Biomedical subjects

Catherine Dode

Publications and source records attributed to Catherine Dode.

3 recordsLinked to original sources

PubMed2004

Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16.

Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Delta2642 (within the HD coding sequence), and BJ56 ( D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Delta2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker.

Adolescent↗

PubMed2004

Infevers: an evolving mutation database for auto-inflammatory syndromes.

The Infevers database (http://fmf.igh.cnrs.fr/infevers/) was established in 2002 to provide investigators with access to a central source of information about all sequence variants associated with periodic fevers: Familial Mediterranean fever (FMF), TNF Receptor Associated Periodic Syndrome (TRAPS), Hyper IgD Syndrome (HIDS), Familial Cold Autoinflammatory Syndrome/Muckle-Wells Syndrome/Chronic Infantile Neurological Cutaneous and Articular Syndrome (FCAS/MWS/CINCA). The prototype of this group of disorders is FMF, a recessive disease characterized by recurrent bouts of unexplained inflammation. FMF is the pivotal member of an expanding family of autoinflammatory disorders, a new term coined to describe illnesses resulting from a defect of the innate immune response. Therefore, we decided to extend the Infevers database to genes connected with autoinflammatory diseases. We present here the biological content of the Infevers database, including the introduction of two new entries: Crohn/Blau and Pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA syndrome). Infevers has a range of query capabilities, allowing for simple or complex interrogation of the database. Currently, the database contains 291 sequence variants in related genes (MEFV, TNFRSF1A, MVK, CARD15, PSTPIP1, and CIAS1), consisting of published data and personal communications, which has revealed or refined the preferential mutational sites for each gene. This database will continue to evolve in its content and to improve in its presentation.

Arthritis↗

PubMed2003

Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes.

We report a group of 252 patients with a Huntington's disease-like (HDL) phenotype, including 60 with typical Huntington's disease, who had tested negative for pathological expansions in the IT15 gene, the major mutation in Huntington's disease. They were screened for repeat expansions in two other genes involved in HDL phenotypes: those encoding the junctophilin-3 (JPH3/HDL2) and prion (PRNP/HDL1) proteins. In addition, because of the clinical overlap between patients with HDL disease and autosomal dominant cerebellar ataxia or dentatorubral and pallidoluysian atrophy (DRPLA), we investigated trinucleotide repeat expansions in genes encoding the TATA-binding protein (TBP/SCA17) and atrophin-1 (DRPLA). Two patients carried 43 and 50 uninterrupted CTG repeats in the JPH3 gene. Two other patients had 44 and 46 CAA/CAG repeats in the TBP gene. Patients with expansions in the TBP or JPH3 genes had HDL phenotypes indistinguishable from Huntington's disease. Taking into account patients with typical Huntington's disease, their frequencies were evaluated as 3% each in our series of typical HDL patients. Interestingly, incomplete penetrance of the 46 CAA/CAG repeat in the TBP gene was observed in a 59-year-old transmitting, but healthy, parent. Furthermore, we report a new configuration of the expanded TBP allele, with 11 repeats on the first polymorphic stretch of CAGs. Expansions in the DRPLA gene and insertions in the PRNP gene were not found in our group of patients. Further genetic heterogeneity of the HDL phenotype therefore exists.

Adult↗