Molecular Analysis of a Case of Thanatophoric Dysplasia Reveals Two de novo FGFR3 Missense Mutations located in cis
Journal Title: Sultan Qaboos University Medical Journal - Year 2013, Vol 13, Issue 1
Abstract
Objectives: Tanatophoric dysplasia (TD) is the most common form of lethal skeletal dysplasia. It is primarily an autosomal dominant disorder and is characterised by macrocephaly, a narrow thorax, short ribs, brachydactyly, and hypotonia. In addition to these core phenotypic features, TD type I involves micromelia with bowed femurs, while TD type II is characterised by micromelia with straight femurs and a moderate to severe clover-leaf deformity of the skull. Mutations in the FGFR3 gene are responsible for all cases of TD reported to date. Te objective of the study here was to delineate further the mutational spectrum responsible for TD. Methods: Conventional polymerase chain reaction (PCR), allele-specifc PCR, and sequence analysis were used to identify FGFR3 gene mutations in a fetus with a lethal skeletal dysplasia consistent with TD, which was detected during a routine antenatal ultrasound examination. Results: In this report we describe the identifcation of two de novo missense mutations in cis in the FGFR3 gene (p.Asn540Lys and p.Val555Met) in a fetus displaying phenotypic features consistent with TD. Conclusion: Tis is the second description of a case of TD occurring as a result of double missense FGFR3 gene mutations, suggesting that the spectrum of mutations involved in the pathogenesis of TD may be broader than previously recognised.
Authors and Affiliations
Renate Marquis-Nicholson| Diagnostic Genetics, LabPLUS, Auckland City Hospital, Auckland, New Zealand, Salim Aftimos| Genetic Health Services New Zealand – Northern Hub, Auckland City Hospital, Auckland, New Zealand, Donald R. Love| Diagnostic Genetics, LabPLUS, Auckland City Hospital, Auckland, New Zealand, School of Biological Sciences, University of Auckland, Auckland, New Zealand
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