Disease relevance of Frasier Syndrome

• KTS (lysine-threonine-serine) splice site mutations in WT1 intron 9 have been described in patients with Frasier syndrome, another rare syndrome defined by focal and segmental glomerulosclerosis (FSGS), XY pseudohermaphroditism, and frequent occurrence of gonadoblastoma [1].
• Denys-Drash syndrome (DDS) and Frasier syndrome (FS) are two related conditions caused by mutations of the Wilms tumor gene, WT1 [2].
• WT1 gene mutation responsible for male sex reversal and renal failure: the Frasier syndrome [3].
• Denys-Drash syndrome (DDS) and Frasier syndrome (FS) are rare diseases caused by the mutations of Wilms tumor gene, WT1 [4].

High impact information on Frasier Syndrome

• Donor splice-site mutations in WT1 are responsible for Frasier syndrome [5].
• Mutations within the +/-KTS splice junction lead to severe urogenital developmental abnormalities such as Frasier syndrome, indicating that the isoform ratio is critical for wild-type function [6].
• Exon 9 mutations in the WT1 gene, without influencing KTS splice isoforms, are also responsible for Frasier syndrome [7].
• Molecular analysis of the sex-determining region from the Y chromosome in two patients with Frasier syndrome [8].

Chemical compound and disease context of Frasier Syndrome

• We report a case where genetic analysis showed a WT1 mutation typically associated with Frasier syndrome: a 1228 + 5 guanine to adenine substitution at the 3' alternative splice donor site in intron 9 [9].

Gene context of Frasier Syndrome

• This observation is consistent with differential roles for the -KTS and +KTS variants of WT1 which have been postulated on the basis of human disorders such as the Frasier syndrome [10].

References