BACKGROUND: The authors recently identified three large genetically unrelated families with an identical 17 base pair duplication mutation in exon 4 of the PITX3 gene. Here, they report the detailed clinical phenotype. METHODS: Affected and unaffected individuals in the three families with autosomal dominant posterior polar cataract underwent full clinical examination and donated blood samples for DNA extraction and molecular genetic studies. RESULTS: In all three families, an identical 17 base pair duplication mutation in PITX3 was identified which co-segregated with disease status in the family. All affected individuals had bilateral progressive posterior polar cataracts. In one family, posterior polar cataract was the only clinical abnormality but in the other two families, one of 10 affected individuals and four of 11 affected individuals also had anterior segment mesenchymal dysgenesis (ASMD). CONCLUSION: Mutations in the PITX3 gene in humans result in posterior polar cataract and variable ASMD. The gene encodes a transcription factor which has a key role in lens and anterior segment development. The mechanism by which the mutant protein gives rise to such a regional pattern of lens opacity remains to be elucidated.
BACKGROUND: The authors recently identified three large genetically unrelated families with an identical 17 base pair duplication mutation in exon 4 of the PITX3 gene. Here, they report the detailed clinical phenotype. METHODS: Affected and unaffected individuals in the three families with autosomal dominant posterior polar cataract underwent full clinical examination and donated blood samples for DNA extraction and molecular genetic studies. RESULTS: In all three families, an identical 17 base pair duplication mutation in PITX3 was identified which co-segregated with disease status in the family. All affected individuals had bilateral progressive posterior polar cataracts. In one family, posterior polar cataract was the only clinical abnormality but in the other two families, one of 10 affected individuals and four of 11 affected individuals also had anterior segment mesenchymal dysgenesis (ASMD). CONCLUSION: Mutations in the PITX3 gene in humans result in posterior polar cataract and variable ASMD. The gene encodes a transcription factor which has a key role in lens and anterior segment development. The mechanism by which the mutant protein gives rise to such a regional pattern of lens opacity remains to be elucidated.
Authors: V Berry; P Francis; M A Reddy; D Collyer; E Vithana; I MacKay; G Dawson; A H Carey; A Moore; S S Bhattacharya; R A Quinlan Journal: Am J Hum Genet Date: 2001-09-27 Impact factor: 11.025
Authors: R S Smith; A Zabaleta; T Kume; O V Savinova; S H Kidson; J E Martin; D Y Nishimura; W L Alward; B L Hogan; S W John Journal: Hum Mol Genet Date: 2000-04-12 Impact factor: 6.150
Authors: Robyn V Jamieson; Rahat Perveen; Bronwyn Kerr; Martin Carette; Jill Yardley; Elise Heon; M Gabriela Wirth; Veronica van Heyningen; Di Donnai; Francis Munier; Graeme C M Black Journal: Hum Mol Genet Date: 2002-01-01 Impact factor: 6.150
Authors: Hannah Verdin; Elena A Sorokina; Françoise Meire; Ingele Casteels; Thomy de Ravel; Elena V Semina; Elfride De Baere Journal: Orphanet J Rare Dis Date: 2014-02-20 Impact factor: 4.123