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Germline and somatic mosaicism in achondroplasia
  1. *Cellular Genetics Group, Oxford University, Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK
  2. †Department of Clinical Genetics, The New Children's Hospital, Sydney, NSW 2124, Australia
  1. Dr Henderson,shenderson{at}

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Editor—We describe a sib recurrence in achondroplasia with parents of normal stature. Both affected offspring carry the same causal mutation (G1138C) in the fibroblast growth factor receptor 3 (FGFR3) gene. Despite having no clinical features of achondroplasia, a proportion of the mother's peripheral blood leucocytes also contained the mutantFGFR3 allele. We conclude she is a germline and somatic mosaic for achondroplasia and that both children have inherited the condition from her. To our knowledge, this is the first confirmed case of germline mosaicism in achondroplasia.

Achondroplasia is the commonest form of short limbed dwarfism (birth incidence estimated at between 1:10 000 and 1:70 000)1and is transmitted as an autosomal dominant trait. As is often the case among dominant traits, a high proportion of cases are new mutations but achondroplasia is unusual in that the great majority are caused by one of two mutations at the same nucleotide in the transmembrane domain of the FGFR3 gene (G1138A transition and G1138C transversion).1 In common with otherFGFR3 mutations which cause skeletal dysplasia, the pathogenic effect of the achondroplasia mutations is thought to be altered mitogenesis and/or differentiation owing to constitutive activation of the receptor.2 There is a marked paternal age effect in achondroplasia and it has recently been shown that new mutations in achondroplasia are almost exclusively of paternal origin.3 We received peripheral blood DNA from a family with two children with achondroplasia; both parents were of normal stature. They …

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