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D E Comings

Publications and source records attributed to D E Comings.

At least 91 records · Page 5Linked to original sources
PubMed1993

The dopamine D2 receptor (DRD2) as a major gene in obesity and height.

Dopamine plays a major role in the regulation of appetite and growth hormone. Dopaminergic agonists suppress appetite and dopamine D2 receptor antagonists enhance it. We examined the hypothesis that allelic variants of the DRD2 locus may be associated with weight and height. Sarkar and Sommer described two DRD2 polymorphisms that could be haplotyped by PCR. For weight, the mean Z score (National Center for Health Statistics) for 208 subjects without haplotype 4 was 0.086 versus 0.557 for 280 subjects with haplotype 4, P = 0.0003. Two separate sets of subjects were studied and these results were significant for both, providing an internal replication. For height, the mean Z score for 164 subjects without haplotype 4 was 0.1677 versus 0.6885 for 219 subjects with haplotype 4, P < 0.00001. These and other data suggest that the 4 haplotype is in linkage disequilibrium with allelic variants of the DRD2 gene that play a major role in the regulation of weight (obesity) and height, and may serve as a risk factor in late-onset non-insulin-dependent diabetes mellitus (NIDDM).

Adolescent↗
PubMed1993

Serotonin and the biochemical genetics of alcoholism: lessons from studies of attention deficit hyperactivity disorder (ADHD) and Tourette syndrome.

Studies of children with ADHD and Tourette syndrome, and their families, show that both the patients and their relatives are at increased risk for alcoholism, and other behavioral disorders. Defective serotonin metabolism has been implicated in all of these disorders. Platelet serotonin and blood tryptophan levels are low in the patients and both parents. Analysis of pedigrees suggest that a gene or genes capable of producing a pleiotrophic spectrum of disorders are inherited from both parents (recessive inheritance), but affected relatives can express some symptoms (dominant inheritance). This suggests an intermediate semirecessive-semidominant inheritance of a common gene affecting serotonin metabolism for ADHD, Tourette syndrome, alcoholism and related disorders. Tryptophan 2,3 dioxygenase (TDO2) is suggested as a possible candidate gene.

Adult↗
PubMed1993

Tourette's syndrome and attention-deficit hyperactivity disorder: evidence for a genetic relationship.

BACKGROUND: Attention deficit disorder with or without hyperactivity (ADD) is present in 49% to 83% of patients with Tourette's syndrome (TS), and up to 50% of children with attention-deficit hyperactivity disorder (ADHD) have chronic tics or a family history of chronic tics. Two explanations have been offered for this association: (1) ADHD is part of the pleiotropic expression of the Gilles de la Tourette (Gts) gene(s), or (2) the presence of ADHD in TS is due to ascertainment bias. METHOD: To avoid ascertainment bias, we examined 338 first-degree relatives of 131 TS probands utilizing a structured questionnaire and the DSM-III criteria for ADD and DSM-III-R criteria for ADHD. All probands and many relatives were personally interviewed. RESULTS: Of the relatives with TS, 61% had ADD and 36% had ADHD. Of the relatives with chronic tics, 41% had ADD and 26% had ADHD. Log-linear analysis showed a major, significant association between tics and ADHD. CONCLUSION: These results indicate that ADHD is part of the pleiotropic expression of the Gts gene(s).

Attention Deficit Disorder with Hyperactivity↗
PubMed1991

The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders.

OBJECTIVE: --The A1 allele of the Taq I polymorphism of the dopamine D2 receptor (DRD2) gene has been earlier reported to occur in 69% of alcoholics, compared with 20% of controls. Other research has reported no significant difference in the prevalence of the A1 allele in alcoholics vs controls and no evidence that the DRD2 gene was linked to alcoholism. We hypothesized that these seemingly conflicting results might be because increases in the prevalence of the A1 allele may not be specific to alcoholism. Thus, we examined other disorders frequently associated with alcoholism or those believed to involve defects in dopaminergic neurotransmission. DESIGN: --Case comparison study. To minimize the effect of racial differences in gene frequencies, the study was restricted to non-Hispanic whites. SETTING: --Ambulatory and hospitalized patients. RESULTS: --Among all known controls (n = 314), 77 (24.5%) carried the A1 allele. Of the 69 controls known not to be alcoholics, 10 (14.5%) carried the A1 allele. The prevalence of the A1 allele was significantly increased in patients with Tourette's syndrome (44.9%, n = 147), attention deficit hyperactivity disorder (46.2%, n = 104), autism (54.5%, n = 33), alcoholism (42.3%, n = 104), and posttraumatic stress disorder (45.7%, n = 35). After correction for multiple comparisons (requiring P less than .0009 for significance), all remained significant except posttraumatic stress disorder. The prevalence of the A1 allele was not significantly increased in patients with depression, panic attacks, Parkinson's disease, or obesity. The prevalence of the A1 allele in drug addiction and schizophrenia was only significant when compared with that of controls who were not alcoholics, and no correction was made for multiple comparisons. CONCLUSION: --These results suggest the A1 allele of the DRD2 gene is associated with a number of behavior disorders in which it may act as a modifying gene rather than as the primary etiological agent.

Alcoholism↗
PubMed1991

Partial deletion of chromosome 6p: delineation of the syndrome.

Here we summarize the clinical findings of five new patients and nine patients reported in the literature with deletions of the short arm of chromosome 6. The del(6p) syndrome appears to include the following clinical findings: mental retardation, microcephaly, abnormal sutures, broad nasal bridge, various eye and ear abnormalities, a short neck with excess skin folds, and a normal birth weight and length.

Abnormalities, Multiple↗
PubMed1991

Clinical and genetic relationships between autism-pervasive developmental disorder and Tourette syndrome: a study of 19 cases.

Children with autism or pervasive developmental disorder (PDD) and Tourette syndrome (TS) share a number of symptoms. Forty-one cases have been reported in which PDD patients subsequently developed TS. We term this PDD----TS. We describe an additional 16 such patients plus 3 families where a close relative of a TS proband had autism. There was a high frequency of alcoholism, drug abuse, obsessive-compulsive, and other behavior disorders in the relatives of these patients. This frequency was virtually identical to that observed in relatives of individuals with TS only. We suggest there is an intimate genetic, neuropathologic relatedness between some cases of PDD and TS. Many observations have led us to suggest that the genetic defect in TS may be a mutation of tryptophan oxygenase and that TS is inherited as a semidominant semirecessive trait, i.e., homozygosity for a common gene which shows some expression in the heterozygous state. We propose that some types of PDD are inherited in the same fashion and by the same gene. This would explain the similarity of symptoms, frequent evolution of PDD into TS, the apparent recessive inheritance of PDD despite no increase in consanguinity, the high frequency of behavior problems in the relatives of PDD----TS patients and the serotonin abnormalities.

Adolescent↗
PubMed1991

Human tryptophan oxygenase localized to 4q31: possible implications for alcoholism and other behavioral disorders.

A human tryptophan oxygenase clone was isolated by screening a liver cDNA library with a rat tryptophan oxygenase cDNA clone. Analysis showed extensive homology between the rat and the human DNA and protein sequences. The combined use of cell hybrids and in situ hydridization indicated that human tryptophan oxygenase was localized to chromosome band 4q31. The tryptophan oxygenase gene may be important in some human behavior disorders, especially those associated with abnormalities of serotonin metabolism.

Alcoholism↗
PubMed1990

Blood serotonin and tryptophan in Tourette syndrome.

Blood serotonin and tryptophan levels were studied in 1,440 individuals. These included patients with Tourette syndrome (TS), attention deficit hyperactivity disorder (ADHA), or ADHD with a family history of TS (ADHD 2 degrees TS); relatives (parents, sibs) of these patients; other patients with TS-like disorders; and controls. There were significant decreases in the serotonin/platelet ratio (P = 0.0001) and in tryptophan (P less than 0.0001) in unmedicated patients with TS. Parents of TS patients showed a comparable, significant decrease in serotonin/platelet ratio (P less than 0.0001) and in tryptophan (P less than 0.0001), and there was no difference between parents with and without symptoms. This suggested that these were trait markers for the Gts gene and agrees with the proposal that TS patients are homozygous for Gts gene and that both parents are Gts gene carriers. Although there was no decrease in the serotonin/platelet ratio in ADHD patients, tryptophan levels were significantly decreased and there was a significant decrease in both the serotonin/platelet ratio and in tryptophan in the parents of patients with ADHD including those without a family history of TS. This is consistent with a close link between TS and ADHD. The basic defect may be a dysregulation of serotonin metabolism. The low blood serotonin and tryptophan levels in TS are consistent with the wide range of behavioral disorders seen in TS and suggest tryptophan oxygenase as a possible candidate gene.

Adult↗
PubMed1990

Prenatal determinations of paternity by molecular genetic "fingerprinting".

Clinical situations that require determining the paternity of a fetus are diagnostic dilemmas. Numerous technical problems have significantly hampered the ability to make accurate predictions on tissues obtained early in gestation. Applying the technique of molecular genetic "fingerprinting" in two gestations in which parentage was uncertain, we found that paternity can be established readily using DNA obtained from amniocytes or chorionic villi. The accuracy of this method exceeds that of conventional protein-based assays and is not decreased by variations in gene expression. Multiple analyses can be performed on restriction endonuclease digests of DNA present in very small amounts of cellular material normally obtained by routine prenatal diagnostic techniques. The simplicity, speed, reliability, and accuracy of molecular genetic analysis make it ideally suited to address questions of familial relationship in the prenatal period.

Adult↗
PubMed1990

An epidemiologic study of Tourette's syndrome in a single school district.

To evaluate the frequency of Gilles de la Tourette's syndrome (TS) in children, 3034 students in three schools in a single school district in greater Los Angeles were monitored frequently over a 2-year period by a school psychologist thoroughly familiar with the symptoms of the disorder. A portion of the cases were also evaluated in a TS clinic. A total of 14 males fulfilled the Tourette Syndrome Association research criteria for definite TS. When corrected for the number of students in special education classes in the monitored schools, the frequency of definite TS in males was 1 in 152. An additional 7 males who differed only in that they were not observed for a full year were termed definite TS less than 1 year. When the two groups were combined, the frequency of definite TS was 1 in 95 for males and 1 in 759 for females. These figures do not include an additional 10 males diagnosed as having definite transient tic disorder, 2 males diagnosed as having probable TS, and 10 males diagnosed as having possible TS. In addition to tics, most of these children had problems with attention span, obsessive compulsive behavior, and learning and/or conduct disorders. Seventy percent of the students with definite TS or definite TS less than 1 year were in special education classes. Twelve percent of the children in special education classes had definite TS or definite TS less than 1 year, and 28% were in one of the diagnostic categories of definite, probable, or possible. All of the 10 definite TS patients that were seen in the clinic had attention-deficit hyperactivity disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

A controlled family history study of Tourette's syndrome, I: Attention-deficit hyperactivity disorder and learning disorders.

Gilles de la Tourette's syndrome (TS) is a common, hereditary neuropsychiatric disorder. While its diagnostic feature is the presence of suppressible motor and vocal tics, a wide range of impulsive, compulsive, attentional, learning, mood, and anxiety disorders are also present in many patients. To determine if attentional and learning problems are part of the expression of the Gts gene (or genes), the authors analyzed family histories of 130 TS probands with 1851 relatives and 25 control probands with 541 relatives--a total of 2392 relatives. The frequency of attention-deficit hyperactivity disorder (ADHD) or learning disorders was significantly increased in the relatives of the TS probands. The data on first-degree relatives suggest that when the Gts gene is expressed in this form, in two thirds of the cases tics are also present and in one third they are not. These observations are consistent with the proposal that ADHD and learning disorders form an integral part of the expression of the Gts gene or genes.

Adolescent↗
PubMed1990

A controlled family history study of Tourette's syndrome, II: Alcoholism, drug abuse, and obesity.

The behaviors associated with Gilles de la Tourette's syndrome (TS), including impulsive, compulsive, attentional, learning, conduct, and mood disorders, have often been described as substrates for the development of alcoholism and/or drug abuse. As the authors' experience with TS pedigrees indicated that alcoholism and/or drug abuse were common in relatives of TS probands, they examined, by the family history technique, 1750 relatives over 14 years of age in 130 TS proband and 25 control families. Significant, life-disrupting problems with alcoholism and/or drug abuse were present in 14.5% of the relatives of TS probands compared with 4.4% of the control relatives (p less than .00001). Among parents of TS probands, the ratio of affected fathers to mothers was 2:1. Marked obesity (greater than 100 lb) was present in 10.8% of the mothers and 3.2% of all relatives of TS probands compared with 0.8% of all control relatives (p = .01). In parents of TS probands, the ratio of marked obesity in fathers to that in mothers was 1:4.5. When the categories of alcoholism and/or drug abuse and marked obesity were combined, 17.4% of all relatives of TS probands were affected compared with 4.6% of all control relatives (p less than .0001) and the ratio of fathers to mothers with these disorders was 1.1:1. Among all relatives of TS probands, 20.8% of those with tics and 17.4% of those without tics had problems with alcoholism and/or drug abuse or obesity or both. This finding suggests that when the Gts gene(s) is expressed in this form it is about equally likely to occur in persons with and persons without tics. The similarities between TS and early onset, male predominant, Type II alcoholism suggest that in some cases, alcoholism and/or drug abuse in males and severe obesity in females are related, genetically controlled, compulsive behaviors.

Adolescent↗
PubMed1990

A controlled family history study of Tourette's syndrome, III: Affective and other disorders.

In a family history study, the frequency of affective disorders was significantly higher for all relatives of Gilles de la Tourette's syndrome (TS) patients than for all relatives of controls. Among the relatives of TS patients, the presence of any behavior disorder was significantly more frequent for first-, second-, and third-degree relatives and total relatives. Among all relatives, 30.6% of the relatives of TS patients versus 6.1% of control relatives (p less than .0001) had some behavior disorder. Studies of first-degree relatives suggest that among those individuals expressing the Gts gene as some type of behavioral problem, about half have tics and half do not. These observations suggest that in addition to tics that Gts gene(s) can be expressed as a spectrum of behavioral disorders.

Age Factors↗
PubMed1989

Hypothesis: homozygosity in Tourette syndrome.

We review evidence suggesting that many individuals with Tourette syndrome (TS) may be homozygous for a "Tourette syndrome" gene. This is based on experience with pedigrees on 1,200 TS families, comparison of the occurrence of tics or associated behaviors such as obsessive-compulsive behavior, panic attacks, attention deficit hyperactivity disorder, and/or severe alcohol or drug abuse, on both the maternal and paternal side in 170 TS families compared to control families, biochemical studies of blood serotonin and tryptophan levels, and other evidence. These observations suggest the inheritance in TS may be best described as semi-dominant, semi-recessive. Some of the implications of this proposal are discussed.

Adult↗