Mutation in the CSB gene in a patient with Cerebro-Oculo-Facio-Skeletal syndrome

Abstract

Cerebro-Oculo-Facio-Skeletal (COFS) syndrome is an autosomal recessive multiple malformation syndrome with congenital microcephaly, microphthalmia and cataracts, characteristic facial features, camptodactyly and rocker-bottom feet. Survival is usually less than 5 years. Cockayne syndrome is an autosomal recessive condition with dwarfism, precocious senile appearance, eye abnormalities and mental retardation. Features are usually not apparent until 2-4 years of age. Two complementation groups have been identified (CS-A and CS-B) and both genes have been characterized. There is an early onset form of Cockayne syndrome (EOCS) and it has been suggested that EOCS and COFS may be the same condition. Recently a mutation in the CSB gene has been reported in two related patients with the COFS phenotype.We describe a patient with congenital microcephaly, microphthalmia, prominent nose, micrognathia, large ears, small mouth with upper lip overlapping lower lip, joint contractures, rockerbottom feet, congenital cataracts, and profound growth and developmental retardation. At age 2 years 10 months she developed seizures, proteinuria, and acute renal failure and died. The family history is notable for a female sibling with identical clinical features who died at age 3 of nephrotic syndrome. There is no reported consanguinity. DNA sequence analysis of the CSB gene in fibroblasts from this patient revealed a homozygous 177 bp deletion in exon 10.This is a different mutation than that previously reported in COFS syndrome and provides further evidence that COFS syndrome is caused by mutations in the CSB gene. Patients identified with the COFS phenotype should have UV sensitivity studies and analysis of the CSB gene; identification of a mutation would provide a method for prenatal diagnosis in subsequent pregnancies and for carrier testing.