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J Demaille

Publications and source records attributed to J Demaille.

At least 55 records · Page 3Linked to original sources
PubMed1998

Familial Mediterranean fever clinical and genetic features in Druzes and in Iraqi Jews: a preliminary study.

OBJECTIVE: A number of differences have been noted in clinical familial Mediterranean fever (FMF) among ethnic groups. Iraqi Jews and Druzes are characterized by less severe disease. The differences in disease expression raise the possibility of background genes peculiar to specific ethnic groups. METHODS: We analyzed a series of FMF linked microsatellite markers and searched for gene mutations in these 2 populations. RESULTS: We observed a conserved haplotype in 46% of the FMF druze chromosomes that was different from the Mediterranean haplotype but identical to the ARM3 haplotype. In contrast, 56% of the FMF chromosomes in Iraqi Jews displayed the same mutation as that found in Jews from North Africa. CONCLUSION: Variable expression in FMF is probably due to both allelic heterogeneity and/or modifier genes as well as environmental factors.

Adolescent↗
PubMed1997

The protein truncation test (PTT) as a method of detection for choroideremia mutations.

The predominance of truncative mutations responsible for choroideremia (CHM) led us to investigate the use of the protein truncation test (PTT) applied to lymphocyte RNA derived from affected males as a scanning method. The entire CHM coding region was reversed-transcribed in three overlapping cDNA segments (RT-PCR) which were amplified and further analysed by PTT after in vitro transcription/ translation. This strategy enabled us to detect the CHM-causative alteration in each of the four unrelated patients from southern France who were investigated. We describe three novel mutations (E177X, 323delT, 1313delTC), and report one recurrent mutation (R267X) in CHM. We believe this to be the first attempt at applying RT-PCR-PTT to CHM mutation detection.

Choroideremia↗
PubMed1997

Cystic fibrosis in Lebanon: distribution of CFTR mutations among Arab communities.

Cystic fibrosis (CF) is thought to be rare among the Arab populations from the Middle East and little data have been reported so far. We have studied a sample of 20 families living in Lebanon for several generations and who have at least one child with CF. These families are mainly from the Maronite, Greek Catholic, Greek Orthodox. Shiite or Sunnite groups. We found a 50% rate of consanguineous marriage, independent of the community of origin. The distribution of CF genotypes was determined through the screening of all exons of the CFTR (cystic fibrosis transmembrane conductance regulator) gene by the technique of denaturing gradient gel electrophoresis combined with asymmetric amplification DNA sequencing. A total of ten different mutations accounting for 87.5% of 32 unrelated CF alleles was identified, including two novel putative mutations (E672del and IVS21-28G-->A). Three mutations, delta F508 (37.5%), W1282X (15.6%), and N1303K (9.4%) accounted for 62.5% of CF alleles. Interestingly, in the Maronite group, 66.7% of the delta F508 chromosomes were found to be associated with allele 7 of the IVS8(T)tract, contrasting with the absolute linkage disequilibrium between European delta F508 chromosomes and allele 9. During this study, two previously undescribed polymorphisms (IVS14a + 17del5 and 2691T/C) were also identified.

Arabs↗
PubMed1997

Recurrent PIG-A mutation (IVS5+1G-->A) in a paediatric case of paroxysmal nocturnal haemoglobinuria: detection by the protein truncation test.

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haemopoietic stem cell disorder caused by the absence of glycosyl phosphatidylinositol (GPI)-anchored surface proteins due to a deficient biosynthesis of GPI-anchor. The disease occurs predominantly in adults, and very few cases have been described in children and adolescents. Recent analyses have shown that null mutations in the X-linked PIG-A (phosphatidylinositol glycan-class A) gene are responsible for GPI-anchor deficiency in most PNH adult patients analysed. We report a young male from southern France who was diagnosed with PNH at 12 years of age during follow-up of aplastic anaemia. To further elucidate the molecular basis of PNH occurring in childhood, we used the powerful and rapid protein truncation test to scan for truncative mutations in the entire PIG-A mRNA reverse transcribed and amplified from blood mononuclear cells. The somatic defect responsible for PNH in the patient was found to be a splicing mutation. IVS5+1G-->A, which has previously been described in two Asiatic adults with PNH.

Child↗
PubMed1997

Genotypic diagnosis of familial Mediterranean fever (FMF) using new microsatellite markers: example of two extensive non-Ashkenazi Jewish pedigrees.

Familial Mediterranean fever is an autosomal recessive disease characterised by multiple attacks of serosal inflammation in the absence of treatment. In the absence of timely diagnosis, renal amyloidosis is a life threatening complication. The diagnosis is often missed because no specific test is available. Early colchicine treatment prevents attacks and renal complications. The FMF gene (MEF) has been mapped to chromosome 16p 13.3 but has not yet been identified. We compared the suitability of a series of microsatellite markers (four of them were new) and propose the routine use of seven of these markers, exhibiting alleles in strong linkage disequilibrium with the disease and informative in 100% of diagnosed patients. Moreover, the discovery of a homozygous status for the 3-3-9 (or 3-3-18) haplotype at the core loci (D16S3070, D16S3082, and D16S3275), which was found in 73% non-Ashkenazi Jewish patients, points to a diagnosis of FMF, even in sporadic cases, with a risk of error of only 2.10(-5). Two extensive pedigrees covering most indications for genetic counselling are presented, showing that it is now possible both prospectively and retrospectively to identify members likely to have MEF mutations. With the help of this accurate test, colchicine treatment can be better targeted, especially where the symptomatology is mild or atypical.

Chromosome Mapping↗
PubMed1997

A complex allele (1064delTC and IVS2 + 22ins7) in the peripherin/RDS gene in retinitis pigmentosa with macular dystrophy.

Because mutations in the peripherin/RDS gene have been found in retinal dystrophies involving the macula, we examined various types of macular dystrophies from southern France to characterize sequence variations that may be associated with these conditions. DNA sequence analysis of the full coding and flanking regions of the peripherin/RDS gene was performed in fifteen unrelated patients with different types of macular dystrophy, including nine with retinitis pigmentosa (RP). Of the 15 probands with macular disease, two (13.3%) were found to carry a mutation in the peripherin/RDS gene. The recurrent mutation P216S was identified in a pedigree with autosomal dominant RP. A previously unreported complex allele (1064delTC associated with IVS2 + 22ins7) that is predicted to result in the premature termination of peripherin/RDS synthesis was identified in a sporadic case of macular atrophy with RP. We also report eight novel neutral sequence variations in the peripherin/RDS gene, most of them found in the 3' untranslated part of the gene.

Adult↗
PubMed1997

An exonic polymorphism (381A/G) in the choroideremia gene.

By using the single strand conformational analysis (SSCA) to search for point mutations in the choroideremia gene, we have identified a previously undescribed polymorphism within exon 5a (381A/G). We have studied the frequency of this polymorphism in a population from Southern France. The sequence variation creates a new restriction site for HhaI, allowing a convenient DNA-based genetic counseling in families in which the causal disease mutation is unknown.

Choroideremia↗
PubMed1997

[Rapid genetic diagnosis of females carriers related to patients with choroideremia].

PURPOSE: By using the single strand conformation analysis to search for point mutations in the choroideremia gene, we had previously identified the first truncative mutation responsible for CHM in France. The aim of the present study was to perform a simple and nonisotopic routine test to identify carriers and non carriers in the relevant family. METHODS: We used a PCR-based restriction analysis to detect the presence or absence of the mutation in the family members, as the mutation creates a restriction site in the coding sequence of the CHM gene. RESULTS: We could follow the segregation of the mutation in the pedigree, and unambiguously determine the genetic status of the females. CONCLUSION: When a mutation responsible for choroideremia modifies a restriction site, the PCR-restriction provides an efficient and unexpensive one-day test to detect heterozygosity in the family.

Carrier State↗
PubMed1996

Transcript analysis of CFTR frameshift mutations in lymphocytes using the reverse transcription-polymerase chain reaction technique and the protein truncation test.

mRNA transcripts of the cystic fibrosis transmembrane conductance regulator (CFTR) gene were analyzed from lymphocytes of two cystic fibrosis compound heterozygotes (394delTT/3195del6 and 1215delG/ 2423delG), of five related carriers heterozygous for one of these mutations, and of five normal individuals. After reverse transcription of total RNA and amplification by the polymerase chain reaction, fragments were investigated by sequencing and by the protein truncation test (PTT). The three frameshift mutants were correctly detected by PTT, as they introduced a premature termination codon resulting in shortened protein products. The PTT approach thus provides a simple and reliable alternative method for detecting frameshift, nonsense, or splice site mutations, and for ascertaining their putative effect on the reading frame of the mRNA. In addition, we have identified 6 alternatively spliced forms of CFTR mRNA, two of which (transcripts lacking 4 + 5 or 17B) have not been described previously.

Adolescent↗
PubMed1996

Four novel dystrophin point mutations: detection by protein truncation test and transcript analysis in lymphocytes from Duchenne muscular dystrophy patients.

About 30% of cases of Duchenne muscular dystrophy (DMD) result from point mutations randomly distributed in the immense dystrophin gene. As already observed for the gross rearrangements, most of the DMD point mutations identified so far give rise to truncated proteins. Here, we report results of a comprehensive search for point mutations within the dystrophin gene based on illegitimate transcript analysis by using the RT-PCR technique in combination with a method capable of selectively detecting translation-termination mutations, called the protein truncation test (PTT). The RT-PCR-PTT procedure was successful in detecting mutations in 4 out of the 6 DMD patients who were investigated. These mutations, Q2972X in exon 59, 3474insC in exon 24, delT393-G394+5 in exon/intron 3, and 2436delAG in exon 18, had not been previously described. Moreover, several alternatively spliced forms of ectopic dystrophin mRNA were characterized in normal controls or in DMD patients. Most of these differentially spliced messages consisting of exon skipping or intronic sequence insertion are reported here for the first time.

Adult↗
PubMed1995

Heterotaxia syndrome and autosomal dominant inheritance.

Previous familial cases of recurrent heterotaxia have suggested an autosomal recessive or exceptionally X-linked or dominant inheritance. Here, we report six families including 18 affected members, consistent with autosomal dominant inheritance. Among these, four families have more than one case of heterotaxia. The other two families have one member with heterotaxia and at least one other affected member with an "isolated" heart malformation, which could be considered as a mild form of heterotaxia. In five families, the disorder is transmitted through two or three generations. In one family, the patients are of the same generation but are linked to each other by obligate carriers. We suggest a rule to classify these families with heart malformations, according to the etiologic factor involved (rule of precocity). This rule might be useful to other disruptions of morphogenetic processes.

Fatal Outcome↗
PubMed1995

Protein truncation test: analysis of two novel point mutations at the carboxy-terminus of the human dystrophin gene associated with mental retardation.

Approximately one-third of the mutations responsible for Duchenne muscular dytrophy (DMD) do not involve gross rearrangements of the dystrophin gene. Methods for intensive mutation screening have recently been applied to this immense gene, which resulted in the identification of a number of point mutations in DMD patients, mostly translation-terminating mutations. A number of data raised the possibility that the C-terminal region of dystrophin might be involved in some cases of mental retardation associated with DMD. Using single-strand conformation analysis of products amplified by polymerase chain reaction (PCR-SSCA) to screen the terminal domains of the dystrophin gene (exons 60-79) of 20 unrelated patients with DMD or BMD, we detected two novel point mutations in two mentally retarded DMD patients: a 1-bp deletion in exon 70 (10334delC) and a 5' splice donor site alteration in intron 69 (10294 + 1G-->T). Both mutations should result in a premature translation termination of dystrophin. The possible effects on the reading frame were analyzed by the study of reverse transcripts amplified from peripheral blood lymphocytes mRNA and by the protein truncation test.

Base Sequence↗
PubMed1995

Implications for cAMP-dependent protein kinase in the maintenance of the interphase state.

The cAMP dependent protein kinase (A-kinase) is one of the first and best studied kinases in mammalian cells. There is extensive evidence that A-kinase activity acts antagonistically toward mitotic entry both in oocyte and somatic cells. Firstly, A-kinase seems to directly compromise the activation process of the cdc2 cyclin B mitotic kinase. Secondly, as shown by specific in vivo inhibition of A-kinase using microinjection of a stable form of its inhibitor peptide PKI, A-kinase modulates several key interphase cellular processes including cytoskeletal dynamics, transcription, chromatin structure and nuclear localization. We discuss the potential mechanisms involved in the down regulation of A-kinase activity at the interphase/mitosis transition.

Animals↗
PubMed1995

Four adult patients with the missense mutation L206W and a mild cystic fibrosis phenotype.

We report molecular and clinical analyses in four unrelated patients with cystic fibrosis (CF) with compound heterozygosity for the L206W mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR). This uncommon missense mutation (frequency less than 1% in a sample of 336 CF chromosomes from Southern France) replaces a leucine by a tryptophan residue in the middle of the third transmembrane domain of CFTR. On the basis of the clinical features presented by the four patients, we postulate that the L206W might be associated with pancreatic sufficiency and residual transmembrane transport of chloride in lung.

Adolescent↗
PubMed1995

Identification of variable length polyadenosine tract at the dystrophin locus.

We report the characterization of a length polymorphism in the human dystrophin gene, consisting of single-base pair increments in a polyadenosine tract located near the 3' end of exon 68. Using Single Strand Conformation Analysis (SSCA), three length alleles could be identified (10,182 + 13A9/10/11). This class of 1-bp length variant is rare among known intronic gene sequences, and has been described only once in the dystrophin gene. Furthermore, the high polymorphic content (0.56) of this novel marker and its distal localization in the 3' end of the coding sequence make it suitable for diagnostic purposes.

Alleles↗
PubMed1995

Scanning gel densitometry of amniotic fluid acetylcholinesterase and butyrylcholinesterase: quantification of 'faint-positive' bands in fetal malformations.

The quantification of 'faint-positive' cholinesterases in amniotic fluid was performed in 40 patients with positive acetylcholinesterase (AchE) tests. Fetuses with anencephaly and open spina bifida presented an AchE/butyrylcholinesterase (A/B) ratio of more than 0.3 with clearly dense bands. Fetuses with gastroschisis showed a 'faint-positive' AchE band (A/B < 0.3). In 5 fetuses (1 teratoma, 3 open spina bifida, 1 unaffected) we found faint AchE and butyrylcholinesterase bands.

Acetylcholinesterase↗