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C Antignac

Publications and source records attributed to C Antignac.

15 recordsLinked to original sources
PubMed1992

Alport syndrome and diffuse leiomyomatosis: deletions in the 5' end of the COL4A5 collagen gene.

Alport syndrome (AS) is an hereditary glomerulonephritis that is mainly inherited as a dominant X-linked trait. Structural abnormalities in the type IV collagen alpha 5 chain gene (COL4A5), which maps to Xq22, have recently been detected in several patients with AS. The association of AS with diffuse esophageal leiomyomatosis (DL) has been reported in 24 patients, most of them also suffering from congenital cataract. The mode of transmission and the location of the gene(s) involved in this association have not been elucidated. Southern blotting using cDNA probes spanning the whole COL4A5 and a 5' end COL4A5 genomic probe showed that three out of three patients with the DL-AS association had a deletion in the 5' part of the COL4A5 gene extending beyond its 5' end. This indicates that the same gene, COL4A5, is involved in classical AS and in DL-AS and that the transmission of DL-AS is X-linked dominant. These results also suggest that leiomyomatosis might be due to the alteration of a second gene involved in smooth muscle cell proliferation, which is located upstream of the COL4A5 gene, and that there might be a contiguous gene deletion syndrome, involving at least the genes coding for congenital cataract, DL and AS.

Adolescent↗
PubMed1992

Substitution of arginine for glycine 325 in the collagen alpha 5 (IV) chain associated with X-linked Alport syndrome: characterization of the mutation by direct sequencing of PCR-amplified lymphoblast cDNA fragments.

A large kindred with adult-type X-linked Alport syndrome was studied with regard to a defect in the recently described COL4A5 collagen gene. Southern blot analysis with COL4A5 cDNA probes showed loss of a MspI restriction site. Direct sequencing of cDNA amplified from lymphoblast mRNA demonstrated a single-base substitution converting a glycine codon to arginine at position 325 in the alpha 5 chain of type IV collagen. The triple-helical collagenous domain of alpha 5(IV), characterized by a Gly-X-Y repeat sequence, is interrupted 22 times by noncollagenous sequences. The mutation creates an additional interruption in the Gly-X-Y repeat motif, between interruptions 4 and 5. It is interesting that such glycine substitutions inside the COL1A1 or COL1A2 genes have been associated with many cases of osteogenesis imperfecta. This gly325-to-arg substitution presumably alters the triple-helix formation, and, in turn, modifies the ultrastructural and functional characteristics of the type IV collagen network inside the glomerular basement membrane.

Adult↗
PubMed1991

A gene for limb-girdle muscular dystrophy maps to chromosome 15 by linkage.

Limb-girdle muscular dystrophy (LGMD) is inherited as a monogenic, autosomal recessive trait. A genetically homogeneous group of families from the Isle of La Réunion, comprising individuals at high risk for this disorder, was systematically analysed using a panel of 85 polymorphic markers spanning approximately 30% of the human genome. Linkage was detected between the LGMD gene and the marker D15S25, uncovered with the probe pTHH114 and restriction enzyme RsaI (lod score = 5.52 at a 0 = 0.0), localising this gene onto chromosome 15. Such a lod score corresponds to odds of 3.3 x 105 in favor of linkage versus absence of linkage. Additional families from other populations will need to be examined before the role of this newly identified locus can be understood.

Chromosome Mapping↗
PubMed1991

[Antioncogenes: models for tumors in children].

The chromosomal assignment of genes responsible for malformation syndromes associated with increased susceptibility to malignancy could be determined owing to specific constitutional chromosomal abnormalities or to family studies. For certain types of tumors, somatic chromosomal rearrangements (loss of alleles) occur at the same locus indicating the presence of a recessive suppressor gene or an antioncogène. For other types of tumors chromosomal rearrangements involving regions different from the locus for predisposition suggest genetic heterogeneity and/or implication of genes for tumor progression. These genes which are also involved in development and regulation of differentiation and cell growth, may undergo a differential genomic imprinting.

Alleles↗
PubMed1990

Renal functional reserve in children with reduced renal mass: study by two dietary periods.

It has been suggested that the "renal functional reserve" (RFR) defined by the rise in glomerular filtration rate (GFR) after a protein load could disappear in patients with severe nephron loss but with a normal GFR. This study compared, in 17 children, inulin clearance (Cin) measured by the plasma inulin plateau at the end of two 14-day randomized periods differing in protein intake: 100% (low protein, LP), or 200% (high protein, HP) of recommended dietary allowances (RDA). Diets were aimed at maintaining food habits and energy intake. Compliance was assessed by records of the last 3-4 days, an interview with the dietician and by urinary nitrogen measurements. Mean actual protein intake was 109% (56%-139%) RDA for the LP period and 220% (163%-319%) RDA for the HP period. Cin did not change in 14 children with GFR below (n = 7) or within (n = 7) the normal range. Cin was higher in the HP period than in the LP period (+32, 50, 63%) in 3 children who had a 50% (single kidneys) or a 25% (sclerosed glomeruli) nephron loss. Non-responding children had a GFR below 105 ml/min per 1.73 m2. Nephron loss (70% sclerosed glomeruli) was estimated in only 1 child with no RFR. The results suggest that GFR measurement after prolonged dietary stimulation could help in evaluating the severity of nephron loss in children with normal or borderline GFR. The prognostic value of this test has to be confirmed by long-term follow-up.

Adolescent↗
PubMed1990

Constitutional and somatic deletions of two different regions of maternal chromosome 11 in Wilms tumor.

Loss of heterozygosity for 11p markers and preferential loss of maternal alleles have been described in Wilms tumor. In this report we describe the molecular characterization of the constitutional and somatic 11p rearrangements in a del(11p13) WAGR patient with Wilms tumor. Both rearrangements led to loss of maternal alleles for two different regions of 11p, namely, 11p13 and 11p14----p15. This result clearly suggests that Knudson's hypothesis of two hits at the same locus does not necessarily apply to Wilms tumor. Moreover, the loss of 11p15 maternal alleles in the tumor is not incompatible with maternal inheritance of predisposition at 11p13. The putative roles of these two loci are discussed.

Alleles↗
PubMed1990

[Congenital or childhood nephrotic syndrome with diffuse mesangial sclerosis].

Diffuse mesangial sclerosis (DMS) has been described as a distinct morphological pattern observed in patients presenting with a congenital or infantile nephrotic syndrome (NS) leading to end stage renal failure (ESRF) before the age of 3 years (Habib & Bois: Helv. Peadiat. Acta 28: 91-107, 1973). In recent years, we diagnosed this entity in 36 infants and we wish to report our findings which extend our previous observations. The nephropathy was discovered before 1 year of age in 26 patients. In one of these the onset was neonatal. Five additional children were between 1 and 2 years of age at onset of the disease and the remaining 5 were between 24 and 42 months old. Thirty-three patients presented with a NS often preceded by a proteinuria and associated with renal failure in 6 of them. The 3 remaining patients presented with renal failure. Thirty-one patients reached ESRF before the age of 4 years. Progression was slower in 5 patients who were respectively 5, 5, 6, 8 and 11 years old at ESRF. Thirteen patients were transplanted and none recurred their original disease. Seven patients in 4 families had similarly affected siblings. In 16 patients (6 boys and 10 girls) the nephropathy was isolated. In the remaining 20 several associated findings were noted. In 14 infants a diagnosis of Drash syndrome was made on the basis of the association of a male pseudo-hermaphroditism (PsH) and Wilms tumour (WT) in 5, of a male PsH in 5 additional infants and of a WT in 4 female patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1990

[Kidney functional reserve. Studies in humans].

The glomerular filtration rate (GF) of each nephron can vary, with increases being caused by stimuli such as nephron reduction and ingestion of proteins. This "functional reserve" (FR), detectable by protein load tests, may be lost in extensive renal destruction where the remaining nephrons are in a permanent state of maximal stimulation. If this hypothesis is true, FR determinations would be of greater value than baseline GFR measurements for evaluating the condition of the remaining parenchyma. A very large number of studies have addressed the FR in normal subjects and have used either diets containing variable amounts of proteins or acute loads given orally (approximately 1 g/kg cooked meat) or intravenously (amino acids). All these studies have evidenced increases in the GFR after the load, regardless of its type, but with major variations across studies and patients. Subjects with a single healthy kidney seem to retain a FR whose magnitude is equal to or smaller than the FR in normal subjects. Conflicting data have been reported in more extensive destruction of the parenchyma, where the FR has been shown to either disappear or persist with no change in percentage. Thus, the practical value of GFR determinations after protein loads has not as yet been established and should be specified using better standardized methods that do not rely on creatinine clearance, at least during oral load tests where serum creatinine levels increases and is no longer stable.

Child↗
PubMed1989

Delayed renal failure with extensive mesangiolysis following bone marrow transplantation.

Within two years we have had the opportunity of observing seven leukemic children who were referred to our Pediatric Nephrology Unit for delayed renal failure following bone marrow transplantation (BMT). These children (3 to 12 years old), six with acute lymphoblastic leukemia (ALL) and one with acute non-lymphoblastic leukemia (ANLL), underwent BMT (4 autologous BMT, 3 allogeneic BMT) after the first remission in two, and after the second remission in five. Preparative regimen for BMT included cyclosphosphamide in three, cyclosphosphamide, vepeside and cytosine A in four, and a total body irradiation in a single dose of 10 grays (1000 R) in all of them. Three children were treated immediately after grafting with low dose cyclosporine for four to six months. Five to 10 months after BMT, four patients developed a hemolytic uremic syndrome with severe hypertension. The remaining three were found to have isolated renal insufficiency several months post-BMT. In the seven patients, renal biopsy showed a uniform pattern of severe glomerular involvement characterized by extensive lesions of mesangiolysis associated with severe arteriolonecrosis. A repeat biopsy performed one year later, in two patients showed severe scarring of the renal parenchyma with minor lesions of mesangiolysis. The similarity of the pathologic features observed suggests that the same mechanism might have been operative in the seven patients. It is very likely that the nephropathy is related to total body irradiation enhanced by chemotherapy. We conclude that current treatments of high risk leukemia might become a new cause of chronic renal failure. Further investigations are needed to know the exact incidence of this complication.

Bone Marrow Transplantation↗
PubMed1988

De novo membranous glomerulonephritis in renal allografts in children.

The incidence of de novo membranous glomerulonephritis (MGN) in transplanted kidneys is around 1 to 2%. In our series, of the 310 grafts that were examined by immunofluorescence microscopy (IF), 29 (9.3%) showed subepithelial IgG deposits, a pattern consistent with the diagnosis of MGN. Transplant biopsy had been performed because of the occurrence of proteinuria in 8 patients (pts), for suspected rejection in 16 and systematically in the remaining 9 who had no proteinuria and a normal renal function. In all cases the lesions were identified by IF and were confirmed by electron microscopy (EM) in 14 pts. Granular deposits of IgG were diffuse in 22 cases and segmental in 7. Sequential specimens were available in 17 pts and showed the persistence or the increase of the IgG deposits in all patients but one in whom they had disappeared. Age at transplantation (Tx) ranged from 2 years 3 months to 16 years. Grafts were from cadaveric donors in 27 pts and from living related donors in 2 pts. In none of the recipients was MGN the nephropathy of the native kidneys. With a follow-up of 18 to 74 months, 6 pts never developed a proteinuria. In the remaining 23, proteinuria developed 1 to 70 months after Tx, associated with a nephrotic syndrome (NS) in 6 pts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Glomerular lesions in the transplanted kidney in children.

The glomerular pathology of 634 transplant specimens (526 biopsies and 108 transplantectomies) from 410 children was studied. Three types of glomerulopathies were observed: (1) recurrent glomerulonephritis (GN) (40 of 142 patients with glomerular nephropathy), (2) de novo GN (52 grafts), and (3) transplant glomerulopathy (29 grafts). The study of recurrent GN is considered of great interest because of the possible insight into the nature of the original disease and the opportunity to observe the evolution of the disease in sequential biopsies of the transplant. The two major forms of de novo GN were membranous GN and IgG linear deposits along glomerular and tubular basement membranes. Transplant glomerulopathy, although distinctive morphologically, may resemble membranoproliferative GN (MPGN) or thrombotic microangiopathy.

Biopsy↗
PubMed1985

[Diffuse arterial calcified elastopathy].

Diffuse arterial calcified elastopathy was observed in 6 pediatric patients presenting with severe renovascular hypertension. Renal ultrasonography showed a characteristic pattern, the dotted corticomedullary junction, related to the increased echogenicity of the interlobar and/or arcuate arteries. Superficial temporal artery biopsy demonstrated the presence and the extension of the calcifying process involving the elastic layers of the muscular arteries. This clinicopathological syndrome may be heterogeneous from an etiological point of view: etiologic investigations led to the diagnosis of pseudoxanthoma elasticum in 2 patients; no etiology could be found in the others.

Arteries↗
PubMedDate not supplied

[Pharmacokinetics of prednisone after oral administration in children with renal grafts. Changes induced by phenobarbital and renal insufficiency].

A study of blood and urinary clearance of prednisone after ingestion of a 25 mg/m2 body surface test-dose, at 8 AM, was undertaken in 20 children treated for 18 months with prednisone after renal transplant. Results show important variability between patients: the elimination half life was 2.70 +/- 0.78 hr.; Tmax time to reach Cmax was 2.10 +/- 1.08 hr.; Maximal concentration (Cmax) was 474 +/- 153 ng/ml. With respect to the dose of steroid administered, the urinary excretion of corticosteroids: 17-hydroxycorticosteroids was 12.9 +/- 7.4% and that of unchanged prednisolone 2.8 +/- 3.1%. This level was essentially achieved in the 6 first hours: 55.4 +/- 16.2% for 17-OH steroids and 87.2 +/- 14.3% for prednisolone. Two points emerge from this study: (a) Renal failure slows urinary excretion of prednisone and its metabolites, making a reduction in the doses of corticosteroids necessary at certain doses. (b) The association prednisone-phenobarbital changes the blood kinetics (excretion is faster) without a clear change in 17-OH steroid and prednisolone urinary excretion. It is associated with a decrease in graft tolerance. The kinetic changes do not seem to be the only factors implicated in the decreased therapeutic response.

Administration, Oral↗
PubMedDate not supplied

Diffuse arterial calcified elastopathy--a new cause of renovascular hypertension in children.

Diffuse arterial calcified elastopathy was observed in 6 pediatric patients presenting with severe renovascular hypertension. Renal ultrasonography showed a characteristic pattern, the dotted corticomedullary junction, related to the increased echogenicity of the interlobar and/or arcuate arteries. Superficial temporal artery biopsy demonstrated the presence and the extension of the calcifying process involving the elastic layers of the muscular arteries. This clinicopathological syndrome may be heterogeneous from an etiological point of view: etiologic investigations led to the diagnosis of pseudoxanthoma elasticum in 2 patients; no etiologic cause could be found in the others.

Arterial Occlusive Diseases↗