Chromosomal translocation in a family with ocular anomalies: indications for karyotype analysis
- R V Jamieson1,
- L Gaunt2,
- D Donnai2,
- G C M Black2,
- B Kerr3,
- O Stecko3,
- G C M Black4
- 1Academic Unit of Medical Genetics and Regional Genetic Service, St Mary’s Hospital, Manchester, M13 0JH, UK, and Department of Clinical Genetics, and Sydney University Department of Paediatric and Child Health, The Children’s Hospital at Westmead, Sydney, NSW, 2145, Australia
- 2Academic Unit of Medical Genetics and Regional Genetic Service, St Mary’s Hospital, Manchester, M13 0JH, UK
- 3Royal Manchester Children’s Hospital, Manchester, UK
- 4Academic Unit of Ophthalmology, Manchester Royal Eye Hospital, Manchester, M13 9WH, UK
- Correspondence to: R V Jamieson; robynj{at}chw.edu.au
- Accepted 4 September 2002
Hereditary isolated congenital malformations such as congenital cataracts or anterior segment anomalies are usually considered to be the result of a single gene mutation. The identification of associated abnormalities—dysmorphic features, a malformation in another organ system, or mental handicap, help to identify those who carry more severe genetic defects such as chromosome rearrangements. We describe a family where two otherwise healthy men, a father and son, had juvenile cataracts. They both had offspring with more severe ocular anomalies including anterior segment dysgenesis, as well as mental retardation and dysmorphic features. Recent karyotype analysis revealed a balanced translocation in both father and son and a derived unbalanced translocation in their more severely affected children. Analysis of the translocation breakpoints led to the identification of a new human disease gene, MAF, in lens and anterior segment development.1 Critically, for the family, the finding of the translocation provides an explanation for the severe ocular and other anomalies in the individuals with the unbalanced derivative karyotype. In addition, it allows the option of prenatal diagnosis for future offspring for individuals carrying the balanced translocation.
Family report
A man with juvenile onset cataracts, and a family history of this, sought genetic advice with his partner. This man (II.3, Fig 1) was the father of three children with ocular anomalies and developmental delay. He had juvenile onset, progressive cataracts which were removed at the age of 24 years. The cataracts were described as widespread dot opacities, with anterior and posterior sutural densities. General and other ocular examination was normal.
Pedigree …
