Genotype differences in cognitive functioning in Noonan syndrome
Autor: | Elizabeth I. Pierpont, Erica Tworog-Dube, Mark S. Seidenberg, Mary Ella M Pierpont, Nancy J. Mendelsohn, Amy E. Roberts |
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Rok vydání: | 2009 |
Předmět: |
Male
Proto-Oncogene Proteins B-raf Adolescent Genotype Developmental Disabilities DNA Mutational Analysis Protein Tyrosine Phosphatase Non-Receptor Type 11 Neuropsychological Tests Article Developmental psychology Cohort Studies Behavioral Neuroscience Borderline intellectual functioning Genetics medicine Humans Genetic Predisposition to Disease Genetic Testing Cognitive skill Child Hearing Loss Genetic testing medicine.diagnostic_test Noonan Syndrome Genetic disorder Cognition medicine.disease Motor Skills Disorders PTPN11 Neurology Child Preschool Mutation Educational Status Noonan syndrome Female Cognition Disorders SOS1 Protein Psychology Clinical psychology |
Zdroj: | Genes, Brain and Behavior. 8:275-282 |
ISSN: | 1601-183X 1601-1848 |
Popis: | Noonan syndrome (NS) is an autosomal dominant genetic disorder associated with highly variable features, including heart disease, short stature, minor facial anomalies and learning disabilities. Recent gene discoveries have laid the groundwork for exploring whether variability in the NS phenotype is related to differences at the genetic level. Here we examine the influence of both genotype and non-genotypic factors on cognitive functioning. Data are presented from 65 individuals with Noonan syndrome (ages 4 to 18) who were evaluated using standardized measures of intellectual functioning. The cohort included 33 individuals with PTPN11 mutations, 6 individuals with SOS1 mutations, 1 individual with a BRAF mutation, and 25 participants with negative, incomplete or no genetic testing. Results indicate that genotype differences may account for some of the variation in cognitive ability in NS. Whereas cognitive impairments were common among individuals with PTPN11 mutations and those with unknown mutations, all of the individuals with SOS1 mutations exhibited verbal and nonverbal cognitive skills in the average range or higher. Participants with N308D and N308S mutations in PTPN11 also demonstrated no (or mild) cognitive delays. Additional influences such as hearing loss, motor dexterity and parental education levels accounted for significant variability in cognitive outcomes. Severity of cardiac disease was not related to cognitive functioning. Our results suggest that some NS-causing mutations have a more marked impact on cognitive skills than others. |
Databáze: | OpenAIRE |
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