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Biomedical subjects

E W Chow

Publications and source records attributed to E W Chow.

8 recordsLinked to original sources
PubMed1999

Phenotype of adults with the 22q11 deletion syndrome: A review.

22q11 deletion syndrome (22qDS) is due to microdeletions of chromosome region 22q11.2. Little is known about the phenotype of adults. We reviewed available case reports of adults (age >/=18 years) with 22qDS and compared the prevalence of key findings to those reported in a large European survey of 22qDS (497 children and 61 adults) [Ryan et al., 1997: J. Med. Genet. 34:798-804]. Fifty-five studies reported on 126 adults (83 women, 40 men, 3 unknown sex), mean age 29.6 years (SD = 8.7 years). Compared with the European survey, adults with 22qDS reviewed had a lower rate of CHD, 30% versus 75%; chi(2) = 88.65, df = 1, P < 0.0001, but higher rates of identified palate anomalies, 88% versus 15%; chi(2) = 37.45, df = 1, P < 0.0001, and learning difficulties, 94% versus 79%; chi(2) = 12.13, df = 1, P = < 0.0008. The most common finding reported was minor facial anomalies. Few reports provided details of minor physical anomalies. Psychiatric conditions were more prevalent, 36% versus 18%; chi(2)= 5.71, df = 1, P < 0.02, than in the survey: 60% of reviewed adults were transmitting parents (72% mothers) ascertained following diagnosis of affected offspring. They had lower rates of CHD, cleft palate, and psychiatric disorders but similar rates of learning disabilities, and other palate and facial anomalies compared with adults ascertained by other methods. The results suggest that learning disabilities and facial and palate anomalies may be key findings in 22qDS adults, but that ascertainment is a key factor in the observed phenotype. Comprehensive studies of adults with 22qDS identified independently of familial transmission are necessary to further delineate the phenotype of adults and to determine the natural history of the syndrome.

Abnormalities, Multiple↗
PubMed1999

Linkage of familial schizophrenia to chromosome 13q32.

Over the past 4 years, a number of investigators have reported findings suggestive of linkage to schizophrenia, with markers on chromosomes 13q32 and 8p21, with one recent study by Blouin et al. reporting significant linkage to these regions. As part of an ongoing genome scan, we evaluated microsatellite markers spanning chromosomes 8 and 13, for linkage to schizophrenia, in 21 extended Canadian families. Families were analyzed under autosomal dominant and recessive models, with broad and narrow definitions of schizophrenia. All models produced positive LOD scores with markers on 13q, with higher scores under the recessive models. The maximum three-point LOD scores were obtained under the recessive-broad model: 3.92 at recombination fraction (theta).1 with D13S793, under homogeneity, and 4.42 with alpha=.65 and straight theta=0 with D13S793, under heterogeneity. Positive LOD scores were also obtained, under all models, for markers on 8p. Although a maximum two-point LOD score of 3.49 was obtained under the dominant-narrow model with D8S136 at straight theta=0.1, multipoint analysis with closely flanking markers reduced the maximum LOD score in this region to 2. 13. These results provide independent significant evidence of linkage of a schizophrenia-susceptibility locus to markers on 13q32 and support the presence of a second susceptibility locus on 8p21.

Canada↗
PubMed1998

22q11 deletion syndrome in adults with schizophrenia.

Genetic syndromes associated with deletions at chromosome 22q11 generally have been diagnosed during childhood based on a constellation of physical features. To investigate a reported association of velocardiofacial syndrome with psychotic disorders in adults, we assessed subjects with DSM-IV schizophrenia or schizoaffective disorder who were referred with two or more syndromal features (palatal, cardiac, facial, or other congenital anomalies, and/or learning difficulties). We report on 10 subjects (5 men and 5 women), mean age 27.2 (SD 6.0) years, who were found to have a 22q11 deletion at locus D22S75 using fluorescence in-situ hybridization (FISH). The mean age at onset of psychosis was 19.6 (SD 4.6) years. Symptoms and course of the psychotic illnesses were unremarkable, but additional signs such as temper outbursts were common. These adult subjects had significantly fewer major palatal (P = .0001) and conotruncal cardiac (P = .05) anomalies but the same high rate of learning difficulties as a sample with deletion 22q11 ascertained through a pediatric clinic [Lindsay et al. (1995): Am J Med Genet 57:514-522]. Minor congenital features and rate of transmitted cases were similar to those previously reported. These results replicate the association of a 22q11 deletion syndrome with schizophrenia and confirm the importance of ascertainment in influencing the phenotype found. The findings support a developmental gene in the 22q11 deletion region causing a complex phenotype which may include significant behavioral components that emerge over time. We support using the term "22q11 deletion syndrome (22DS)," which would encompass physical and psychiatric features, and could also be applied to describe a genetic subtype of schizophrenia.

Abnormalities, Multiple↗
PubMed1997

Use of a quantitative trait to map a locus associated with severity of positive symptoms in familial schizophrenia to chromosome 6p.

A number of recent linkage studies have suggested the presence of a schizophrenia susceptibility locus on chromosome 6p. We evaluated 28 genetic markers, spanning chromosome 6, for linkage to schizophrenia in 10 moderately large Canadian families of Celtic ancestry. Parametric analyses of these families under autosomal dominant and recessive models, using broad and narrow definitions of schizophrenia, produced no significant evidence for linkage. A sib-pair analysis using categorical disease definitions also failed to produce significant evidence for linkage. We then conducted a separate sibpair analysis using scores on positive-symptom (psychotic), negative-symptom (deficit), and general psychopathology-symptom scales as quantitative traits. With the positive symptom-scale scores, the marker D6S1960 produced P = 1.2 x 10(-5) under two-point and P = 5.4 x 10(-6) under multipoint analyses. Using simulation studies, we determined that these nominal P values correspond to empirical P values of .034 and .0085, respectively. These results suggest that a schizophrenia susceptibility locus on chromosome 6p may be related to the severity of psychotic symptoms. Assessment of behavioral quantitative traits may provide increased power over categorical phenotype assignment for detection of linkage in complex psychiatric disorders.

Canada↗
PubMed1995

Clinical use of clozapine in a major urban setting: one year experience.

This paper examines the clinical and demographic data of patients in the Clozapine Distribution System in Metropolitan Toronto in the first year after its inception. One hundred and thirty-seven patients were approved for funding during the year. They tended to be young, chronically and markedly ill patients suffering from schizophrenia, primarily with treatment resistance as the reason for clozapine therapy. Only 55 patients completed at least six months of therapy; 15 patients discontinued clozapine before six months of treatment, mainly because of side-effects and/or patients' noncompliance with bloodwork. Three patients discontinued clozapine because of haematological compromise. Clozapine was efficacious for the majority of patients who took it for at least six months, with improvement in all six clinical dimensions examined in the study. Nevertheless, the number of early discontinuation patients significantly lowered the overall effectiveness of clozapine in actual clinical practice.

Adolescent↗
PubMed1994

Velo-cardio-facial syndrome and psychotic disorders: implications for psychiatric genetics.

Psychiatric disorders have been reported in over 10% of patients with velo-cardio-facial syndrome (VCFS) in long-term follow-up. To further explore the behavioral and psychiatric findings associated with VCFS in adulthood, detailed clinical histories of two patients--one with VCFS who developed a psychotic illness, and one with schizophrenia who was found to have dysmorphological features associated with VCFS--are described in the current report. The observed overlap of physical and psychiatric symptoms in these two patients suggests that VCFS and psychotic disorders may share a pathogenetic mechanism. This could be consistent with a contiguous gene model for VCFS and psychosis, suggesting chromosome 22q11 as a possible candidate region for genetic studies of schizophrenia.

Abnormalities, Multiple↗
PubMed1982

Effect of 4-dimethylaminomethyl-1-(3-hydroxyphenyl)-1-nonen-3-one hydrochloride and related compounds on respiration in rat liver mitochondria.

4-Dimethylaminomethyl-1-(3-hydroxyphenyl)-1-nonen 3-one hydrochloride (II) was shown to stimulate respiration in rat liver mitochondria at levels of 2.5 mumoles or less; but at levels higher than 5.0 mumoles, respiration was inhibited when succinate and 3-hydroxybutyrate were the substrates. Compound II caused inhibition of respiration in the presence of glutamate over the dose range studied. The stimulating effect of II was attributed to its functioning as an uncoupling agent. Its inhibiting properties were considered to be due to its behaving like antimycin A in blocking transport of electrons between cytochromes b and c1. The effect of II on respiration in mitochondria varied with the pH of the medium. A conjugated styryl ketone, which contained a nuclear hydroxy function and was structurally related to II, also stimulated respiration at low doses while inhibiting respiration at higher concentrations. Etherification of the hydroxy group led to compounds in which only stimulation of respiration was noted.

2,4-Dinitrophenol↗