The Experts below are selected from a list of 423 Experts worldwide ranked by ideXlab platform
Jorge Sequeiros - One of the best experts on this subject based on the ideXlab platform.
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two pairs of proven monozygotic twins discordant for Familial Amyloid Neuropathy fap ttr met 30
Journal of Medical Genetics, 1999Co-Authors: Miguel Munarques, Jorge L Pedrosa, Teresa Coelho, Leonor Gusmao, Raquel Seruca, A Amorim, Jorge SequeirosAbstract:Twin studies are an important tool in medical genetics for the evaluation of the relative roles of genetic and non-genetic factors in several diseases. Familial Amyloidotic polyNeuropathy type I (FAP-I), TTR Met 30, was present in two sets of proven monozygotic (MZ) twins, one from Majorca and the other from Portugal. Monozygosity was established by analysis of DNA polymorphisms. Both pairs were discordant for age at onset and some clinical manifestations of FAP-I. We reviewed the diVerences in age at onset and clinical features in both sets and in two other pairs of presumed MZ twins with FAP-I and compared them with those in MZ twin pairs with other Mendelian disorders, such as neurofibromatosis type 1, Huntington’s disease, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. We conclude that, in addition to the postulated modifying genes, there must be a significant contribution from non-genetic factors to the phenotypic variability of FAP-I (age at onset and clinical expression), either because of enviromental diVerences or stochastic events during (or after) the twinning process. (J Med Genet 1999;36:629‐632)
Konstanze Hörtnagel - One of the best experts on this subject based on the ideXlab platform.
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Frequent genes in rare diseases: panel-based next generation sequencing to disclose causal mutations in hereditary neuropathies.
Journal of Neurochemistry, 2017Co-Authors: M.f. Dohrn, Julia Mohr, Nicola Glöckle, Lejla Mulahasanovic, Corina Heller, Bauer C, E. Riesch, Becker A, Florian Battke, Konstanze HörtnagelAbstract:Hereditary neuropathies comprise a wide variety of chronic diseases associated to more than 80 genes identified to date. We herein examined 612 index patients with either a Charcot-Marie-Tooth phenotype, hereditary sensory Neuropathy, Familial Amyloid Neuropathy, or small fiber Neuropathy using a customized multigene panel based on the next generation sequencing technique. In 121 cases (19.8%), we identified at least one putative pathogenic mutation. Of these, 54.4% showed an autosomal dominant, 33.9% an autosomal recessive, and 11.6% an X-linked inheritance. The most frequently affected genes were PMP22 (16.4%), GJB1 (10.7%), MPZ, and SH3TC2 (both 9.9%), and MFN2 (8.3%). We further detected likely or known pathogenic variants in HINT1, HSPB1, NEFL, PRX, IGHMBP2, NDRG1, TTR, EGR2, FIG4, GDAP1, LMNA, LRSAM1, POLG, TRPV4, AARS, BIC2, DHTKD1, FGD4, HK1, INF2, KIF5A, PDK3, REEP1, SBF1, SBF2, SCN9A, and SPTLC2 with a declining frequency. Thirty-four novel variants were considered likely pathogenic not having previously been described in association with any disorder in the literature. In one patient, two homozygous mutations in HK1 were detected in the multigene panel, but not by whole exome sequencing. A novel missense mutation in KIF5A was considered pathogenic because of the highly compatible phenotype. In one patient, the plasma sphingolipid profile could functionally prove the pathogenicity of a mutation in SPTLC2. One pathogenic mutation in MPZ was identified after being previously missed by Sanger sequencing. We conclude that panel based next generation sequencing is a useful, time- and cost-effective approach to assist clinicians in identifying the correct diagnosis and enable causative treatment considerations.
Miguel Munarques - One of the best experts on this subject based on the ideXlab platform.
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two pairs of proven monozygotic twins discordant for Familial Amyloid Neuropathy fap ttr met 30
Journal of Medical Genetics, 1999Co-Authors: Miguel Munarques, Jorge L Pedrosa, Teresa Coelho, Leonor Gusmao, Raquel Seruca, A Amorim, Jorge SequeirosAbstract:Twin studies are an important tool in medical genetics for the evaluation of the relative roles of genetic and non-genetic factors in several diseases. Familial Amyloidotic polyNeuropathy type I (FAP-I), TTR Met 30, was present in two sets of proven monozygotic (MZ) twins, one from Majorca and the other from Portugal. Monozygosity was established by analysis of DNA polymorphisms. Both pairs were discordant for age at onset and some clinical manifestations of FAP-I. We reviewed the diVerences in age at onset and clinical features in both sets and in two other pairs of presumed MZ twins with FAP-I and compared them with those in MZ twin pairs with other Mendelian disorders, such as neurofibromatosis type 1, Huntington’s disease, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. We conclude that, in addition to the postulated modifying genes, there must be a significant contribution from non-genetic factors to the phenotypic variability of FAP-I (age at onset and clinical expression), either because of enviromental diVerences or stochastic events during (or after) the twinning process. (J Med Genet 1999;36:629‐632)
Vlastimil Scudla - One of the best experts on this subject based on the ideXlab platform.
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val50ala variant of Familial Amyloid Neuropathy a rare case in the czech republic
Orphanet Journal of Rare Diseases, 2015Co-Authors: Tomas Pika, Pavla Latalova, Helena Hulkova, Patrik Flodr, Vladimir Mejzlik, Vlastimil ScudlaAbstract:Background Hereditary Amyloidosis represents approximately 4% of the total cases of Amyloidoses. The most frequent Familial type is caused by deposition of mutated transthyretin (TTR, prealbumin). So far it has been identified more than 100 mutations in the transthyretin gene and type of causal mutation is also characterized by a clinical picture of the disease. The most common variant is a neuropathic disease. Characteristic feature is an endemic occurrence with very low incidence in the Central Europe countries.
M.f. Dohrn - One of the best experts on this subject based on the ideXlab platform.
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Frequent genes in rare diseases: panel-based next generation sequencing to disclose causal mutations in hereditary neuropathies.
Journal of Neurochemistry, 2017Co-Authors: M.f. Dohrn, Julia Mohr, Nicola Glöckle, Lejla Mulahasanovic, Corina Heller, Bauer C, E. Riesch, Becker A, Florian Battke, Konstanze HörtnagelAbstract:Hereditary neuropathies comprise a wide variety of chronic diseases associated to more than 80 genes identified to date. We herein examined 612 index patients with either a Charcot-Marie-Tooth phenotype, hereditary sensory Neuropathy, Familial Amyloid Neuropathy, or small fiber Neuropathy using a customized multigene panel based on the next generation sequencing technique. In 121 cases (19.8%), we identified at least one putative pathogenic mutation. Of these, 54.4% showed an autosomal dominant, 33.9% an autosomal recessive, and 11.6% an X-linked inheritance. The most frequently affected genes were PMP22 (16.4%), GJB1 (10.7%), MPZ, and SH3TC2 (both 9.9%), and MFN2 (8.3%). We further detected likely or known pathogenic variants in HINT1, HSPB1, NEFL, PRX, IGHMBP2, NDRG1, TTR, EGR2, FIG4, GDAP1, LMNA, LRSAM1, POLG, TRPV4, AARS, BIC2, DHTKD1, FGD4, HK1, INF2, KIF5A, PDK3, REEP1, SBF1, SBF2, SCN9A, and SPTLC2 with a declining frequency. Thirty-four novel variants were considered likely pathogenic not having previously been described in association with any disorder in the literature. In one patient, two homozygous mutations in HK1 were detected in the multigene panel, but not by whole exome sequencing. A novel missense mutation in KIF5A was considered pathogenic because of the highly compatible phenotype. In one patient, the plasma sphingolipid profile could functionally prove the pathogenicity of a mutation in SPTLC2. One pathogenic mutation in MPZ was identified after being previously missed by Sanger sequencing. We conclude that panel based next generation sequencing is a useful, time- and cost-effective approach to assist clinicians in identifying the correct diagnosis and enable causative treatment considerations.