A family pedigree reveals first- and second-generation female relatives with premature menopause and male relatives with a progressive neurodegenerative disorder starting by their sixth decade. There are more males than females exhibiting mental retardation from childhood by the fourth generation. Genetic analysis of affected persons reveals CGG repeat expansions in a gene encoding for a protein that binds mRNA transcripts in neurons and shuttles them to the synapses. An abnormality involving which of the following organs is most likely to be present in affected males?
This family has fragile X syndrome. Anticipation occurred, with premutations of limited triple repeat expansions present in the first two generations, whereas later generations had full mutations with larger CGG expansions. The FMR1 gene encodes for familial mental retardation protein (FMRP) expressed most abundantly in brain and testis, accounting for macro-orchidism in the latter. Absence of this protein in brain leads to increased mRNA translation that affects synaptic junctions and their function. The FMRP protein is widely expressed in other tissues such as those listed, but their function is not as markedly affected as brain and testis.
Adrenal
Pancreas
Pituitary
Testis
Genetics