Genes for Hereditary Sensory and Autonomic Neuropathies: A Genotype-Phenotype Correlation

Autor/inn/en	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
Titel	Genes for Hereditary Sensory and Autonomic Neuropathies: A Genotype-Phenotype Correlation
Quelle	In: Brain, 132 (2009) 10, S.2699-2711 (13 Seiten) PDF als Volltext Verfügbarkeit
Sprache	englisch
Dokumenttyp	gedruckt; online; Zeitschriftenaufsatz
ISSN	0006-8950
DOI	10.1093/brain/awp198
Schlagwörter	Diseases; Clinical Diagnosis; Genetics; Correlation; Neurology; Pathology; Sensory Integration; Psychomotor Skills; Patients; Coding; Molecular Structure; Brain; Neurological Impairments + Suchen Sie Ihr Suchwort? Disease; Krankheit; Humangenetik; Korrelation; Neurologie; Pathologie; Sensorische Integration; Psychomotorische Aktivität; Patient; Codierung; Programmierung; Gehirn; Neurodegenerative Erkrankung
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. (As Provided).
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Erfasst von	ERIC (Education Resources Information Center), Washington, DC
Update	2017/4/10