Search PubMed⌕ Search

Biomedical subjects

D Bonneau

Publications and source records attributed to D Bonneau.

At least 19 recordsLinked to original sources
PubMed1995

A gene for blepharophimosis-ptosis-epicanthus inversus syndrome maps to chromosome 3q23.

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal dominant malformation of the eyelids that may severely impair visual function. Chromosomal aberrations involving chromosomes 3q23, 3p25 and 7p34 have been reported in BPES but the disease gene has not been hitherto localized by linkage analysis. We have mapped a gene for BPES to chromosome 3q23 in a large French pedigree (Zmax = 4.62 at Theta = 0 for probe AFM 182yc5 at locus D3S1549). The best estimate for the location of the disease gene is at locus D3S1549, between the loci D3S1292 and D3S1555 (maximum lod score of 5.10).

Abnormalities, Multiple↗
PubMed1995

Exclusion of the cone-specific alpha-subunit of the transducin gene in Stargardt's disease.

Stargardt's disease is an autosomal recessive infantile macular degeneration of unknown origin whose gene has been recently mapped to chromosome 1p21-p13 by linkage analysis in eight multiplex families. Since the cone-specific alpha-subunit of the transducin gene (GNAT2) has been mapped to chromosome 1p13, we tested GNAT2 as the disease-causing gene in our series. Using a novel intragenic polymorphism, we show here that GNAT2 is most probably located centromeric to the genetic interval encompassing the disease gene (D1S424-D1S236, location score = 3.54). In addition, single-strand conformation polymorphism and sequence analyses of the eight exons of the GNAT2 gene was performed in our probands. No evidence of a deleterious base substitution was observed in any affected individual. Taken together, these results support the exclusion of GNAT2 as the causal disease gene of Stargardt's disease. come. The pathogenesis is unknown and the treatment is limited to ultraviolet ray protection with dark glasses. Stargardt's disease has been recently mapped to chromosome 1p21-p13 in the genetic interval defined by loci D1S424 and D1S236. In addition, our previous study has suggested that Stargardt's disease is genetically homogeneous (Kaplan et al. 1993). With respect to the physical mapping of the proteins specific to the retinal pigmentary epithelium or to cones we noted that the cone-specific alpha-subunit of the transducin gene (GNAT2) has been mapped to chromosome 1p13 (Wilkie et al. 1992). The human GNAT2 is 9967 bp in length and consists of eight exons with seven introns (Morris and Fong 1993). In the present study, we examined this gene as the candidate gene in eighteen unrelated patients affected with Stargardt's disease.

Base Sequence↗
PubMed1995

[Hyperexplexia].

Hyperexplexia is a disease of neonatal onset characterized by an exaggerated startle reflex. Early diagnosis is important to rule out epilepsy. Clinical findings are mainly hypertony and generalized startle reflex which is exaggerated by tiredness and some exogenous stimuli. Electroencephalogram is normal. The expression of the disease is variable including minor forms that may be unnoticed and major forms with arthrogryposis-like symptoms, orthopedic complications, false passages, apnea and even sudden infant death (SID). The evolution is generally benign and symptoms disappear within 2 or 3 years. A neuromotor retardation is often present, without intellectual deficit. In severe forms, the risk of SID requires a multidisciplinary follow-up including monitoring and treatment with clonazepam. A low GABA level in cerebrospinal fluid has been reported. Present etiological hypotheses include neuromediator and/or receptor dysfunction.

Humans↗
PubMed1995

Mutation in the iron responsive element of the L ferritin mRNA in a family with dominant hyperferritinaemia and cataract.

The synthesis of ferritin, the iron-storing molecule, is regulated at the translational level by iron through interaction between a cytoplasmic protein, iron regulatory protein (IRP), and a conserved nucleotide motif present in the 5' non-coding region of all ferritin mRNAs--the iron responsive element (IRE). This region forms a stem-loop structure and when the supply of iron to the cells is limited, the IRP is bound to IRE and represses ferritin synthesis. Ferritin is composed of a 24-subunit protein shell surrounding an iron core. The two types of subunit, H and L, are encoded by two genes located on chromosomes 11q13 and 19q13.1, respectively. Both genes are ubiquitously expressed but transcriptional regulation mediates tissue-specific changes in the H/L mRNA ratio and isoferritin profiles. We now report the identification of a single point mutation in the IRE of the L-ferritin mRNA in members from a family affected with dominantly inherited hyperferritinaemia and cataract. This mutation consists of an A to G change in the highly conserved CAGUGU motif that constitutes the IRE loop and mediates the high-affinity interaction with the IRP. We show that this mutation abolishes the binding of IRP in vitro and leads to a high constitutive, poorly regulated L-ferritin synthesis in cultured lymphoblastoid cells established from affected patients. This is, to our knowledge, the first mutation affecting the IRP-IRE interaction and the iron-mediated regulation of ferritin synthesis. We suggest that excess production of ferritin in tissues is responsible for the hyperferritinaemia and that intracellular accumulation of ferritin leads to cataract.

Base Sequence↗
PubMed1995

A gene for Leber's congenital amaurosis maps to chromosome 17p.

Leber's congenital amaurosis (LCA) is an autosomal recessive disease responsible for congenital blindness. It is the most early and severe form of inherited retinopathy and accounts for 5% of all inherited retinal dystrophies. Here we report the first mapping of a gene for LCA to the distal short arm of chromosome 17 by linkage analysis in 15 multiplex families (Zmax = 5.14 at theta = 0.15 for probe AFM070xg5 at the D17S1353 locus). When our sample was split into two groups according to the ethnic origin of the patients we were able to confirm the presence of a gene for LCA on chromosome 17p by both homozygosity mapping and linkage analysis in five families of Maghrebian origin (LCA1, Zmax = 7.21 at theta = 0.01 at the D17S1353 locus), while negative results were found in 10 families of French ancestry. Haplotype analyses supported the placement of LCA1 between loci D17S796 and D17S786 (maximum likelihood estimate for location of the disease gene over the D17S1353 locus). The genetic heterogeneity of LCA will complicate the prenatal detection of this frequent cause of congenital blindness.

Blindness↗
PubMed1995

[Choledochal cysts. A rare prenatal diagnosis].

Forty to sixty percent of main bile duct cysts are diagnosed before the age of 10 years, often at the time of a complication. Current progress in echography now makes it possible to diagnose such cysts antenatally. Wze report a case discovered at 33 gestation and focus on the difficulty of formal antenatal diagnosis and the unpredictable, sometimes rapid, course of the disease. The main prognosis factor is the development of complications, especially liver fibrosis. Antenatal suspicion of main bile duct cyst is important as they can then be managed early after echographic confirmation during the first days of life with the potential reduction in severe complications.

Adult↗
PubMed1995

A gene for late-onset fundus flavimaculatus with macular dystrophy maps to chromosome 1p13.

Fundus flavimaculatus with macular dystrophy is an autosomal recessive disease responsible for a progressive loss of visual acuity in adulthood, with pigmentary changes of the macula, perimacular flecks, and atrophy of the retinal pigmentary epithelium. Since this condition shares several clinical features with Stargardt disease, which has been mapped to chromosome 1p21-p13, we tested the disease for linkage to chromosome 1p. We report here the mapping of the disease locus to chromosome 1p13-p21, in the genetic interval defined by loci D1S435 and D1S415, in four multiplex families (maximum lod score 4.79 at recombination fraction 0 for probe AFM217zb2 at locus D1S435). Thus, despite differences in the age at onset, clinical course, and severity, fundus flavimaculatus with macular dystrophy and Stargardt disease are probably allelic disorders. This result supports the view that allelic mutations produce a continuum of macular dystrophies, with onset in early childhood to late adulthood.

Alleles↗
PubMed1994

Genetic heterogeneity of Usher syndrome type 1 in French families.

Usher syndrome type 1 (US1) is an autosomal recessive disease characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa, and constant vestibular dysfunction. Three localizations have been described in US1: USH1A, 14q32; USH1B, 11q13.5; and USH1C, 11p15. Studying a series of 33 affected individuals belonging to 20 US1 pedigrees of French ancestry, we found that none of the three localizations accounted for all US1 families in our series (Zmax = 1.48 at theta = 0.10; Zmax = 1.45 at theta = 0.10; and Zmax = 0.36 at theta = 0.20 for probes MLJ14, Zd5, and Mfd58, respectively, at loci D14S13, D11S527, and D11S419, respectively). However, when our sample was split into two groups according to the geographic origin of the probands' grandparents, we were able to confirm the presence of a gene for US1 on chromosome 14q32 (USH1A) in 9 families originating from the Poitou region in Western France (Department of Deux-Sèvres; Zmax = 4.46 at theta = 0 for probe MLJ14 at the D14S13 locus, Morton likelihood ratio test, P < 0.01). Moreover, we refined the genetic mapping of USH1A by showing that the disease gene maps to the D14S13 locus, within the genetic interval defined by loci D14S78 and D14S250 (location score in log base 10 = 4.90). Consistent with this, nonsignificant lod score values for linkage to either USH1B or USH1C were found in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromosomes, Human, Pair 11↗
PubMed1994

X-linked spastic paraplegia and Pelizaeus-Merzbacher disease are allelic disorders at the proteolipid protein locus.

Three forms of X-linked spastic paraplegia (SPG) have been defined. One locus (SPG 1) maps to Xq28 while two clinically distinct forms map to Xq22 (SPG2). A rare X-linked dysmyelinating disorder of the central nervous system, Pelizaeus-Merzbacher disease (PMD), has also been mapped to Xq21-q22, and is caused by mutations in the proteolipid protein gene (PLP) which encodes two myelin proteins, PLP and DM20. While narrowing the genetic interval containing SPG2 in a large pedigree, we found that PLP was the closest marker to the disease locus, implicating PLP as a possible candidate gene. We have found that a point mutation (His139Tyr) in exon 3B of an affected male produces a mutant PLP but a normal DM20, and segregates with the disease (Zmax = 6.63, theta = 0.00). It appears, therefore, that SPG2 and PMD are allelic disorders.

Alleles↗
PubMed1994

Abnormal methylation pattern in constitutive and facultative (X inactive chromosome) heterochromatin of ICF patients.

We have investigated the distribution of DNA methylation in chromosomes and nuclei of normal individuals and ICF (Immunodeficiency, Centromeric instability and Facial abnormalities) syndrome patients, using 5-methylcytosine monoclonal antibody. In this syndrome, DNA digestion with methyl-sensitive enzymes has previously shown a specific hypomethylation of classical satellites located in constitutive heterochromatin. The chromosome methylation pattern confirms this hypomethylation showing in addition a clear undermethylation of facultative heterochromatin (X inactive chromosome). Antibodies give, in normal and ICF chromosomes, a non-uniform labeling of euchromatin, generating a weak R-like banding pattern on chromosomes. This pattern reflects an unequal distribution of DNA methylation over the genome disclosing another aspect of chromosome organization. The breakpoints of chromosome rearrangements and the heterochromatin stretchings observed in ICF patients were analyzed by means of in situ hybridization. These chromosome modifications involve hypomethylated classical DNA satellite sequences. The underlying hypomethylation, associated with an abnormal chromatin organization, may predispose to chromosome instability.

5-Methylcytosine↗
PubMed1994

Possible involvement of a gamma-hydroxybutyric acid receptor in startle disease.

Startle disease or hyperreflexia is an autosomal dominant neurological disorder, with a neonatal onset, characterized by muscular hypertonia and myoclonic jerks, exaggerated by the slightest stimulus. Low concentrations of free gamma-aminobutyric acid (GABA) have been found in the cerebrospinal fluid of two affected infants. The involvement of GABA or its receptors has been raised and the use of GABA-agonist drugs has been suggested. We report a newborn with startle disease who also had a low concentration of GABA in the cerebrospinal fluid. No clinical improvement was observed with progabide, a GABA agonist. Furthermore, a high dose (100 mg/kg) of gamma-hydroxybutyrate (GHB) did not improve muscular stiffness and failed to induce general anesthesia. GHB, currently used as an effective general anaesthetic, is a structural analogue of GABA. It is present naturally at low concentrations in the brain and is regarded as an inhibitory neurotransmitter. Two specific GHB receptors, distinct from the GABA receptors, have been identified in rat brain. Failure to induce general anesthesia with a high dose of GHB suggests that one of these receptors could be involved in startle disease.

Anesthetics↗