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ERIC Number: EJ861297
Record Type: Journal
Publication Date: 2009-Oct
Pages: 13
Abstractor: As Provided
Reference Count: 0
ISBN: N/A
ISSN: ISSN-0006-8950
Genes for Hereditary Sensory and Autonomic Neuropathies: A Genotype-Phenotype Correlation
Rotthier, Annelies; Baets, Jonathan; De Vriendt, Els; Jacobs, An; Auer-Grumbach, Michaela; Levy, Nicolas; Bonello-Palot, Nathalie; Kilic, Sara Sebnem; Weis, Joachim; Nascimento, Andres; Swinkels, Marielle; Kruyt, Moyo C.; Jordanova, Albena; De Jonghe, Peter; Timmerman, Vincent
Brain, v132 n10 p2699-2711 Oct 2009
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.
Oxford University Press. Great Clarendon Street, Oxford, OX2 6DP, UK. Tel: +44-1865-353907; Fax: +44-1865-353485; e-mail: jnls.cust.serv@oxfordjournals.org; Web site: http://brain.oxfordjournals.org/
Publication Type: Journal Articles; Reports - Research
Education Level: N/A
Audience: N/A
Language: English
Sponsor: N/A
Authoring Institution: N/A