Turner syndrome is a human genetic disorder involving females who lack all or part of one X chromosome. The principle features are short stature, infertility, and anatomic abnormalities that include webbed neck, congenital heart disease, and renal and skeletal malformations. Selected neurocognitive deficits, including impaired visual-spatial abilities, are also characteristic of Turner syndrome, but global developmental delay is uncommon. As a relatively common genetic disorder with well-defined manifestations, Turner syndrome presents the opportunity to investigate genetic factors that influence female physical and cognitive development There is potentially informative genetic and phenotypic variation among Turner syndrome subjects with partial X deletions (partial monosomy X). Careful clinical and molecular characterization of these unusual subjects who represent """"""""experiments of nature"""""""" could link individual Turner syndrome phenotypic features to specific X chromosome regions. Similar studies are in progress for Down syndrome and other chromosome disorders. Turner syndrome is an excellent model for such phenotype mapping studies because of its prevalence, the well-characterized phenotype, and the wealth of molecular resources available for the X chromosome. The disorder is also a model for studying genetic aspects of cognition because of the selective nature of neurocognitive deficits and the relative sparing of verbal abilities. This study will examine approximately 80 partial monosomy X subjects. Each subject will have a thorough clinical evaluation and extensive neurocognitive testing to determine the presence or absence of specific Turner syndrome phenotypic features. Cell lines will be established and used for molecular studies to precisely define the subjects' X deletions. The goal of this study is to define critical regions of the X chromosome for neurocognitive deficits and physical features associated with Turner syndrome. Phenotype mapping of X deletions will be helpful for genetic counseling and for predicting which girls with Turner syndrome are at high risk for learning difficulties; these children and their parents might benefit from extra social, psychological, and educational support. The collection of cell lines will also provide a valuable resource for future studies aimed at identifying specific Turner syndrome genes. Characterization of these genes would provide insight into the pathophysiology of Turner syndrome as well as processes of normal physical and cognitive development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS035554-03S2
Application #
6070018
Study Section
Human Development and Aging Subcommittee 3 (HUD)
Program Officer
Nichols, Paul L
Project Start
1997-03-01
Project End
2002-02-28
Budget Start
1999-03-01
Budget End
2000-02-29
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
Gordon, Derek; Zinn, Andrew R (2009) Computing power of quantitative trait locus association mapping for haploid loci. BMC Bioinformatics 10:261
Zinn, Andrew R; Kushner, Harvey; Ross, Judith L (2008) EFHC2 SNP rs7055196 is not associated with fear recognition in 45,X Turner syndrome. Am J Med Genet B Neuropsychiatr Genet 147B:507-9
Simon, T J; Takarae, Y; DeBoer, T et al. (2008) Overlapping numerical cognition impairments in children with chromosome 22q11.2 deletion or Turner syndromes. Neuropsychologia 46:82-94
Campos-Barros, Angel; Benito-Sanz, Sara; Ross, Judith L et al. (2007) Compound heterozygosity of SHOX-encompassing and downstream PAR1 deletions results in Langer mesomelic dysplasia (LMD). Am J Med Genet A 143A:933-8
Bondy, Carolyn A; Matura, Lea Ann; Wooten, Nicole et al. (2007) The physical phenotype of girls and women with Turner syndrome is not X-imprinted. Hum Genet 121:469-74
Russell, Heather F; Wallis, Deeann; Mazzocco, Michele M M et al. (2006) Increased prevalence of ADHD in Turner syndrome with no evidence of imprinting effects. J Pediatr Psychol 31:945-55
Van, Phillip L; Bakalov, Vladimir K; Zinn, Andrew R et al. (2006) Maternal X chromosome, visceral adiposity, and lipid profile. JAMA 295:1373-4
Zinn, Andrew R; Ramos, Purita; Ross, Judith L (2006) A second recombination hotspot associated with SHOX deletions. Am J Hum Genet 78:523-5
Ross, Judith L; Kowal, Karen; Quigley, Charmian A et al. (2005) The phenotype of short stature homeobox gene (SHOX) deficiency in childhood: contrasting children with Leri-Weill dyschondrosteosis and Turner syndrome. J Pediatr 147:499-507
Boycott, Kym M; Parslow, Malcolm I; Ross, Judith L et al. (2003) A familial contiguous gene deletion syndrome at Xp22.3 characterized by severe learning disabilities and ADHD. Am J Med Genet A 122A:139-47

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