Frasier syndrome
Overview
Frasier syndrome: A rare syndrome involving kidney disease and male pseudohermaphrodism (genetic male with some female sex organs). Kidney failure can occur as early as adolescence
Symptoms
Female genitalia Kidney disease Excess protein in the urine Streak gonads
Treatment
Fragile X syndrome is an X-linked condition that doesn't follow a simple X-linked inheritance pattern. The normal sequence of the FMR1 gene was identified at Xq27.3 in 1991. The unique mutation that results in fragile X syndrome consists of an expanding region of a specific triplet of nitrogenous bases: cytosine, guanine, guanine (CGG) within the gene's deoxyribonucleic acid (DNA) sequence. Normally, FMR1 contains 6 to 50 sequential copies of the CGG triplet. When the number of CGG triplets expands to the range of 50 to 200 repeats, the region of DNA becomes unstable and is referred to as a premutation. A full mutation consists of over 200 CGG triplet repeats. The full mutation typically causes abnormal methylation (methyl groups attach to components of the gene) of FMR1. Methylation inhibits gene transcription and thus protein production. The reduced or absent protein product (FNIRP) is responsible for the clinical features of fragile X syndrome. Approximately 15% to 20% of males with a full mutation don't have fragile X. This may be explained by either the ability of unmethylated portions (of their mutated FMR1) to be transcribed for eventual protein production, or that these males are mosaic for the FMR1 premutation. In asymptomatic mosaic males it's believed that the cells with a premutation can produce enough protein to compensate for the cells that contain a full mutation and consequently produce no protein. Approximately 50% of females who inherit a full mutation from their mother have clinical features of fragile X syndrome. This is primarily due to the normal process of random X inactivation. At the time of meiosis, both X chromosomes must be activated. However, shortly after the zygote stage, an X chromosome is inactivated in every cell. Clinically measurable effects of the full FMR1 mutation will be more likely in relevant tissues or organs that have a disproportionate number of cells in which the normal X chromosome has been inactivated.