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Biomedical subjects

Yves Pirson

Publications and source records attributed to Yves Pirson.

25 records · Page 2Linked to original sources
PubMed2001

Familial juvenile hyperuricemic nephropathy and autosomal dominant medullary cystic kidney disease type 2: two facets of the same disease?

Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder heralded by hyperuricemia during childhood; it is characterized by chronic interstitial nephritis, with marked thickening of tubular basement membranes, and leads to progressive renal failure during adulthood. A gene for FJHN in two Czech families was recently mapped to chromosome 16p11.2, close to the MCKD2 locus, which is responsible for a variant of autosomal dominant medullary cystic kidney disease observed in an Italian family. In a large Belgian family with FJHN, a tight linkage between the disorder and the marker D16S3060, located within the MCKD2 locus on chromosome 16p12 (maximal two-point logarithmic odds score of 3.74 at a recombination fraction of theta = 0), was observed in this study. The candidate region was further narrowed to a 1.3-Mb interval between D16S501 and D16S3036. Together with the striking clinical and pathologic resemblance between previously reported medullary cystic kidney disease type 2 and FJHN occurring in the Belgian family (including the presence of medullary cysts), this study suggests that these two disorders are facets of the same disease.

Adolescent↗
PubMed2000

CF gene and cystic fibrosis transmembrane conductance regulator expression in autosomal dominant polycystic kidney disease.

Disease-modifying genes might participate in the significant intrafamilial variability of the renal phenotype in autosomal dominant polycystic kidney disease (ADPKD). Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is a chloride channel that promotes intracystic fluid secretion, and thus cyst progression, in ADPKD. The hypothesis that mutations of the CF gene, which encodes CFTR, might be associated with a milder renal phenotype in ADPKD was tested. A series of 117 unrelated ADPKD probands and 136 unaffected control subjects were screened for the 12 most common mutations and the frequency of the alleles of the intron 8 polymorphic TN: locus of CF. The prevalence of CF mutations was not significantly different in the ADPKD (1.7%, n = 2) and control (3.7%, n = 5) groups. The CF mutation was DeltaF508 in all cases, except for one control subject (1717-1G A). The frequencies of the 5T, 7T, and 9T intron 8 alleles were also similar in the ADPKD and control groups. Two additional patients with ADPKD and the DeltaF508 mutation were detected in the families of the two probands with CF mutations. Kidney volumes and renal function levels were similar for these four patients with ADPKD and DeltaF508 CFTR (heterozygous for three and homozygous for one) and for control patients with ADPKD collected in the University of Colorado Health Sciences Center database. The absence of a renal protective effect of the homozygous DeltaF508 mutation might be related to the lack of a renal phenotype in CF and the variable, tissue-specific expression of DeltaF508 CFTR. Immunohistochemical analysis of a kidney from the patient with ADPKD who was homozygous for the DeltaF508 mutation substantiated that hypothesis, because CFTR expression was detected in 75% of cysts (compared with <50% in control ADPKD kidneys) and at least partly in the apical membrane area of cyst-lining cells. These data do not exclude a potential protective role of some CFTR mutations in ADPKD but suggest that it might be related to the nature of the mutation and renal expression of the mutated CFTR.

Adult↗
PubMed2000

X-linked Alport syndrome: natural history in 195 families and genotype- phenotype correlations in males.

Alport syndrome (AS) is a type IV collagen hereditary disease characterized by the association of progressive hematuric nephritis, hearing loss, and, frequently, ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease. Considerable allelic heterogeneity has been observed. A "European Community Alport Syndrome Concerted Action" has been established to delineate accurately the AS phenotype and to determine genotype-phenotype correlations in a large number of families. Data concerning 329 families, 250 of them with an X-linked transmission, were collected. Characteristics of the 401 male patients belonging to the 195 families with COL4A5 mutation are presented. All male patients were hematuric, and the rate of progression to end-stage renal failure and deafness was mutation-dependent. Large deletions, non-sense mutations, or small mutations changing the reading frame conferred to affected male patients a 90% probability of developing end-stage renal failure before 30 yr of age, whereas the same risk was of 50 and 70%, respectively, in patients with missense or splice site mutation. The risk of developing hearing loss before 30 yr of age was approximately 60% in patients with missense mutations, contrary to 90% for the other types of mutations. The natural history of X-linked AS and correlations with COL4A5 mutations have been established in a large cohort of male patients. These data could be used for further evaluation of therapeutic approaches.

Adult↗
PubMedDate not supplied

From renal amyloid deposits to the identification of the culprit genes.

Hereditary amyloidoses with renal involvement are classified in two groups. The first group is a growing family of autoinflammatory disorders characterized by recurrent fever attacks. Amyloidosis is caused by the deposition of amyloid A (AA) protein, which is a degradation product of a normal serum acute-phase protein: serum amyloid A (SAA). The prototype is familial Mediterranean fever (FMF). TNF Receptor Associated Periodic Syndrome (TRAPS) is a recently recognized periodic fever syndrome, differing from FMF in several characteristics: autosomal-dominant transmission, longer duration of attacks, and lack of response to colchicine prophylaxis. The second group comprises a variety of disorders, each characterized by the deposition of a specific mutant protein. The prototype is transthyretin amyloidosis (TTR). Identification of the form of amyloidosis has clinical implications. Therefore, in a patient with a history of recurrent fever attacks and AA amyloidosis, a diagnosis of FMF or TRAPS dictates appropriate genetic counseling and management. In patients with renal amyloidosis without a history of fever, identification of the mutant protein is therapeutically crucial; therefore, when the cell type that produces the precursor is (exclusively or mainly) the hepatocyte, a liver transplantation is to be considered.

Amyloidosis↗