Rotthier, AnneliesBaets, JonathanVriendt, Els DeJacobs, AnAuer-Grumbach, MichaelaLévy, NicolasBonello-Palot, NathalieWeis, JoachimNascimento, AndrésSwinkels, MarielleKruyt, Moyo C.Jordanova, AlbenaDe Jonghe, PeterTimmerman, Vincent2022-04-222022-04-222009-10Rotthier, A. vd. (2009). "Genes for hereditary sensory and autonomic neuropathies: A genotype-phenotype correlation". Brain, 132, Part 10, 2699-271.0006-8950https://doi.org/10.1093/brain/awp198https://academic.oup.com/brain/article/132/10/2699/331429http://hdl.handle.net/11452/25985Hereditary 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.eninfo:eu-repo/semantics/openAccessHSANNTRK1RAB7SPTLC1WNK1/HSN2Trka/ngf receptor geneMarie-tooth-diseaseNerve growth-factorCongenital insensitivityAnhidrosis cipaSpastic paraplegiaTyrosineKinaseNtrk1 geneHsan-IMutationNeurosciences & neurologyArticle0002706856000182-s2.0-7034994110426992711132Part 1019651702Clinical neurologyNeurosciencesHereditary Sensory and Autonomic Neuropathies; Congenital Analgesia; 1-DeoxysphingolipidAcyltransferaseChaperoninNerve growth factor beta subunitNeurotrophin receptor p75Protein cct5Protein kinase WNK1Protein sptlc1Rab7 proteinUnclassified drugAnalgesia (sensory dysfunction)AnhidrosisArticleControlled studyFemaleGene mutationGene sequenceGenetic screeningGenotypeHereditary motor sensory neuropathyHumanMajor clinical studyMaleNucleotide sequencePhenotypePriority journal