Genetic spectrum of hereditary neuropathies with onset in the first year of life
| العنوان: | Genetic spectrum of hereditary neuropathies with onset in the first year of life |
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| المؤلفون: | Haluk Topaloglu, Els De Vriendt, Argirios Dinopoulos, Esra Battaloglu, Kim Van Hoorenbeeck, Berten Ceulemans, Vincent Timmerman, Patrick Van Bogaert, Jonathan Baets, A. Pou-Serradell, Michaela Auer-Grumbach, Albena Jordanova, Yesim Parman, Peter Van den Bergh, Ricardo E. Madrid, Andrzej Kochański, Magdalena Zimoń, Dagmara Kabzińska, K. Peeters, Laetitia Yperzeele, Geoffrey P. Miller, Gian Maria Fabrizi, Günther Bernert, Birdal Bilir, Peter De Jonghe, Ronen Spiegel, Fernand Pauly, Satu-Leena Sallinen, Tine Deconinck |
| المساهمون: | Çocuk Sağlığı ve Hastalıkları, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie |
| المصدر: | Brain, 134 (Pt 9 Brain Brain : a journal of neurology, Vol. 134, no. 9, p. 2664-2676 (2011) |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Génétique clinique, genotype-phenotype correlations, DNA Mutational Analysis, Disease, Charcot–Marie–Tooth disease, Dejerine-Sottas neuropathy, medicine.disease_cause, Bioinformatics, Cohort Studies, 0302 clinical medicine, Charcot-Marie-Tooth Disease, SH3TC2, Gene duplication, Age of Onset, Child, Genetics, 0303 health sciences, Mutation, early onset hereditary neuropathies, congenital hypomyelinating neuropathy, Dejerine–Sottas neuropathy, genotype–phenotype correlations, Middle Aged, Hypotonia, Phenotype, Child, Preschool, Hereditary Sensory and Motor Neuropathy -- genetics -- pathology -- physiopathology, medicine.symptom, Adult, Adolescent, Charcot-Marie-Tooth disease, 03 medical and health sciences, Young Adult, Neurologie, medicine, Humans, 030304 developmental biology, Aged, Genetic heterogeneity, business.industry, Infant, Original Articles, medicine.disease, Peripheral neuropathy, Charcot-Marie-Tooth Disease -- genetics -- pathology -- physiopathology, Neurology (clinical), Human medicine, Age of onset, business, Hereditary Sensory and Motor Neuropathy, 030217 neurology & neurosurgery |
| الوصف: | Early onset hereditary motor and sensory neuropathies are rare disorders encompassing congenital hypomyelinating neuropathy with disease onset in the direct post-natal period and Dejerine-Sottas neuropathy starting in infancy. The clinical spectrum, however, reaches beyond the boundaries of these two historically defined disease entities. De novo dominant mutations in PMP22, MPZ and EGR2 are known to be a typical cause of very early onset hereditary neuropathies. In addition, mutations in several other dominant and recessive genes for Charcot-Marie-Tooth disease may lead to similar phenotypes. To estimate mutation frequencies and to gain detailed insights into the genetic and phenotypic heterogeneity of early onset hereditary neuropathies, we selected a heterogeneous cohort of 77 unrelated patients who presented with symptoms of peripheral neuropathy within the first year of life. The majority of these patients were isolated in their family. We performed systematic mutation screening by means of direct sequencing of the coding regions of 11 genes: MFN2, PMP22, MPZ, EGR2, GDAP1, NEFL, FGD4, MTMR2, PRX, SBF2 and SH3TC2. In addition, screening for the Charcot-Marie-Tooth type 1A duplication on chromosome 17p11.2-12 was performed. In 35 patients (45%), mutations were identified. Mutations in MPZ, PMP22 and EGR2 were found most frequently in patients presenting with early hypotonia and breathing difficulties. The recessive genes FGD4, PRX, MTMR2, SBF2, SH3TC2 and GDAP1 were mutated in patients presenting with early foot deformities and variable delay in motor milestones after an uneventful neonatal period. Several patients displaying congenital foot deformities but an otherwise normal early development carried the Charcot-Marie-Tooth type 1A duplication. This study clearly illustrates the genetic heterogeneity underlying hereditary neuropathies with infantile onset. Journal Article Research Support, Non-U.S. Gov't SCOPUS: ar.j info:eu-repo/semantics/published |
| وصف الملف: | 2 full-text file(s): application/pdf; application/pdf; text/plain |
| اللغة: | English |
| تدمد: | 0006-8950 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a38300dcc0daaeeed746ea51631b2759Test http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/108357Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a38300dcc0daaeeed746ea51631b2759 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00068950 |
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