The genetic architecture of aniridia and Gillespie syndrome

AbstractAbsence of part or all of the iris, aniridia, is a feature of several genetically distinct conditions. This review focuses on iris development and then the clinical features and molecular genetics of these iris malformations. Classical aniridia, a panocular eye malformation including foveal hypoplasia, is the archetypal phenotype associated with heterozygousPAX6 loss-of-function mutations. Since this was identified in 1991, many genetic mechanisms ofPAX6 inactivation have been elucidated, the commonest alleles being intragenic mutations causing premature stop codons, followed by those causing C-terminal extensions. Rarely, aniridia cases are  associated withFOXC1, PITX2 and/or their regulatory regions. Aniridia can also occur as a component of many severe global eye malformations.  Gillespie syndrome—a triad of partial aniridia, non-progressive cerebellar ataxia and intellectual disability—is phenotypically and genotypically distinct from classical aniridia. The causative gene has recently been identified asITPR1. The same characteristic Gillespie syndrome-like iris, with aplasia of the pupillary sphincter and a scalloped margin, is seen inACTA2-related multisystemic smooth muscle dysfunction syndrome. WAGR syndrome (Wilms tumour, aniridia, genitourinary anomalies and mental retardation/intellectual disability), is caused by contiguous deletion ofPAX6 andWT1 on chromosome 11p. Deletions encompassingBDNF have been causally implicated in the obesity and intellect...
Source: Human Genetics - Category: Genetics & Stem Cells Source Type: research