Microdeletions Including FMR1 in Three Female Patients with Intellectual Disability - Further Delineation of the Phenotype and Expression Studies
Autor: | Cornelia Kraus, N. Katzorke, Trine Prescott, S. Blichfeldt, J. Rehnitz, Eva Wohlleber, Hartmut Engels, Peter H. Vogt, Felix F. Brockschmidt, Stefanie Heilmann, Heiko Reutter, O.K. Rødningen, Per Hoffmann, Jennifer A. Lee, Zeynep Tümer, Kirstine Ravn, Martina Kreiß-Nachtsheim, Alexander M. Zink |
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Rok vydání: | 2014 |
Předmět: |
congenital
hereditary and neonatal diseases and abnormalities business.industry Point mutation Macrocephaly medicine.disease Bioinformatics FMR1 nervous system diseases Fragile X syndrome Medizinische Fakultät Speech delay Intellectual disability Genetics medicine Autism Original Article ddc:610 medicine.symptom Trinucleotide repeat expansion business Genetics (clinical) |
Zdroj: | Molecular Syndromology. 5:65-75 |
ISSN: | 1661-8777 1661-8769 |
Popis: | Fragile X syndrome (FXS) is one of the most common causes of intellectual disability/developmental delay (ID/DD), especially in males. It is caused most often by CGG trinucleotide repeat expansions, and less frequently by point mutations and partial or full deletions of the FMR1 gene. The wide clinical spectrum of affected females partly depends on their X-inactivation status. Only few female ID/DD patients with microdeletions including FMR1 have been reported. We describe 3 female patients with 3.5-, 4.2- and 9.2-Mb de novo microdeletions in Xq27.3-q28 containing FMR1. X-inactivation was random in all patients, yet they presented with ID/DD as well as speech delay, macrocephaly and other features attributable to FXS. No signs of autism were present. Here, we further delineate the clinical spectrum of female patients with microdeletions. FMR1 expression studies gave no evidence for an absolute threshold below which signs of FXS present. Since FMR1 expression is known to be highly variable between unrelated females, and since FMR1 mRNA levels have been suggested to be more similar among family members, we further explored the possibility of an intrafamilial effect. Interestingly, FMR1 mRNA levels in all 3 patients were significantly lower than in their respective mothers, which was shown to be specific for patients with microdeletions containing FMR1. |
Databáze: | OpenAIRE |
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