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C Piussan

Publications and source records attributed to C Piussan.

At least 19 recordsLinked to original sources
PubMed1996

Toward localization of the Werner syndrome gene by linkage disequilibrium and ancestral haplotyping: lessons learned from analysis of 35 chromosome 8p11.1-21.1 markers.

Werner syndrome (WS) is an autosomal recessive disorder characterized by premature onset of a number of age-related diseases. The gene for WS, WRN, has been mapped to the 8p 11.1-21.1 region with further localization through linkage disequilibrium mapping. Here we present the results of linkage disequilibrium and ancestral haplotype analyses of 35 markers to further refine the location of WRN. We identified an interval in this region in which 14 of 18 markers tested show significant evidence of linkage disequilibrium in at least one of the two populations tested. Analysis of extended and partial haplotypes covering 21 of the markers studied supports the existence of both obligate and probable ancestral recombinant events which localize WRN almost certainly to the interval between D8S2196 and D8S2186, and most likely to the narrower interval between D8S2168 and D8S2186. These haplotype analyses also suggest that there are multiple WRN mutations in each of the two populations under study. We also present a comparison of approaches to performing disequilibrium tests with multiallelic markers, and show that some commonly used approximations for such tests perform poorly in comparison to exact probability tests. Finally, we discuss some of the difficulties introduced by the high mutation rate at microsatellite markers which influence our ability to use ancestral haplotype analysis to localize disease genes.

Age of Onset↗
PubMed1995

X-linked progressive mixed deafness: a new microdeletion that involves a more proximal region in Xq21.

We report a large two-generation pedigree with seven affected males segregating for an X-linked mixed conductive sensorineural deafness. The patients present with atypical Mondini-like dysplasia, dilated petrous facial canal, dilatation of the internal auditory meatus fully connected with enlarged cochlear canals, and, in one patient, a wide bulbous posterior labyrinth. Obligatory carrier females are mildly affected. Molecular characterization of this family revealed a deletion of locus DXS169, in Xq21.1. Loci DXS72 and DXS26, which, respectively, flank DXS169 proximally and distally, were intact. Since a gene responsible for X-linked progressive mixed deafness with perilymphatic gusher (DFN3) has previously been assigned by deletion mapping to a slightly more distal interval between DXS26 and DXS121, this study indicates either two different deafness genes or the involvement of a very large region in Xq21.

Ear, Inner↗
PubMed1995

Hypokalemic periodic paralysis and the dihydropyridine receptor (CACNL1A3): genotype/phenotype correlations for two predominant mutations and evidence for the absence of a founder effect in 16 caucasian families.

Hypokalemic periodic paralysis (hypoPP) is an autosomal dominant disorder belonging to a group of muscle diseases involving the abnormal function of ion channels. This group of muscle diseases also comprises hyperkalemic periodic paralysis and paramyotonia congenita, both sodium-channel diseases, and myotonia congenita, a chloride-channel disorder. HypoPP is characterized by acute attacks of muscle weakness concomitant with a fall in blood potassium levels. We recently localized the hypoPP locus (hypoPP1) to chromosome 1q31-32, in an interval where the alpha 1 subunit of the dihydropyridine receptor calcium channel (CACNL1A3) also maps. Subsequently, deleterious mutations in the voltage-sensor segment S4 were found, establishing the dihydropyridine receptor CACNL1A3 as the causative gene for hypoPP. In this paper, we report the study of 16 hypoPP families of Caucasian origin. We found only two mutations--Arg528His and Arg1239His--that cosegregated with hypoPP, each in half of the families. Analysis of the clinical characteristics of both groups of families demonstrated that incomplete penetrance is a distinctive feature of the Arg528His mutation. Using dinucleotide repeats contained within or close to the dihydropyridine receptor gene, in conjunction with evidence of a de novo Arg1239His mutation, we show that a founder effect is unlikely to account for the two predominant mutations.

Arginine↗
PubMed1994

Homozygosity mapping of the Werner syndrome locus (WRN).

Werner syndrome (WS) is an autosomal recessive disorder characterized by the early onset of several age-related diseases. The locus for this disease was recently mapped to 8p12. We studied 27 WS kindreds of mixed ethnic origins, 26 of which were consanguineous. In 24 of these families, the affected subject was given the diagnosis of "definite" WS and affected subjects in the remaining 3 pedigrees were given the diagnosis of "probable" WS. Affected subjects from each kindred were genotyped for 13 short tandem repeat polymorphic sites. Two-point linkage analysis yielded significant evidence for linkage to D8S137, D8S339, D8S87, PLAT, D8S165, and D8S166. The locus yielding a maximum lod score at the smallest recombination fraction was D8S339, suggesting that this marker is the closest to the WS gene (WRN locus) of those tested. D8S339 gave significant lod scores (Zmax > or = 3.0) for both Japanese and non-Japanese (mostly Caucasian) families, demonstrating that a single locus is responsible for WS in both groups. Multipoint analysis of these markers yielded a maximum lod score of 17.05 at a distance of approximately 0.6 cM from D8S339. The combined evidence from 2-point analysis, multipoint analysis, and analysis of regions of homozygosity in subjects from inbred pedigrees indicates that the WRN locus is between D8S131 and D8S87, in an 8.3-cM interval containing D8S339.

Alleles↗
PubMed1994

The gene for the familial form of incontinentia pigmenti (IP2) maps to the distal part of Xq28.

Linkage data for familial incontinentia pigmenti (IP2) and 17 X chromosomal markers are reported. The linkage previously found between IP2 and the F8C locus is confirmed (Z max = 11.85 at theta = 0.028). Linkage is established with distal markers DXS1108 (Z max = 10.06 at theta = 0.00) and DXYS154 (Z = 9.07 at theta = 0.019). Multipoint analysis supports the distal localization of the IP2 gene with respect to the F8C locus.

Animals↗
PubMed1994

Linkage disequilibrium and haplotype studies of chromosome 8p 11.1-21.1 markers and Werner syndrome.

Werner syndrome (WS) is an autosomal recessive disorder, characterized as a progeroid syndrome, previously mapped to the 8p 11.1-21.1 region. Because WS is so rare, and because many patients are from consanguineous marriages, fine localization of the gene by traditional meiotic mapping methods is unlikely to succeed. Here we present the results of a search for a region that exhibits linkage disequilibrium with the disorder, under the assumption that identification of such a region may provide an alternative method of narrowing down the location of WRN, the gene responsible for WS. We present allele frequencies in Japanese and Caucasian cases and controls for D8S137, D8S131, D8S87, D8S278, D8S259, D8S283, fibroblast growth factor receptor 1, ankyrin 1, D8S339, and two polymorphisms in glutathione reductase (GSR), covering approximately 16.5 cM in total. We show that three of the markers examined--D8S339 and both polymorphisms in the GSR locus--show strong statistically significant evidence of disequilibrium with WRN in the Japanese population but not in the Caucasian population. In addition, we show that a limited number of haplotypes are associated with the disease in both populations and that these haplotypes define clusters of apparently related haplotypes that may identify as many as eight or nine independent WRN mutations in these two populations.

Ankyrins↗
PubMed1993

A familial syndrome with micrognathia, cleft palate, short neck and stature, vertebral anomalies and mental retardation.

We report on a male adult and his son both affected with hitherto undescribed multiple congenital anomalies and mental retardation. Both have peculiar facies, cleft palate, short sature, congenital brevicollis and vertebral abnormalities. Chromosomal analysis is normal and an autosomal dominant mode of inheritance is most likely. Genetic aspects and clinical manifestations are compared with those of previous reports of Robin sequence or cleft palate, short stature and vertebral dysostosis.

Abnormalities, Multiple↗
PubMed1993

[Neisseria mucosa endocarditis complicated by intracerebral aneurysm].

BACKGROUND: Serious complications, such as emboli and mycotic aneurysms, are still frequent in documented cases of infective endocarditis. Infecting organisms other than Streptococcus viridans and Staphylococcus are becoming more common. CASE REPORT: A 8 year-old girl was admitted because of a sudden pain in the right calf followed by complete disability. She had low-grade fever and presented with a moderate heart murmur with no sign of congestive heart failure, a severe pain at palpation of her calf with no Homans sign; she had many dental caries. Laboratory data indicated leukocytosis with increased percentage of polymorphonuclear cells and increased sedimentation rate. Ultrasonography of the calf showed laceration of the muscle with blood suffusion. Echocardiography showed vegetations involving the mitral valve. Intravenous antibiotic therapy with penicillin G and netilmicin was instituted, but mitral insufficiency appeared 7 days later while the fever persisted. At that time, the brain CT scan showed ischemic lesions, while angiography showed several mycotic aneurysms. Neisseria mucosa was recovered from the 5 initial blood cultures 16 days after the onset, and penicillin G was replaced by ampicillin. A second vegetation involving the aortic valve was seen a few days later, and a recent arterial embolism to the right leg was suspected because fever and pain reappeared. The brain ischemic lesions gradually disappeared and a second angiography performed 3 months after the first showed that all but one large mycotic aneurysm had disappeared; this last aneurysm was excised. Four years later, the child is in good health without any neurological sequelae but having mitral insufficiency. CONCLUSION: This girl presented with classical complication of infective endocarditis due to Neisseria mucosa, a saprophytic organism of the oral cavity. This is the second report of such an infection in children.

Ampicillin↗
PubMed1993

The Juberg-Marsidi syndrome maps to the proximal long arm of the X chromosome (Xq12-q21).

Juberg-Marsidi syndrome (McKusick 309590) is a rare X-linked recessive condition characterized by severe mental retardation, growth failure, sensorineural deafness, and microgenitalism. Here we report on the genetic mapping of the Juberg-Marsidi gene to the proximal long arm of the X chromosome (Xq12-q21) by linkage to probe pRX214H1 at the DXS441 locus (Z = 3.24 at theta = .00). Multipoint linkage analysis placed the Juberg-Marsidi gene within the interval defined by the DXS159 and the DXYS1X loci in the Xq12-q21 region. These data provide evidence for the genetic distinction between Juberg-Marsidi syndrome and several other X-linked mental retardation syndromes that have hypogonadism and hypogenitalism and that previously. Finally, the mapping of the Juberg-Marsidi gene is of potential interest for reliable genetic counseling of at-risk women.

Abnormalities, Multiple↗
PubMed1992

Confirmation and refinement of the genetic localization of the Coffin-Lowry syndrome locus in Xp22.1-p22.2.

The Coffin-Lowry syndrome (CLS) is an X-linked inherited disease of unknown pathogenesis characterized by severe mental retardation, typical facial and digital anomalies, and progressive skeletal deformations. Our previous linkage analysis, based on four pedigrees with the disease, suggested a localization for the CLS locus in Xp22.1-p22.2, with the most likely position between the marker loci DXS41 and DXS43. We have now extended the study to 16 families by using seven RFLP marker loci spanning the Xp22.1-p22.2 region. Linkage has been established with five markers from this part of the X chromosome: DXS274 (lod score [Z] (theta) = 3.53 at theta = .08), DXS43 (Z(theta) = 3.16 at theta = .08), DXS197 (Z(theta) = 3.03 at theta = .05), DXS41 (Z(theta) = 2.89 at theta = .08), and DXS207 (Z(theta) = 2.73 at theta = .13). A multipoint linkage analysis further placed, with a maximum multipoint Z of 7.30, the mutation-causing CLS within a 7-cM interval defined by the cluster of tightly linked markers (DXS207-DXS43-DXS197) on the distal side and by DXS274 on the proximal side. Thus, these further linkage data confirm and refine the map location for the gene responsible for CLS in Xp22.1-p22.2. As no linkage heterogeneity was detected, this validates the use of the Xp22.1-p22.2 markers for carrier detection and prenatal diagnosis in CLS families.

Abnormalities, Multiple↗
PubMed1991

Statistical approaches for the detection of heterozygotes for biotinidase deficiency.

We applied and evaluated 3 statistical approaches for the detection of heterozygotes for biotinidase deficiency in a randomly selected population of French adults. The first method, which used a cutoff value to dichotomize the population, lacked sensitivity. The second approach calculated the probability of heterozygosity for a given enzyme activity through the application of Bayes theorem to the normal density functions of the enzyme distributions of the obligate heterozygote and the test populations. A priori values of the means and standard deviations (SDs) of the genotypic distributions were used. This method was sufficiently sensitive for both population screening and genetic counseling, but requires prior knowledge of the frequency of the deficient gene (q). The third approach was similar to the second, however, maximum likelihood estimates of the means and SDs of the genotypic distributions were calculated and used to determine the probability of heterozygosity for a given enzyme activity. This method was as sensitive as the second method and is appropriate for screening populations for which there is little prior information about the gene frequency and the genotypic distributions. This method can also be used to estimate the gene frequency of the disorder within a given ethnic or racial population. Using this method, we estimated the frequency of heterozygotes (2pq) in the French population to be 0.012, which was similar to that estimated from the results of neonatal screening for biotinidase deficiency. These methods can be used to detect heterozygotes and to estimate the gene frequency of other inherited enzyme deficiencies.

Amidohydrolases↗
PubMed1991

Trichomegaly, pigmentary degeneration of the retina and growth disturbances. A probable autosomal recessive disorder.

Two brothers are described with trichomegaly, early pigmentary degeneration of the retina, growth retardation, anterior pituitary deficiencies and peripheral neuropathy. This syndrome, initially reported in a boy by Olivers and Mac Farlane in 1965 (6), and thereafter in six sporadic cases of both sexes, is not associated with a recognizable chromosomal defect. The present report of two brothers of healthy parents with negative familial history suggests an autosomal recessive mode of inheritance of this entity.

Adult↗
PubMed1991

[Dubowitz syndrome. A diagnosis not to be missed].

Dubowitz syndrome is a rare hereditary disorder whose main features are intra-uterine and post-natal growth retardation, characteristic facies, microcephaly, mental retardation and poor feeding. Because of the eczema which was present in half of the cases after 4 years of age, it cannot be mistaken for the more frequent fetal alcohol syndrome. We report 5 cases, among whom two sibs, confirming the recessive autosomal mode of inheritance and the necessity for genetic counseling.

Abnormalities, Multiple↗