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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Rotthier, A; Baets, J; De Vriendt, E; Jacobs, A; Auer-Grumbach, M; Lévy, N; Bonello-Palot, N; Kilic, SS; Weis, J; Nascimento, A; Swinkels, M; Kruyt, MC; Jordanova, A; De Jonghe, P; Timmerman, V.
Genes for hereditary sensory and autonomic neuropathies: a genotype-phenotype correlation.
Brain. 2009; 132(Pt 10): 2699-2711.
Doi: 10.1093/brain/awp198
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- Auer-Grumbach Michaela
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Carrier Proteins - genetics
- Chaperonin Containing TCP-1 - genetics
- Cohort Studies -
- DNA Mutational Analysis -
- Exons - genetics
- Female -
- Genetic Markers - genetics
- Genotype -
- Hereditary Sensory and Autonomic Neuropathies - genetics
- Humans -
- Intracellular Signaling Peptides and Proteins -
- Male -
- Middle Aged -
- Molecular Biology -
- Paternity -
- Phenotype -
- Protein-Serine-Threonine Kinases - genetics
- Receptor, Nerve Growth Factor - genetics
- Receptor, trkA - genetics
- Reverse Transcriptase Polymerase Chain Reaction -
- Serine C-Palmitoyltransferase - genetics
- rab GTP-Binding Proteins - genetics
- Find related publications in this database (Keywords)
- HSAN
- SPTLC1
- RAB7
- WNK1
- HSN2
- NTRK1