The goal of this application is to initiate genetic studies of a cohort of well characterized autistic patients already enrolled in a program project, titled """"""""Orbitofrontal-limbic dysfunction in autism"""""""". Autism is a neurodevelopmental disorder with considerable heterogeneity among affected children. This heterogeneity is due, to a large extent, to many known and unknown genetic factors. Therefore the neurobehavioral development and dysfunction in autism must be understood within a genetic context. Consequently this application will focus on recalling autistic patients and their families so a thorough medical genetics evaluation can be performed. Medical histories and physical examinations will enable the diagnosis of known and novel genetic syndromes. Specifically the frequency of macrocephaly, a physical finding associated with autism, will be assessed and correlated with cognitive functioning and genetic testing. Routine genetic studies will be performed, including G-banded karyotypes at the 550-600 band resolution, fragile X syndrome molecular testing, and plasma amino and urine organic acid analyses. Array Comparative Genomic Hybridization (CGH) will be performed on all mentally retarded and/or dysmorphic patients to screen for subtle, unrecognized genomic deletions or duplications. Metabolic studies will include the novel assessment of creatine metabolism. To further genetic studies, lymphoblastoid cell lines from patients and DNA from patients and parents will be banked. Patient DNA will be used to screen for novel mutations in the tuberous sclerosis complex genes TSC1 and TSC2. The specific role of these genes in autism is still unclear. Results from these studies will further delineate autistic phenotypes, allow the correlation of specific genetic lesions with data from other aspects of the program project, and provide a foundation for larger genetic studies of autism.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
1R03HD047659-01A1
Application #
6926309
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Kau, Alice S
Project Start
2005-04-15
Project End
2007-03-31
Budget Start
2005-04-15
Budget End
2006-03-31
Support Year
1
Fiscal Year
2005
Total Cost
$74,354
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Pediatrics
Type
Schools of Medicine
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225