A novel Gypsy founder mutation, p.Arg1109X in the CMT4C gene, causes variable peripheral neuropathy phenotypes
- R Gooding1,*,
- J Colomer2,*,
- R King3,
- D Angelicheva1,
- L Marns1,
- Y Parman4,
- D Chandler1,
- J Bertranpetit5,
- L Kalaydjieva1
- 1Laboratory for Molecular Genetics, Western Australian Institute for Medical Research and Centre for Medical Research, The University of Western Australia, Perth, Australia
- 2Unitat de Patologia Neuromuscular. Servei de Neurologia, Hospital Sant Joan de Déu, Barcelona, Spain
- 3University College London, Royal Free Campus, Dept. of Neurology, Rowland Hill Street, NW2 2PF London, UK
- 4Neurology Department, Istanbul Medical Faculty, Millet Cad. 34390-Capa, Istanbul, Turkey
- 5Biologia Evolutiva CEXS, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain
- Correspondence to: Professor Luba Kalaydjieva Laboratory for Molecular Genetics, Western Australian Institute for Medical Research, “B” Block, QEII Medical Centre, Hospital Avenue, Nedlands 6009, Perth, Western Australia; luba{at}cyllene.uwa.edu.au
- Received 20 April 2005
- Accepted 8 June 2005
- Revised 7 June 2005
Abstract
Background: Linkage, haplotype and sequencing analysis in a large Spanish Gypsy kindred with multiple members affected by autosomal recessive peripheral neuropathy led to the identification of a novel mutation, p.Arg1109X, in the CMT4C gene. The screening of further unrelated patients, and of a panel of ethnically matched controls, showed that p.Arg1109X is an ancestral mutation which occurs in Gypsy populations across Europe and is the most common cause of autosomal recessive Charcot–Marie–Tooth disease in Spanish Gypsies.
Objective: To report the identification of a novel Gypsy founder mutation causing autosomal recessive CMT4C disease in a sample of homozygous affected individuals.
Results: The mutation was associated with a surprisingly broad spectrum of neuropathy phenotypes, with variation in the age at onset, rate of progression, severity of muscle and sensory involvement, the presence of scoliosis, and cranial nerve involvement.
Conclusions: Ascertainment and further studies of CMT4C patients in this population will provide a unique opportunity for characterising the full range of clinical manifestations of the disease in a genetically homogeneous sample.
- CCFDN, congenital cataracts facial dysmorphism neuropathy syndrome
- CMT, Charcot–Marie–Tooth disease
- HMSNL, hereditary motor and sensory neuropathy Lom
- HMSNR, hereditary motor and sensory neuropathy Russe
Footnotes
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↵* These authors contributed equally to the work.
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Competing interests: none declared
