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P#21
: Comings, D.E., Muhleman, D., Dietz, G.W., & Donlon, T. (1991). Human tryptophan oxygenase localized to 4q31: Possible implications for human behavioral disorders
ABSTRACT: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. Genomics, 9, 301-308.
Back to The Paper's Index PageP#23
: Comings, D.E., & Comings, B.G. (1993). Sexual abuse or Tourette syndrome?
ABSTRACT:In addition to motor and vocal tics, Tourette syndrome (TS) can be associated with a wide range of behavioral problems including attention deficit hyperactivity disorder, obsessive-compulsive behaviors, learning disabilities, conduct disorder, and inappropriate sexual behaviors. The latter, which occur in a minority of patients, can include coprolalia, copropraxia, coprographia, exhibitionism, compulsive masturbation, touching themselves or others in the crotch or breast, and sexually self-abusive behaviors. Children who display these behaviors are often assumed to have been sexually abused. When teachers, social service agencies, or other professionals are not familiar with TS, injustice to families can occur. Professionals should be aware that TS can be an alternative to sexual abuse as an explanation of such behaviors.Social Work, 38, 347-350.
Back to The Paper's Index PageP#24
: Comings, D.E., & Comings, B.G. (1993). SIDS and Tourette syndrome: Is there an etiologic relationship?
ABSTRACT:SIDS has been repeatedly linked to the presence of prolonged sleep apnea and defective arousal mechanisms. Multiple cases of SIDS may occur in some families, and siblings of SIDS infants are at a 3 to 10 times greater risk of SIDS than the general population. This suggests genetic factors can play a role. Sleep laboratory studies of adults with Tourette syndrome (TS) show that 23% have sleep apnea and 29% have abnormal arousals. Disorders of arousal such as enuresis, sleep walking, sleep talking and night terrors are common in children with TS. We report seven TS families in which one or more close relatives died of SIDS, or had apparent life-threatening episode (ALTE) and required apnea monitoring. Serotonin is the major neurotransmitter involved in sleep regulation and abnormalities of serotonin have been implicated in both SIDS and TS. These and other observations suggest that the Tourette syndrome gene (Gts) may be the genetic factor contributing to an increased risk of SIDS. J.Dev.Physical Disabil., 5, 265-279.
Back to The Paper's Index PageP#25
: Knell, E., & Comings, D.E. (1993). Tourette syndrome and attention deficit hyperactivity disorder: Evidence for a genetic relationship
ABSTRACT: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). J.Clin.Psychiat., 54, 331-337.
Back to The Paper's Index PageP#27
: Comings, D.E., Flanagan, S.D., Dietz, G., Muhleman, D., Knell, E., & Gysin, R. (1993). The dopamine D2 receptor (DRD2) as a major gene in obesity and height
ABSTRACT: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). Biochem.Med.Metabolic Biol., 50, 176-185.
Back to The Paper's Index PageP#30
: Comings, D.E. (1994). Genetic factors in substance abuse based on studies of Tourette syndrome and ADHD probands and relatives. I. Drug abuse.
ABSTRACT:There have been relatively few studies of genetic factors in drug abuse. Childhood Attention Deficit Hyperactivity Disorder (ADHD) has been implicated as a risk factor, and pedigree studies of Tourette Syndrome (TS), a hereditary impulse disorder closely related to ADHD, show an increased prevalence of substance abuse in relatives. These observations suggest the genes for TS and ADHD may play an important role in the development of drug abuse. To examine this hypothesis 217 TS probands and 328 of their relatives, 58 ADHD probands and 35 of their relatives, and 50 controls were prospectively studied using a structured questionnaire based on the Diagnostic Interview Schedule. All subjects were Caucasians 16 to 49 years of age. The responses concerning the use of 8 different drugs and 8 different symptoms of drug abuse were compared. The results showed a highly significant increase in positive responses with increased loading for the TS and ADHD genes for 6 of the 8 drugs and all of the drug abuse symptoms. The percentage of positive responses in TS probands was markedly influenced by the presence of comorbid ADHD, as well as discipline, obsessive-compulsive, or alcohol problems. These results suggest that the genes responsible for TS and ADHD play an important role in drug abuse/dependence. The dopamine D2 receptor gene (DRD2) appears to be one of these genes since variants at this locus are significantly increased in frequency in TS, ADHD, conduct disorder and drug abuse. Drug and Alcohol Dependence, 35, 1-16.
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