Fragile X mental retardation gene (Fmr1) knock-out (KO) mice display core deficits of FXS, including abnormally increased sound-evoked responses, and show a delayed development of parvalbumin (PV) cells.
Overall results enable us to conclude that the developmental delay is the cumulative result of a methylated FMR1 full mutation on the active X-chromosome and the inactivation of the other homologue carrying the de novo 439 kb deletion.
The mechanism of pathogenesis contributing significantly to our patient's clinical findings may relate to interaction between TOP3B and fragile X mental retardation protein (FMRP), an mRNA-binding protein that regulates translation and is altered in fragile X syndrome, a condition involving developmental delay, learning disability, and autism.
Missense mutations in the FMR1 gene might account for a considerable proportion of cases in male patients with FXS-related symptoms, such as those linked to mental retardation and developmental delay.
In addition, we find that there is a 9‑fold greater likelihood of detecting clinically significant chromosomal aberrations than of detecting a full Fragile X mental retardation 1 (FMR1) gene CGG repeat expansion in cases referred on the basis of DD.
A literature review revealed rare cases with similar deletions that included IDS and FMR1 in females with developmental delay, variable features of Hunter syndrome, and skewed X-inactivation of the normal X chromosome.
These findings greatly expand the catalog of known FMR1 sequence variants and suggest that FMR1 sequence variants may represent an important cause of developmental delay.