Genes for hereditary sensory and autonomic neuropathies: A genotype-phenotype correlation
Loading...
Date
2009-10
Authors
Rotthier, Annelies
Baets, Jonathan
Vriendt, Els De
Jacobs, An
Auer-Grumbach, Michaela
Lévy, Nicolas
Bonello-Palot, Nathalie
Weis, Joachim
Nascimento, Andrés
Swinkels, Marielle
Journal Title
Journal ISSN
Volume Title
Publisher
Oxford University
Abstract
Hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders characterized by axonal atrophy and degeneration, exclusively or predominantly affecting the sensory and autonomic neurons. So far, disease-associated mutations have been identified in seven genes: two genes for autosomal dominant (SPTLC1 and RAB7) and five genes for autosomal recessive forms of HSAN (WNK1/HSN2, NTRK1, NGFB, CCT5 and IKBKAP). We performed a systematic mutation screening of the coding sequences of six of these genes on a cohort of 100 familial and isolated patients diagnosed with HSAN. In addition, we screened the functional candidate gene NGFR (p75/NTR) encoding the nerve growth factor receptor. We identified disease-causing mutations in SPTLC1, RAB7, WNK1/HSN2 and NTRK1 in 19 patients, of which three mutations have not previously been reported. The phenotypes associated with mutations in NTRK1 and WNK1/HSN2 typically consisted of congenital insensitivity to pain and anhidrosis, and early-onset ulcero-mutilating sensory neuropathy, respectively. RAB7 mutations were only found in patients with a Charcot-Marie-Tooth type 2B (CMT2B) phenotype, an axonal sensory-motor neuropathy with pronounced ulcero-mutilations. In SPTLC1, we detected a novel mutation (S331F) corresponding to a previously unknown severe and early-onset HSAN phenotype. No mutations were found in NGFB, CCT5 and NGFR. Overall disease-associated mutations were found in 19% of the studied patient group, suggesting that additional genes are associated with HSAN. Our genotype-phenotype correlation study broadens the spectrum of HSAN and provides additional insights for molecular and clinical diagnosis.
Description
Keywords
HSAN, NTRK1, RAB7, SPTLC1, WNK1/HSN2, Trka/ngf receptor gene, Marie-tooth-disease, Nerve growth-factor, Congenital insensitivity, Anhidrosis cipa, Spastic paraplegia, Tyrosine, Kinase, Ntrk1 gene, Hsan-I, Mutation, Neurosciences & neurology
Citation
Rotthier, A. vd. (2009). "Genes for hereditary sensory and autonomic neuropathies: A genotype-phenotype correlation". Brain, 132, Part 10, 2699-271.