assigned outside the restricted NPH1 critical region and cannot therefore be regarded as a candidate gene. This set of overlapping clones represents a useful resource for further targeted development of genetic markers and for the characterization of candidate genes responsible for juvenile nephronophthisis.

Base Sequence↗
PubMed1995

Craniosynostosis and kidney malformation in a case of Hennekam syndrome.

Hennekam syndrome is a rare autosomal recessive syndrome which was described for the first time in 1989. Here, we present a girl with intestinal lymphangiectasia, severe lymphedema of limbs, seizures, mild mental retardation, and facial anomalies consistent with the diagnosis of Hennekam syndrome. In addition, she had an ectopic kidney and craniosynostosis of the coronal suture, 2 manifestations not previously reported in this syndrome. While the molecular basis of Hennekam syndrome remains, as yet, unknown, this report illustrates its variable clinical expression.

Craniosynostoses↗
PubMed1995

[Bacterial complications of nephrotic syndrome in children].

OBJECTIVES: Evaluate bacterial infection epidemiology and pathophysiology in children with nephrotic syndrome. METHODS: From January 1983 to December 1992, 399 children with the nephrotic syndrome were admitted in 3 University Pediatric wards (Paris Enfants Malades, Lyon Edouard Herriot, Lyon Debrousse). Severe bacterial infection was diagnosed when the patient's condition has justified an intravenous antibiotherapy. RESULTS: Forty-eight bacterial infections were noted in 32 patients (8%); the infection was the first symptom of the disease in 10 patients (31%); one patient died shortly after admission. Severe bacterial infection concerned steroid-resistant nephrotic syndrome in 13 cases (41%), but only 7 out of them received immunosuppressive agents at the time of the infection. Eleven children (34%) experienced recurrent infections (1 to 6 recurrences), several of which under antibioprophylaxy. Half of the infections involved peritonitis and 50% of the identified germs were S. pneumoniae. However, peritonitis was not always related to S. pneumoniae (1 H. influenzae among 9 identified germs). CONCLUSIONS: These data demonstrate the importance of microbiological sampling and justify a first-line antibiotherapy using a third generation cephalosporin. The presentation of severe bacterial infections show that it is less a iatrogenic event than a consequence of immunological disturbances induced by the nephrotic syndrome itself, as suggested by the acquired deficiency of factor I and B. Despite recent advances in antibiotic strategies responsible for a significant reduction in the severity of such infections (1 death among 32 patients), preventive treatments are quite disappointing.

Adolescent↗
PubMed1995

Haemolytic uraemic syndrome: prognostic factors in children over 3 years of age.

Previous studies have shown that age at onset of primary haemolytic uraemic syndrome (HUS) is a feature of prognostic significance, the disease being of much better outcome in paediatric patients younger than 3 years than in older children. In an attempt to find an explanation for such a difference, we analysed the clinical and pathological features of 42 children over 3 years of age who presented with HUS between 1955 and 1990 in our department. On the basis of the presence of a prodromal diarrhoea, we divided our patients into two groups: 21 children presented with the diarrhoea-associated (typical or D+) form of HUS, whereas 21 had the non-diarrhoea-associated (atypical or D-) form. Of the 42 children, 20 (47.5%) progressed to end-stage renal failure. However, our study shows that age at onset of HUS is not a prognostic feature per se. The difference in outcome between children and infants is most likely related to the high incidence of the atypical subset of HUS in children over 3 years, a subset that is very uncommon in infants. The ominous features which characterise this form of the disease are: (1) the absence of a diarrhoeal prodrome, (2) normal urine output, (3) marked proteinuria, (4) hypertension, (5) the occurrence of relapses or recurrences and (6) the presence of widespread and severe arteriolar changes on renal biopsy. The poor prognosis of the atypical form of HUS warrants the use of fresh-frozen plasma infusions and/or plasma exchange as early as possible in the course of the disease.

Adolescent↗
PubMed1995

Detection of antilineage specific leucocyte antibodies by a quantitative immunocytometry method in sera from candidates for renal allografts.

A sensitive and quantitative flow cytometry method for detecting antileucocyte antibodies was developed to study retrospectively samples from candidates using frozen donor cells and frozen recipient sera. This immunofluorescence method was used to compare levels of reactivities of serum antibodies before and after donor specific blood transfusion treatment and after renal transplantation. The results demonstrate that the flow cytometry crossmatch is a sensitive and accurate method which should be used prospectively before precluding transplantation in the presence of a positive B cell standard crossmatch. Antibodies detected by flow cytometry before transplantation could be responsible for an early acute rejection episode. Finally, combination of flow cytometry crossmatch and standard crossmatch assays might thus be useful before precluding transplantation in living related donors.

Adolescent↗
PubMed1995

Autosomal recessive Alport syndrome: immunohistochemical study of type IV collagen chain distribution.

Alport syndrome (AS) is an hereditary disease of basement membrane collagen. It is mainly transmitted as a dominant X-linked trait and caused by mutations in the COL4A5 gene encoding the alpha 5 chain of type IV collagen. However, autosomal recessive AS due to mutations in the COL4A3 or COL4A4 genes could represent up to 15% of AS. Using the immunofluorescence technique, we analyzed the distribution of the different chains of type IV collagen in renal (12 specimens) and skin (4 specimens) basement membranes of 12 AS patients belonging to 11 unrelated kindreds in which autosomal recessive inheritance had been demonstrated (3 kindreds) or was suggested by clinical and genealogic data (8 kindreds). The renal and skin distribution was normal in one patient with COL4A4 mutations. A peculiar pattern of distribution of the alpha 3-alpha 5(IV) chains was observed in the other patients. It was characterized the co-absence of the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains in the glomerular basement membrane, and the presence of the alpha 5(IV) chain in a series of extraglomerular basement membranes including capsular, collecting ducts and epidermal basement membranes, a combination never observed in X-linked AS. This immunohistochemical pattern is correlated with the specific distribution of the alpha 3-alpha 5 chains of type IV collagen chains within extraglomerular basement membranes. It could be a useful marker for the identification of autosomal recessive AS.

Adolescent↗
PubMed1995

Mapping a gene (SRN1) to chromosome 1q25-q31 in idiopathic nephrotic syndrome confirms a distinct entity of autosomal recessive nephrosis.

Idiopathic nephrotic syndrome (INS) in childhood is characterized by massive proteinuria and minimal glomerular changes. Most patients with INS respond to steroid therapy. INS is generally regarded as a sporadic disease with favorable outcome. We investigated a distinct subgroup of nephrosis--the familial form of steroid resistant INS (SRN). These patients always progress to end-stage renal failure within a few years and show absence of recurrence of the disease after renal transplantation. The occurrence of the disorder in siblings and the high incidence of inbreeding in these families made an autosomal recessive mode of inheritance very likely. We performed whole genome linkage analysis in nine multiplex families of European or Northern African origin. Our results allowed us to assign a disease locus (SRN1) to a defined chromosomal region on 1q25-1q31, thus confirming the existence of a distinct entity of autosomal recessive nephrosis. Exclusion of linkage to the entire region in one family proves genetic heterogeneity.

Chromosome Mapping↗
PubMed1995

[Alteration of the taste for sugar in renal insufficiency: study in the child].

Children with chronic renal failure (CRF) show a reduced appetite for sweet foods. Sensory responses to sweet stimuli were investigated in 45 children with CRF, 39 dialyzed patients (HD) and 25 controls(C). Two familiar foods were prepared in 5 sucrose concentrations: 1, 5, 10, 15, 20% for soft white cheese (SWC): 10, 20, 30, 40, 60% for apple sauce (AS). When identifying the sweeter of two SWC samples, CRF(15%) and HD (18%) made more mistakes than C (5%). When testing AS, mistakes were comparable between groups (25, 21, 19%). Preferences differed according to diagnosis group. The sweetest SWC was preferred by 40% of CRF and C and by only 22% HD; the least sweet SWC was preferred by 5% of C, 10% of CRF and 16% of HD. In AS, the highest concentrations were preferred by CRF and C, median concentration by HD. Plasma zinc had no clear effect on taste. Altered preferences for sweet foods in patients suggest post-ingestive adverse effects of sucrose resulting from an altered sucrose metabolism.

Adolescent↗
PubMed1994

[Hemolytic anemia after kidney transplantation].

Several cases of haemolysis after bone marrow or organ transplantation have been reported. An allospecific anti-erythrocyte antibody has been described in each case. We report a similar case after renal transplantation. Berger's disease led to end-stage renal failure in an 18-year-old girl. During haemodialysis carried out for 6 years, the patient had received 9 transfusions of phenotyped, filtered, packed red blood cells. The recipient was grouped as O Rh positive, CcDee, Kell negative, HLA-A24 A11 B35 B-DR1 DR2. The donor was her father, grouped as O Rh negative, ccddee, Kell negative, HLA-A24 A- B35 B- DR2 DR-. Screening for erythrocyte antibodies was negative in the recipient as were screening for lymphocytotoxic antibodies and compatibility testing. However anti-D antibody was present in the donor who had received a transfusion of Rh positive blood several years before renal donation. The recipient was given 2 units of O Rh positive, phenotyped and filtered red blood cell concentrates during transplantation. Immunosuppressive therapy associated azathioprine and prednisone. The onset of graft function was immediate. Haemoglobin fell to 52 g/l on day 14 post transplantation (103 g/l on day 6). Anti-D antibody was identified in the serum. The direct antiglobulin test was positive with anti-IgG, antiglobulin and the eluate contained an antibody exhibiting also anti-D specificity. The anti-D of the patient and the donor had the same Gm allotyping. The outcome was favourable though the antibody was persistent for several months. This case of haemolysis is consistent with the fact that immunocompetent B lymphocytes transferred with the grafted organ are still able to produce clinically significant antibodies.

Adolescent↗