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Biomedical subjects

D Raymond

Publications and source records attributed to D Raymond.

At least 19 recordsLinked to original sources
PubMed2000

A major locus for myoclonus-dystonia maps to chromosome 7q in eight families.

Myoclonus-dystonia (M-D) is an autosomal dominant disorder characterized by myoclonic and dystonic muscle contractions that are often responsive to alcohol. The dopamine D2 receptor gene (DRD2) on chromosome 11q has been implicated in one family with this syndrome, and linkage to a 28-cM region on 7q has been reported in another. We performed genetic studies, using eight additional families with M-D, to assess these two loci. No evidence for linkage was found for 11q markers. However, all eight of these families showed linkage to chromosome 7 markers, with a combined multipoint LOD score of 11.71. Recombination events in the families define the disease gene within a 14-cM interval flanked by D7S2212 and D7S821. These data provide evidence for a major locus for M-D on chromosome 7q21.

Chromosome Mapping↗
PubMed2000

The DYT1 phenotype and guidelines for diagnostic testing.

OBJECTIVE: To develop diagnostic testing guidelines for the DYT1 GAG deletion in the Ashkenazi Jewish (AJ) and non-Jewish (NJ) primary torsion dystonia (PTD) populations and to determine the range of dystonic features in affected DYT1 deletion carriers. METHODS: The authors screened 267 individuals with PTD; 170 were clinically ascertained for diagnosis and treatment, 87 were affected family members ascertained for genetic studies, and 10 were clinically and genetically ascertained and included in both groups. We used published primers and PCR amplification across the critical DYT1 region to determine GAG deletion status. Features of dystonia in clinically ascertained (affected) DYT1 GAG deletion carriers and noncarriers were compared to determine a classification scheme that optimized prediction of carriers. The authors assessed the range of clinical features in the genetically ascertained (affected) DYT1 deletion carriers and tested for differences between AJ and NJ patients. RESULTS: The optimal algorithm for classification of clinically ascertained carriers was disease onset before age 24 years in a limb (misclassification, 16.5%; sensitivity, 95%; specificity, 80%). Although application of this classification scheme provided good separation in the AJ group (sensitivity, 96%; specificity, 88%), as well as in the group overall, it was less specific in discriminating NJ carriers from noncarriers (sensitivity, 94%; specificity, 69%). Using age 26 years as the cut-off and any site at onset gave a sensitivity of 100%, but specificity decreased to 54% (63% in AJ and 43% in NJ). Among genetically ascertained carriers, onset up to age 44 years occurred, although the great majority displayed early limb onset. There were no significant differences between AJ and NJ genetically ascertained carriers, except that a higher proportion of NJ carriers had onset in a leg, rather than an arm, and widespread disease. CONCLUSIONS: Diagnostic DYT1 testing in conjunction with genetic counseling is recommended for patients with PTD with onset before age 26 years, as this single criterion detected 100% of clinically ascertained carriers, with specificities of 43% to 63%. Testing patients with onset after age 26 years also may be warranted in those having an affected relative with early onset, as the only carriers we observed with onset at age 26 or later were genetically ascertained relatives of individuals whose symptoms started before age 26 years.

Adolescent↗
PubMed2000

Leukocytosis in children with Escherichia coli O157:H7 enteritis developing the hemolytic-uremic syndrome.

BACKGROUND: Fewer than 10% of children with Escherichia coli O157:H7 enteritis develop hemolytic-uremic syndrome (HUS). OBJECTIVE: To determine whether circulating leukocytes are independent risk markers of developing HUS during E. coli O157:H7 enteritis. METHODS: We reviewed the charts of all children with culture-proved E. coli O157:H7 infections seen at Sainte-Justine Hospital between 1987 and 1997. Epidemiologic data, laboratory indices and circulating leukocytes counts were noted. HUS diagnosis was validated with independent HUS patient lists from the pediatric nephrology services of tertiary care hospitals in the Montreal metropolitan area. The date of onset of enteritis was determined by two independent observers. Leukocyte counts were compared among the following independent groups: (1) uncomplicated O157:H7 enteritis (Group 1); (2) O157:H7 enteritis with the subsequent development of HUS (Group 2); (3) HUS already present at the time of medical consultation (Group 3). RESULTS: There were 369 children with E. coli O157:H7 infection. A complete blood count was not performed in 114 (31%) patients. Observers disagreed on the date of onset of gastroenteritis in 34 (9%) children only (kappa 0.92). The study population thus included 221 patients: Group 1, n = 161; Group 2, n = 27; and Group 3, n = 33. Patients developing HUS (Group 2) presented greater total leukocyte (P < 0.008), polymorphonuclear (P < 0.008) and monocyte (P < 0.07) counts than those with an uncomplicated course (Group 1). Logistic regression analysis showed that young age [odds ratio (OR), 0.98; 95% confidence interval (CI), 0.96 to 0.99], duration of enteric prodrome < or =3 days (OR 4.8, 95% CI 1.13 to 20.7) and initial leukocytosis (OR 1.22, 95% CI, 1.11 to 1.35) were independent predictors of HUS. CONCLUSIONS: Based on the variables identified above, further studies are needed to determine whether the inflammatory response of the host represents only a marker of the severity of gastrointestinal infection or whether, alternatively, it is a pathophysiologic factor that leads to HUS.

Biomarkers↗
PubMed2000

Evaluation of the role of the D2 dopamine receptor in myoclonus dystonia.

A novel Val154-->Ile mutation in the D2 dopamine receptor (DRD2) on chromosome 11q23 has recently been shown to be associated with myoclonus dystonia (M-D) in one large family. Sequence analysis of the DRD2 gene in 5 M-D patients from different families did not reveal any mutations, nor was there evidence of linkage to the 11q23 region in the DRD2 gene in four other families. Receptor binding and signal transduction assays of the DRD2 mutant and wild-type receptors revealed identical agonist and antagonist affinities and functional responses. These studies suggest that M-D is genetically heterogeneous. The molecular mechanisms through which the Val-->Ile mutation may contribute to M-D remain to be determined.

Adolescent↗
PubMed1999

Localization of a gene for myoclonus-dystonia to chromosome 7q21-q31.

Essential myoclonus-dystonia is a neurological condition characterized by myoclonic and dystonic muscle contractions and the absence of other neurological signs or laboratory abnormalities; it is often responsive to alcohol. The disorder may be familial with apparent autosomal dominant inheritance. We report a large kindred with essential familial myoclonus-dystonia and map a locus for the disorder to a 28-cM region of chromosome 7q21-q31.

Adolescent↗
PubMed1998

Predicting readmission to hospital with asthma.

OBJECTIVES: To determine whether readmission to hospital for children aged 1-7 years with asthma can be predicted; and to discover whether factors related to the severity of the attack and past pattern of asthma, assessment of the parents' intention to treat the child with inhaled therapy, perceived consequences of treatment, habits of treatment and self-efficacy show a difference between those children subsequently readmitted and those who were not. METHODS: A specifically developed questionnaire was administered to parents of 121 children admitted with asthma. Clinical assessment was made of severity of the acute attack and past pattern of the asthma. One year after admission subjects were reviewed to determine those who had been readmitted. RESULTS: On univariate analysis, the negative perceived consequences of treatment with inhaled therapy were associated with an increased risk of readmission over a one-year period (P = 0.04). After adjusting for confounders (place of birth of mother, two- or one-parent family) and the effect-modifier of past pattern of the asthma (infrequent episodic, frequent episodic, persistent), the greater the negative perceived consequences of treatment, the more likely there would be readmission in children with infrequent episodic asthma. After adjusting for potential confounders, using logistic regression a decrease of one standard deviation in the negative perceived consequences score resulted in a one-third decrease in the odds of readmission (odds ratio (OR) = 0.31, 95% CI 0.12-0.83). CONCLUSIONS: Parents whose children are readmitted see greater negative perceived consequences of treatment. If asthma is infrequent episodic, the negative perceived consequences may be an inhibitor of treatment, whereas for more severe past patterns of asthma the severity is the controller of treatment. If parental negative consequences could be decreased, admissions for asthma may decrease.

Asthma↗
PubMed1997

Idiopathic torsion dystonia linked to chromosome 8 in two Mennonite families.

The DYT1 locus on chromosome 9q34 is responsible for most childhood limb-onset idiopathic torsion dystonia (ITD). Linkage to DYT1 has been excluded in families with adult-onset, and predominantly cranial-cervical, ITD. We mapped a locus (DYT6) associated with prominent cranial-cervical ITD in two large Mennonite families to chromosome 8. An identical haplotype spanning 40-cM segregates with ITD in these families, suggesting a shared mutation from the recent past.

Adolescent↗
PubMed1997

The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein.

Early-onset torsion dystonia is a movement disorder, characterized by twisting muscle contractures, that begins in childhood. Symptoms are believed to result from altered neuronal communication in the basal ganglia. This study identifies the DYT1 gene on human chromosome 9q34 as being responsible for this dominant disease. Almost all cases of early-onset dystonia have a unique 3-bp deletion that appears to have arisen idependently in different ethnic populations. This deletion results in loss of one of a pair of glutamic-acid residues in a conserved region of a novel ATP-binding protein, termed torsinA. This protein has homologues in nematode, rat, mouse and humans, with some resemblance to the family of heat-shock proteins and Clp proteases.

ATP-Binding Cassette Transporters↗
PubMed1997

Secondary dystonia and the DYTI gene.

Early-onset (< 28 years) primary dystonia in most Ashkenazi Jews is due to a single founder mutation in the DYT1 gene on chromosome 9q34, as determined by very strong linkage disequilibrium with a haplotype of 9q34 alleles at surrounding marker loci. The role of this mutation in individuals with secondary causes for dystonia has never been tested, although environmental insults, such as neuroleptic exposure or perinatal asphyxia, are proposed to precipitate dystonia in genetically predisposed individuals. We assessed 9q34 haplotypes in 40 Ashkenazi patients with secondary dystonia; 25 had early onset of symptoms, including 15 with exposure to neuroleptic medication or perinatal asphyxia. Of the 25 patients with early onset, 9 were considered phenocopies of DYT1 having normal examinations except for dystonia, normal radiographic and other laboratory studies, and onset in a limb or the neck. Only one individual whose dystonia developed in the setting of a measles infection carried the associated haplotype. Our findings indicate that clinical diagnostic criteria that include historical information to detect tardive dystonia and perinatal asphyxia discriminate primary dystonia due to the DYT1 founder mutation. We found no evidence that the DYT1 founder mutation contributes to secondary dystonia.

Adolescent↗
PubMed1996

Exclusion of the DYT1 locus in familial torticollis.

Clinical-genetic studies of idiopathic torsion dystonia (ITD) indicate that the DYT1 gene on chromosome 9q34 is responsible for most childhood limb-onset disease. The genetic basis of adult-onset ITD is less well studied. In most multiplex adult-onset ITD families, dystonia is limited to the cervical, cranial, or brachial muscles; in a few rare families, dystonia also involves the legs and trunk. Previous linkage studies have excluded the DYT1 locus in these atypical families. We studied two large non-Jewish families with adult-onset ITD limited to the cervical and brachial muscles and excluded the DYT1-containing region. This study further restricts the role of DYT1 to childhood limb-onset ITD and suggests that other genes are responsible for focal adult-onset ITD.

Adolescent↗
PubMed1996

Cognitive and psychodynamic correlates of depressive symptomatology.

31 depressed, 26 nondepressed participants completed measures reflecting putative cognitive and psychodynamic characteristics of self-reported depression. Of the 16 variables 9 discriminated the groups in the expected direction. Ten characteristics correlated significantly with scores on the Beck Depression Inventory, 4 reflecting negative automatic thinking, two of which (Negative Self-concepts and Expectations, Low Self-esteem) were important predictors of severity of depression.

Adult↗
PubMed1993

Improved PCR/NcoI method for the molecular diagnosis of medium chain acyl-CoA dehydrogenase deficiency using dried blood samples: two-stage amplification using two different sets of primers improves accuracy and sensitivity.

A 985A-->G transition is the single prevalent mutation representing 89% of all variant medium-chain acyl-CoA dehydrogenase (MCAD) alleles that causes MCAD deficiency. We and others previously devised a molecular method for the detection of the 985G allele that involves PCR coupled with NcoI digestion. The method has been widely used. However, when used for the analysis of dried blood samples, it sometimes produced ambiguous results with weak target bands in the presence of numerous artifact bands. An improved version of the method has been developed here, involving two stages of amplification using two different sets of primers. In the first stage, the entire exon-11 was amplified. A small aliquot (5 microliters) of the first PCR products were directly used as a template for the second PCR amplification. The second PCR is similar to the original method, but utilizes a pair of primers encompassing a smaller section within exon-11. The upstream primer incorporates a substitution at 981, so that a NcoI site involving 985G is introduced in the copies of the variant allele, as in the original PCR/NcoI method. The improved 2-stage method produces an intense target band with a very high sensitivity, yet devoid of artifacts, providing clean, unequivocal results.

Acyl-CoA Dehydrogenase↗