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Biomedical subjects

I Richard

Publications and source records attributed to I Richard.

At least 73 records · Page 4Linked to original sources
PubMed1996

Chromosome 15-linked limb-girdle muscular dystrophy: clinical phenotypes in Reunion Island and French metropolitan communities.

Erb's type limb-girdle muscular dystrophy (LGMD) was identified and clinically studied in detail in a small community living in the Reunion Island (RI). It was linked to chromosome 15q and related to mutations in the muscle specific calpain 3 gene. A series of cases were afterwards clinically and genetically identified in the French metropolitan community. The phenotype was identical to the RI type in the great majority of cases, although clinical differences were noticed in a few cases. Six different mutations were identified in the RI families, whereas a series of 39 mutations were detected in the French metropolitan families, all different from those present in the RI patients. Phenotype-genotype correlations were attempted in both communities.

Adolescent↗
PubMed1996

Juvenile limb-girdle muscular dystrophy. Clinical, histopathological and genetic data from a small community living in the Reunion Island.

A series of patients affected by a muscular dystrophy, similar to the original description of a juvenile scapulo-humeral form by Erb in 1884 and fitting with the criteria used to define limb-girdle muscular dystrophies, was discovered in a small community living in the southern part of Reunion Island in the Indian Ocean. A detailed clinical analysis was conducted over 5 years on a cohort of 20 patients. This community presented a high degree of consanguinity as it was segregated from the majority of the island population for more than a century. In previous molecular genetic studies, the disease locus has been mapped to chromosome 15p. Mutations were recently identified in a gene located in this region encoding for muscle-specific calcium activated neutral protease (CANP3). Clinical, pathological, genetic and complete identification of the mutations are presented here, establishing, for the first time, precise clinico-genetic correlations in this form of autosomal recessive, juvenile, limb-girdle muscular dystrophy (LGMD).

Adolescent↗
PubMed1996

Role of magnetic resonance imaging in the diagnosis and prognosis of growth hormone deficiency.

OBJECTIVE: In patients with congenital GH deficiency (GHD), magnetic resonance imaging (MRI) has revealed morphological abnormalities such as pituitary hypoplasia, absence of the stalk and ectopia of the posterior pituitary (PPE). Our study was aimed at investigating the possible relationship between neuroradiological images and the presence of isolated GH or multiple pituitary hormone deficiency. DESIGN: We studied 121 patients, aged 0.3-25 years, with isolated GHD (IGHD, 81 cases) or multiple pituitary hormone deficiency (MPHD, 40 cases). Of 81 IGHD patients, 50 were at prepubertal and 22 at pubertal age, while 9 had a delayed onset of puberty. Out of 40 MPHD patients, 25 were at prepubertal age and 15 at the age of puberty. RESULTS: Pituitary hypoplasia, defined as a gland with a height of less than -2 SD for age, was observed more frequently in prepubertal (66%) than pubertal (18%) IGHD patients. It was also found in the majority of MPHD patients of prepubertal (76%) and pubertal age (80%), and of IGHD patients with delayed onset of puberty (100%). Mean +/- SEM pituitary height was significantly lower (P < 0.001) in both prepubertal IGHD (-2.70 +/- 0.20 SD) and MPHD children (-3.10 +/- 0.39 SD) than in IGHD patients with normal onset of puberty (-1.55 +/- 0.2 SD). A significantly greater pituitary height was observed in IGHD patients with normal onset of puberty (-1.55 +/- 0.20 SD) than in MPHD patients at the age of puberty (-4.38 +/- 0.61 SD, P < 0.001) and in IGHD subjects with delayed onset of puberty (-4.06 +/- 0.41 SD, P < 0.001). An important increase (P < 0.02) in the height of the pituitary gland was found in 6 of the 9 patients with delayed puberty when they were re-evaluated after completing their spontaneous pubertal development. The frequency of other MRI abnormalities (PPE, stalk transection) was significantly higher in MPHD patients than in IGHD patients (P < 0.001). CONCLUSION: Our results confirm the usefulness of MRI in the evaluation of children affected by GH deficiency. The association of gland hypoplasia with other MR abnormalities could suggest the presence of multiple anterior pituitary deficiencies. Finally, puberty seems to play an important role in the increase of pituitary size in multiple pituitary hormone deficiency and isolated GH deficiency patients.

Adolescent↗
PubMed1996

Highly conserved structure in the promoter region of the gene for muscle-specific calpain, p94.

p94 belongs to the calcium-dependent cysteine protease (calpain) family which has been detected from human to mold. In contrast to the conventional m- and mu-calpains which are expressed ubiquitously, expression of p94 predominates in skeletal muscle, and the mRNA for p94 is at least 10-times more abundant than mRNAs encoding in the m- and mu-types. The unique feature of p94 is that it undergoes rapid and exhaustive autolysis with a half-life of less than half an hour. To elucidate the nature of specific and abundant expression in skeletal muscle, and to proceed toward gene targeting p94, we have cloned and characterized mouse and rat genes for p94, and compared them with that of the human sequence. The sequence comparison among three mammalian species revealed several conserved regions including possible transcription factor binding sites. Furthermore, mouse and rat upstream regions of p94 are conserved over 3 kb suggesting that expression of p94 in skeletal muscle of both rodents is similarly regulated.

Animals↗
PubMed1995

Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A.

Limb-girdle muscular dystrophies (LGMDs) are a group of inherited diseases whose genetic etiology has yet to be elucidated. The autosomal recessive forms (LGMD2) constitute a genetically heterogeneous group with LGMD2A mapping to chromosome 15q15.1-q21.1. The gene encoding the muscle-specific calcium-activated neutral protease 3 (CANP3) large subunit is located in this region. This cysteine protease belongs to the family of intracellular calpains. Fifteen nonsense, splice site, frameshift, or missense calpain mutations cosegregate with the disease in LGMD2A families, six of which were found within La Réunion island patients. A digenic inheritance model is proposed to account for the unexpected presence of multiple independent mutations in this small inbred population. Finally, these results demonstrate an enzymatic rather than a structural protein defect causing a muscular dystrophy, a defect that may have regulatory consequences, perhaps in signal transduction.

Amino Acid Sequence↗
PubMed1995

Beta-sarcoglycan: characterization and role in limb-girdle muscular dystrophy linked to 4q12.

beta-Sarcoglycan, a 43 kDa dystrophin-associated glycoprotein, is an integral component of the dystrophin-glycoprotein complex. We have cloned human beta-sarcoglycan cDNA and mapped the beta-sarcoglycan gene to chromosome 4q12. Pericentromeric markers and an intragenic polymorphic CA repeat cosegregated perfectly with autosomal recessive limb-girdle muscular dystrophy in several Amish families. A Thr-to-Arg missense mutation was identified within the beta-sarcoglycan gene that leads to a dramatically reduced expression of beta-sarcoglycan in the sarcolemma and a concomitant loss of adhalin and 35 DAG, which may represent a disruption of a functional subcomplex within the dystrophin-glycoprotein complex. Thus, the beta-sarcoglycan gene is the fifth locus identified (LGMD2E) that is involved in autosomal recessive limb-girdle muscular dystrophy.

Amino Acid Sequence↗
PubMed1995

Clean intermittent catheterisation from the acute period in spinal cord injury patients. Long term evaluation of urethral and genital tolerance.

Since its introduction by Lapides, clean intermittent catheterisation (CIC) has dramatically changed the urological management of spinal cord injury (SCI) patients. Since 1978 we have used CIC as a mode of drainage in the acute period, during the period of bladder retraining as a measurement of residual urine, and in some instances in the medium and long term. 12-14 Fr PVC catheters are used with lubricant. The objectives of this study were: first, in a population of 159 SCI patients (group 1), to evaluate the overall incidence of complications of CIC; Secondly to study two groups of patients: group 2 (n = 8) consisted of patients who had performed CIC for over 2 years before discontinuance; group 3 (n = 21) consisted of patients on CIC for over 5 years (mean length of use: 9.5 years). The reasons for acceptance of long term CIC, frequency of urinary tract infections, and rates of urethral strictures were evaluated. The analysis of group 1 showed a rate of lower urinary tract infection of 28% and of cytobacteriological infection of 60%. Chronic pyelonephritis was never observed and infection was always confined to the lower urinary tract which is in accordance with other studies. The rate of epididymitis and urethral stricture was 10% and 5.3% respectively. Sixty two per cent of group 2 remained incontinent, and 89% of group 3 showed a satisfactory degree of continence. The first factor for acceptance of long term CIC is continence, the second one is the ability to perform CIC independently. In group 3 we found a rate of urethral stricture of 19%, and of epidydimitis of 28.5%. These two complications (urethral tolerance and urethroprostatic infection) increased with the number of years on CIC. The method and the type of catheters used must also be considered. We need further studies of long term CIC in patients using non-reusable hydrophilic catheters from the acute period to see if these two complications can be prevented.

Acute Disease↗
PubMed1995

Persistence of distal motor control in the locked in syndrome. Review of 11 patients.

We report 11 patients with the locked in syndrome (LIS). The functional outcome was good in four patients with notable motor recovery, but motor deficit remained seriously disturbed in seven patients. All of the patients regained some distal control of finger and toe movements, often allowing functional use of a digital switch. The independence thereby gained is worthwhile, in some patients allowing environment control, communication by means of a computer, and electric wheelchair ambulation. When motor recovery occurs, the progression is disto-proximal with dramatic axial hypotonia. In five patients clinical insomnia was noted and polysomnography showed a reduction of REM sleep. The implications of systems other than the pyramidal tracts in the physiopathology of LIS are discussed.

Adolescent↗
PubMed1995

Genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy in a genetic isolate (Amish) and evidence for a new locus.

Limb-girdle muscular dystrophy (LGMD) is a hereditary myopathy presenting clinical and genetic heterogeneity. In 1991, a recessive form (LGMD2A) was linked to chromosome 15q in a genetic isolate from the Isle of La Réunion. Confirmation of this localization was subsequently reported in Brazilian and northern Indiana Amish pedigrees. Here we report the exclusion of the LGMD2A locus in six Amish kindreds from southern Indiana that are related by multiple consanguineous links to the same northern Indiana families in which the involvement of the chromosome 15 locus was previously demonstrated. These findings indicate unexpected genetic heterogeneity of LGMD in an Indiana Amish isolate. Furthermore, genetic analyses also ruled out the possible involvement of the chromosome 2 locus recently described (LGMD2B), thus demonstrating that a mutation within at least one additional locus leads to this condition. Several candidate genes putatively involved in neuromuscular disorders were also excluded.

Chromosomes, Human, Pair 15↗
PubMed1995

A primary expression map of the chromosome 15q15 region containing the recessive form of limb-girdle muscular dystrophy (LGMD2A) gene.

Previous genetic and physical studies of LGMD2A, an autosomal recessive form of limb-girdle muscular dystrophy, have led to the establishment of a 10-12 Mb YAC contig encompassing the morbid locus. In order to progress toward the identification of the gene involved in LGMD2A, a primary transcription map of this genomic region was generated. The direct cDNA selection strategy was used with three YACs covering the candidate region and two different muscle cDNA libraries. Seventeen transcription units were identified among 171 cDNA fragments analysed. Five sequences corresponded to known genes, and twelve to new ones. They were characterized for their sequences, physical positions within the YAC contig, and expression patterns. Among those specifically transcribed in muscle, the calpain gene is a good positional and functional candidate for LGMD2A.

Adult↗
PubMed1995

Preferential localization of the limb-girdle muscular dystrophy type 2A gene in the proximal part of a 1-cM 15q15.1-q15.3 interval.

A gene for a recessive form of limb-girdle muscular dystrophy (LGMD2A) has been localized to chromosome 15. A physical map of the 7-cM candidate 15q15.1-q21.1 region has been constructed by means of a 10-12-Mb continuum of overlapping YAC clones. New microsatellite markers developed from these YACs were genotyped on large, consanguineous LGMD2A pedigrees from different origins. The identification of recombination events in these families allowed the restriction of the LGMD2A region to an estimated 1-cM interval, equivalent to approximately 3-4 Mb. Linkage disequilibrium data on genetic isolates from the island of Réunion and from the Amish community suggest a preferential location of the LGMD2A gene in the proximal part of this region. Analysis of the interrelated pedigrees from Réunion revealed the existence of at least six different carrier haplotypes. This allelic heterogeneity is incompatible with the presumed existence of a founder effect and suggests that multiple LGMD2A mutations may segregate in this population.

Base Sequence↗
PubMed1994

Targeted development of microsatellite markers from inter-Alu amplification of YAC clones.

Primary genetic maps based on highly informative markers are now available. The local density of these markers may, however, not be sufficient. There is thus a need for new means to generate polymorphic markers from targeted regions of the genome. This can be achieved by selectively cloning and sequencing (CA)n-positive human inter-Alu sequences from targeted YAC clones. This method was tested on 21 YACs and led to the development of seven new polymorphic microsatellite markers.

Base Sequence↗
PubMed1994

Regional localization of human chromosome 15 loci.

One hundred forty-nine chromosome 15 loci were mapped by PCR with respect to chromosome breakpoints in three somatic cell hybrids retaining total or part of chromosome 15 and to a 10-Mb YAC contig. This chromosome was subdivided into 5 regions, yielding an average resolution of more than 1 sequence tagged site per megabase. The mapped loci included 18 genes, 60 cDNA-derived sequence tagged sites, and 69 microsatellites. In addition, the amount of chromosome 15 retained in line A15.1 has been defined. This work represents the first attempt at an integration of the human physical, expression, and genetic maps of chromosome 15.

Alleles↗
PubMed1994

Mapping of a chromosome 15 region involved in limb girdle muscular dystrophy.

A gene responsible for an autosomal recessive form of limb girdle muscular dystrophy (LGMD2, MIM number 253600) has been localized on chromosome 15. After genotyping additional markers of this chromosome, two were found to flank the disease locus within an interval that was assessed as 7 centiMorgans. The screening of the CEPH YAC libraries with the corresponding probes allowed the isolation of YACs which were used in fluorescence in situ hybridization to define the LGMD2 cytogenetic interval as 15q15.1-15q21.1. Four different approaches were pursued for the establishment of the physical map of this area which allowed the assembly of an uninterrupted YAC contig spanning an estimated 10-12 megabases, with an average STS resolution of 140 kb or for the 25 polymorphic microsatellites on this map, of 400 kb. Twelve genes and 25 genetic markers were positioned in this contig, which is constituted of a minimum of 10 clones.

Chromosome Mapping↗