A Turner syndrome neurocognitive phenotype maps to Xp22.3
Andrew R Zinn1, David Roeltgen, Gerry Stefanatos
1Eugene McDermott Center for Human Growth and Development and Department of Internal Medicine, The University of Texas Southwestern Medical School, Dallas TX, USA. andrew.zinn@utsouthwestern.edu
Behavioral and Brain Functions : BBF
|May 23, 2007
Summary
Turner syndrome (TS) neurocognitive deficits are linked to Xp22.3 gene deletions. This study confirms haploinsufficiency in this region causes visual-spatial impairments in women with TS.
Area of Science:
- Genetics
- Neuroscience
- Human Biology
Background:
- Turner syndrome (TS) is characterized by a neurocognitive phenotype, including impaired visual-spatial abilities.
- Previous research suggested haploinsufficiency of genes on distal Xp causes this phenotype.
- This study aimed to validate these findings in a larger cohort of adult women with partial Xp or Xq deletions.
Purpose of the Study:
- To confirm that deletions in distal Xp are sufficient to cause the neurocognitive phenotype observed in Turner syndrome.
- To identify the specific genetic region responsible for the nonverbal deficits in TS.
- To investigate the relationship between genetic deletions and other TS features like ovarian function and stature.
Main Methods:
- Recruitment of 47 adult women with partial Xp or Xq deletions from North American clinics.
- Comprehensive phenotype assessment including stature, ovarian function, and detailed neurocognitive testing using the Turner Syndrome Cognitive Summary (TSCS) score.
- Advanced genetic analyses including karyotyping, X inactivation studies, FISH, microsatellite genotyping, and array CGH.
Main Results:
- Statistical evidence indicates that deletion of the Xp22.3 region is sufficient to cause the TS neurocognitive phenotype (measured by TSCS score).
- The TSCS score was not associated with ovarian failure, short stature, X inactivation pattern, or subject's age.
- This critical region encompasses 31 annotated genes.
Conclusions:
- Detailed mapping implicates haploinsufficiency of one or more genes within the 8.3 Mb Xp22.3 region as the cause of the TS neurocognitive phenotype.
- Genes STS and NLGN4X, located proximal to PAR1 within this critical region, are strong candidates for causing these neurocognitive deficits.
- Haploinsufficiency of the SHOX gene in PAR1 is unlikely to be responsible for the TS neurocognitive phenotype.
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