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Genetic spectrum of hereditary neuropathies with onset in the first year of life.
Brain. 2011 Sep; 134(Pt 9):2664-76.B

Abstract

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.

Authors+Show Affiliations

Neurogenetics Group, VIB Department of Molecular Genetics, University of Antwerp, Universiteitsplein 1, B-2610 Antwerpen, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21840889

Citation

Baets, Jonathan, et al. "Genetic Spectrum of Hereditary Neuropathies With Onset in the First Year of Life." Brain : a Journal of Neurology, vol. 134, no. Pt 9, 2011, pp. 2664-76.
Baets J, Deconinck T, De Vriendt E, et al. Genetic spectrum of hereditary neuropathies with onset in the first year of life. Brain. 2011;134(Pt 9):2664-76.
Baets, J., Deconinck, T., De Vriendt, E., Zimoń, M., Yperzeele, L., Van Hoorenbeeck, K., Peeters, K., Spiegel, R., Parman, Y., Ceulemans, B., Van Bogaert, P., Pou-Serradell, A., Bernert, G., Dinopoulos, A., Auer-Grumbach, M., Sallinen, S. L., Fabrizi, G. M., Pauly, F., Van den Bergh, P., ... De Jonghe, P. (2011). Genetic spectrum of hereditary neuropathies with onset in the first year of life. Brain : a Journal of Neurology, 134(Pt 9), 2664-76. https://doi.org/10.1093/brain/awr184
Baets J, et al. Genetic Spectrum of Hereditary Neuropathies With Onset in the First Year of Life. Brain. 2011;134(Pt 9):2664-76. PubMed PMID: 21840889.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic spectrum of hereditary neuropathies with onset in the first year of life. AU - Baets,Jonathan, AU - Deconinck,Tine, AU - De Vriendt,Els, AU - Zimoń,Magdalena, AU - Yperzeele,Laetitia, AU - Van Hoorenbeeck,Kim, AU - Peeters,Kristien, AU - Spiegel,Ronen, AU - Parman,Yesim, AU - Ceulemans,Berten, AU - Van Bogaert,Patrick, AU - Pou-Serradell,Adolf, AU - Bernert,Günther, AU - Dinopoulos,Argirios, AU - Auer-Grumbach,Michaela, AU - Sallinen,Satu-Leena, AU - Fabrizi,Gian Maria, AU - Pauly,Fernand, AU - Van den Bergh,Peter, AU - Bilir,Birdal, AU - Battaloglu,Esra, AU - Madrid,Ricardo E, AU - Kabzińska,Dagmara, AU - Kochanski,Andrzej, AU - Topaloglu,Haluk, AU - Miller,Geoffrey, AU - Jordanova,Albena, AU - Timmerman,Vincent, AU - De Jonghe,Peter, Y1 - 2011/08/11/ PY - 2011/8/16/entrez PY - 2011/8/16/pubmed PY - 2011/11/9/medline SP - 2664 EP - 76 JF - Brain : a journal of neurology JO - Brain VL - 134 IS - Pt 9 N2 - 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. SN - 1460-2156 UR - https://www.unboundmedicine.com/medline/citation/21840889/Genetic_spectrum_of_hereditary_neuropathies_with_onset_in_the_first_year_of_life_ L2 - https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/awr184 DB - PRIME DP - Unbound Medicine ER -