title: Screening of PAX6 gene in Italian congenital aniridia patients revealed four novel mutations.
abstract: To uncover underlying mutations in a cohort of Italian patients with aniridia, a rare congenital panocular condition with an incidence ranging from 1:64,000 to 1:100,000. The disease may be found isolated or in association with other syndromes characterized by partial or complete absence of the iris and iris hypoplasia.
  
  
  
  We analyzed the PAX6 gene in 11 patients with aniridia fulfilling the following inclusion criteria: partial or complete absence of the iris and age < 18 years at the time of diagnosis. DNA sequence analysis was integrated with Multiple Ligation Probe Assay (MLPA) analysis.
  
  
  
  We identified seven PAX6 mutations, including four novel ones. The majority of mutations lie in the DNA-binding domain and all produce a truncated protein. All tested patients did not have WT1 gene deletions thus excluding the WAGR syndrome. We present the clinical findings in the four cases harboring novel mutations. We were unable to identify mutations in four cases with complete aniridia thus indicating that other gene/s could be involved in the disease.
  
  
  
  It is important to establish the molecular diagnosis early to avoid repeated and long-term screening for Wilms tumor. Our work further emphasizes that a wide range of ocular phenotypes are associated with loss of function PAX6 mutations. In addition to the possibility of stochastic variations, other genetic variations could play a role as modifier genes, thus giving rise to the observed different ocular phenotypes.
authors: a Department of Laboratory Medicine , Medical Genetics, Niguarda Ca' Granda Hospital , Milan , Italy.
authors: Paola
authors: P
authors: Primignani
authors: b Pediatric Ophthalmology, Niguarda Ca' Granda Hospital , Milan , Italy.
authors: Davide
authors: D
authors: Allegrini
authors: a Department of Laboratory Medicine , Medical Genetics, Niguarda Ca' Granda Hospital , Milan , Italy.
authors: Emanuela
authors: E
authors: Manfredini
authors: c Department of Laboratory Medicine , Pathology and Cytogenetics, Niguarda Ca' Granda Hospital , Milan , Italy.
authors: Lorenza
authors: L
authors: Romitti
authors: a Department of Laboratory Medicine , Medical Genetics, Niguarda Ca' Granda Hospital , Milan , Italy.
authors: Lucia
authors: L
authors: Mauri
authors: a Department of Laboratory Medicine , Medical Genetics, Niguarda Ca' Granda Hospital , Milan , Italy.
authors: Maria Cristina
authors: MC
authors: Patrosso
authors: a Department of Laboratory Medicine , Medical Genetics, Niguarda Ca' Granda Hospital , Milan , Italy.
authors: Emanuela
authors: E
authors: Veniani
authors: d Institute of Genetics, Azienda Ospedaliero-Universitaria Udine , Udine , Italy.
authors: Alessandra
authors: A
authors: Franzoni
authors: b Pediatric Ophthalmology, Niguarda Ca' Granda Hospital , Milan , Italy.
authors: Alessandra
authors: A
authors: Del Longo
authors: a Department of Laboratory Medicine , Medical Genetics, Niguarda Ca' Granda Hospital , Milan , Italy.
authors: Giovanni Pietro
authors: GP
authors: Gesu
authors: b Pediatric Ophthalmology, Niguarda Ca' Granda Hospital , Milan , Italy.
authors: Elena
authors: E
authors: Piozzi
authors: d Institute of Genetics, Azienda Ospedaliero-Universitaria Udine , Udine , Italy.
authors: Giuseppe
authors: G
authors: Damante
authors: a Department of Laboratory Medicine , Medical Genetics, Niguarda Ca' Granda Hospital , Milan , Italy.
authors: Silvana
authors: S
authors: Penco
mesh_terms: D015783:Aniridia / Q000175:diagnosis / Q000235:genetics*; D002386:Cataract / Q000175:diagnosis; D002648:Child; D002675:Child, Preschool; D005260:Female; D005901:Glaucoma / Q000175:diagnosis; D006801:Humans; D007223:Infant; D007558:Italy; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D009759:Nystagmus, Pathologic / Q000175:diagnosis; D000071841:PAX6 Transcription Factor / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human
keywords: Aniridia; PAX gene; medical genetics