FMR1 Gene Expansion, Large Deletion of Xp, and Skewed X-Inactivation in a Girl With Mental Retardation and Autism
2010
Abstract
A genetic background of the disease in a female patient with mental retardation and autism is described. Full FMR1 mutation (expansion of CGG repeat in the 5’ untranslated region of the FMR1 gene, Xq27.3) was identified on one X chromosome and a large de novo deletion (17.4Mb, 90 genes) in Xp22 was found on the other X chromosome.
Manifestation of the disease was in accordance with the finding that both alleles of the FMR1 gene were almost completely methylated and therefore non-functional. The large deletion was the most probable cause of the X-inactivation skewing, thus explaining the methylation of not only the expanded (maternal) but also the normal (paternal) FMR1 alleles.