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Your search keyword '"Genotype first"' showing total 4 results
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4 results on '"Genotype first"'

1. The diagnostic rate of inherited metabolic disorders by exome sequencing in a cohort of 547 individuals with developmental disorders

Author

Julian Delanne, Ange-Line Bruel, Frédéric Huet, Sébastien Moutton, Sophie Nambot, Margot Grisval, Nada Houcinat, Paul Kuentz, Arthur Sorlin, Patrick Callier, Nolwenn Jean-Marcais, Anne-Laure Mosca-Boidron, Frédéric Tran Mau-Them, Anne-Sophie Denommé-Pichon, Antonio Vitobello, Daphné Lehalle, Salima El Chehadeh, Christine Francannet, Marine Lebrun, Laetitia Lambert, Marie-Line Jacquemont, Marion Gerard-Blanluet, Jean-Luc Alessandri, Marjolaine Willems, Julien Thevenon, Mondher Chouchane, Véronique Darmency, Clémence Fatus-Fauconnier, Sébastien Gay, Marie Bournez, Alice Masurel, Vanessa Leguy, Yannis Duffourd, Christophe Philippe, François Feillet, Laurence Faivre, and Christel Thauvin-Robinet

Subjects
Inherited metabolic disorders, Exome sequencing, Intellectual disability, Developmental delay, Genotype first, Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

Considering that some Inherited Metabolic Disorders (IMDs) can be diagnosed in patients with no distinctive clinical features of IMDs, we aimed to evaluate the power of exome sequencing (ES) to diagnose IMDs within a cohort of 547 patients with unspecific developmental disorders (DD). IMDs were diagnosed in 12% of individuals with causative diagnosis (177/547). There are clear benefits of using ES in DD to diagnose IMD, particularly in cases where biochemical studies are unavailable. Synopsis: Exome sequencing and diagnostic rate of Inherited Metabolic Disorders in individuals with developmental disorders.

Published
2021
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2. De novo microdeletions and point mutations affecting SOX2 in three individuals with intellectual disability but without major eye malformations.

Author

Dennert, Nicola, Engels, Hartmut, Cremer, Kirsten, Becker, Jessica, Wohlleber, Eva, Albrecht, Beate, Ehret, Julia K., Lüdecke, Hermann‐Josef, Suri, Mohnish, Carignani, Giulia, Renieri, Alessandra, Kukuk, Guido M., Wieland, Thomas, Andrieux, Joris, Strom, Tim M., Wieczorek, Dagmar, Dieux‐Coëslier, Anne, and Zink, Alexander M.

Abstract

Loss-of-function mutations and deletions of the SOX2 gene are known to cause uni- and bilateral anophthalmia and microphthalmia as well as related disorders such as anophthalmia-esophageal-genital syndrome. Thus, anophthalmia/microphthalmia is the primary indication for targeted, 'phenotype first' analyses of SOX2. However, SOX2 mutations are also associated with a wide range of non-ocular abnormalities, such as postnatal growth retardation, structural brain anomalies, hypogenitalism, and developmental delay. The present report describes three patients without anophthalmia/microphthalmia and loss-of-function mutations or microdeletions of SOX2 who had been investigated in a 'genotype first' manner due to intellectual disability/developmental delay using whole exome sequencing or chromosomal microarray analyses. This result prompted us to perform SOX2 Sanger sequencing in 192 developmental delay/intellectual disability patients without anophthalmia or microphthalmia. No additional SOX2 loss-of-function mutations were detected in this cohort, showing that SOX2 is clearly not a major cause of intellectual disability without anophthalmia/microphthalmia. In our three patients and four further, reported 'genotype first' SOX2 microdeletion patients, anophthalmia/microphthalmia was present in less than half of the patients. Thus, SOX2 is another example of a gene whose clinical spectrum is broadened by the generation of 'genotype first' findings using hypothesis-free, genome-wide methods. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
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3. The diagnostic rate of inherited metabolic disorders by exome sequencing in a cohort of 547 individuals with developmental disorders.

Author

Delanne J, Bruel AL, Huet F, Moutton S, Nambot S, Grisval M, Houcinat N, Kuentz P, Sorlin A, Callier P, Jean-Marcais N, Mosca-Boidron AL, Mau-Them FT, Denommé-Pichon AS, Vitobello A, Lehalle D, El Chehadeh S, Francannet C, Lebrun M, Lambert L, Jacquemont ML, Gerard-Blanluet M, Alessandri JL, Willems M, Thevenon J, Chouchane M, Darmency V, Fatus-Fauconnier C, Gay S, Bournez M, Masurel A, Leguy V, Duffourd Y, Philippe C, Feillet F, Faivre L, and Thauvin-Robinet C

Abstract

Considering that some Inherited Metabolic Disorders (IMDs) can be diagnosed in patients with no distinctive clinical features of IMDs, we aimed to evaluate the power of exome sequencing (ES) to diagnose IMDs within a cohort of 547 patients with unspecific developmental disorders (DD). IMDs were diagnosed in 12% of individuals with causative diagnosis (177/547). There are clear benefits of using ES in DD to diagnose IMD, particularly in cases where biochemical studies are unavailable., Synopsis: Exome sequencing and diagnostic rate of Inherited Metabolic Disorders in individuals with developmental disorders., Competing Interests: The authors declare no conflicts of interest., (© 2021 Published by Elsevier Inc.)

Published
2021
Full Text
View/download PDF

4. De novo microdeletions and point mutations affecting SOX2 in three individuals with intellectual disability but without major eye malformations

Author

Thomas Wieland, Guido M. Kukuk, Dagmar Wieczorek, Anne Dieux-Coeslier, Alessandra Renieri, Jessica Becker, Tim M. Strom, Julia K. Ehret, Beate Albrecht, Mohnish Suri, Kirsten Cremer, Alexander M. Zink, Joris Andrieux, Nicola Dennert, Giulia Carignani, Hermann-Josef Lüdecke, Hartmut Engels, and Eva Wohlleber

Subjects
Male, 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Medizin, SOX2, 030105 genetics & heredity, Biology, Polymorphism, Single Nucleotide, Microphthalmia, genotype first, intellectual disability, microdeletion, whole exome sequencing, Genetics, Genetics (clinical), 03 medical and health sciences, symbols.namesake, Intellectual disability, Genotype, medicine, Humans, Point Mutation, Exome, Eye Abnormalities, Registries, Genetic Association Studies, Exome sequencing, Sequence Deletion, Sanger sequencing, Comparative Genomic Hybridization, Anophthalmia, SOXB1 Transcription Factors, Infant, Newborn, Brain, Facies, High-Throughput Nucleotide Sequencing, medicine.disease, Magnetic Resonance Imaging, eye diseases, Phenotype, Child, Preschool, symbols, Female, sense organs, Comparative genomic hybridization
Abstract

Loss-of-function mutations and deletions of the SOX2 gene are known to cause uni- and bilateral anophthalmia and microphthalmia as well as related disorders such as anophthalmia-esophageal-genital syndrome. Thus, anophthalmia/microphthalmia is the primary indication for targeted, "phenotype first" analyses of SOX2. However, SOX2 mutations are also associated with a wide range of non-ocular abnormalities, such as postnatal growth retardation, structural brain anomalies, hypogenitalism, and developmental delay. The present report describes three patients without anophthalmia/microphthalmia and loss-of-function mutations or microdeletions of SOX2 who had been investigated in a "genotype first" manner due to intellectual disability/developmental delay using whole exome sequencing or chromosomal microarray analyses. This result prompted us to perform SOX2 Sanger sequencing in 192 developmental delay/intellectual disability patients without anophthalmia or microphthalmia. No additional SOX2 loss-of-function mutations were detected in this cohort, showing that SOX2 is clearly not a major cause of intellectual disability without anophthalmia/microphthalmia. In our three patients and four further, reported "genotype first" SOX2 microdeletion patients, anophthalmia/microphthalmia was present in less than half of the patients. Thus, SOX2 is another example of a gene whose clinical spectrum is broadened by the generation of "genotype first" findings using hypothesis-free, genome-wide methods. © 2016 Wiley Periodicals, Inc.

Published
2017

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