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Your search keyword '"MESH: Abnormalities, Multiple"' showing total 2 results
Start Over Descriptor "MESH: Abnormalities, Multiple" Journal the american journal of human genetics
2 results on '"MESH: Abnormalities, Multiple"'

1. Matthew-Wood Syndrome Is Caused by Truncating Mutations in the Retinol-Binding Protein Receptor Gene STRA6

Author

Michel Vekemans, Christelle Golzio, Bettina Grattagliano-Bessières, Jelena Martinovic-Bouriel, Arnold Munnich, Sophie Delahaye, Tania Attié-Bitach, Stanislas Lyonnet, Heather C. Etchevers, Soumaya Mougou-Zrelli, Maryse Bonnière, Férechté Encha-Razavi, Sophie Thomas, IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Institut de Puériculture de Paris (IPP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Puériculture de Paris ( IPP ), and Assistance publique - Hôpitaux de Paris (AP-HP)

Subjects
Lung Diseases, MESH: Sequence Analysis, DNA, Vitamin A transport, MESH : Polymorphism, Genetic, MESH : Receptors, Cell Surface, MESH : Gene Deletion, MESH: Genetic Markers, MESH : Syndrome, MESH : Frameshift Mutation, MESH : Microphthalmos, Consanguinity, MESH: Lung Diseases, Exon, MESH : Exons, 0302 clinical medicine, Microphthalmos, MESH : Genetic Markers, MESH: Syndrome, Genetics(clinical), Frameshift Mutation, Genetics (clinical), MESH: Receptors, Cell Surface, 0303 health sciences, Fetal Growth Retardation, MESH : Lung Diseases, Homozygote, MESH: Frameshift Mutation, Exons, Syndrome, Pedigree, MESH: Membrane Proteins, MESH : Mutation, MESH: Homozygote, Genetic Markers, MESH: Abnormalities, Multiple, MESH: Mutation, MESH: Pedigree, MESH: Microphthalmos, MESH: Fetal Growth Retardation, Receptors, Cell Surface, Biology, Frameshift mutation, 03 medical and health sciences, Pulmonary hypoplasia, MESH : Homozygote, Report, MESH : Consanguinity, MESH: Polymorphism, Genetic, Genetics, medicine, Humans, Abnormalities, Multiple, MESH : Fetal Growth Retardation, MESH : Haplotypes, 030304 developmental biology, MESH: Consanguinity, MESH : Mutagenesis, Insertional, Polymorphism, Genetic, MESH: Humans, Anophthalmia, MESH : Abnormalities, Multiple, Genetic heterogeneity, MESH : Humans, Pulmonary Agenesis, Membrane Proteins, Sequence Analysis, DNA, MESH: Haplotypes, medicine.disease, Molecular biology, Mutagenesis, Insertional, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Haplotypes, MESH: Mutagenesis, Insertional, MESH : Membrane Proteins, MESH: Gene Deletion, MESH : Pedigree, [ SDV.BDD.EO ] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Mutation, MESH: Exons, Matthew Wood syndrome, Gene Deletion, 030217 neurology & neurosurgery, MESH : Sequence Analysis, DNA
Abstract

International audience; Retinoic acid (RA) is a potent teratogen in all vertebrates when tight homeostatic controls on its endogenous dose, location, or timing are perturbed during early embryogenesis. STRA6 encodes an integral cell-membrane protein that favors RA uptake from soluble retinol-binding protein; its transcription is directly regulated by RA levels. Molecular analysis of STRA6 was undertaken in two human fetuses from consanguineous families we previously described with Matthew-Wood syndrome in a context of severe microphthalmia, pulmonary agenesis, bilateral diaphragmatic eventration, duodenal stenosis, pancreatic malformations, and intrauterine growth retardation. The fetuses had either a homozygous insertion/deletion in exon 2 or a homozygous insertion in exon 7 predicting a premature stop codon in STRA6 transcripts. Five other fetuses presenting at least one of the two major signs of clinical anophthalmia or pulmonary hypoplasia with at least one of the two associated signs of diaphragmatic closure defect or cardiopathy had no STRA6 mutations. These findings suggest a molecular basis for the prenatal manifestations of Matthew-Wood syndrome and suggest that phenotypic overlap with other associations may be due to genetic heterogeneity of elements common to the RA- and fibroblast growth factor-signaling cascades.

Published
2007

2. Distinct effects of allelic NFIX mutations on nonsense-mediated mRNA decay engender either a sotos-like or a Marshall-Smith syndrome

Author

MALAN, Valérie, Rajan, Diana, Thomas, Sophie, Shaw, Adam, Louis dit Picard, Hélène, Layet, Valérie, Till, Marianne, Van Haeringen, Arie, Mortier, Geert, Nampoothiri, Sheela, Puseljić, Silvija, Legeai-Mallet, Laurence, Carter, Nigel, Vekemans, Michel, Munnich, Arnold, Hennekam, Raoul, Colleaux, Laurence, Cormier-Daire, Valérie, Pušeljić, Silvija, Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Cytogénétique et Génétique Médicale, Groupe Hospitalier du Havre-Hôpital Gustave Flaubert, Service de cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, Department of Clinical Genetics, Leiden University Medical Centre, Department of Medical Genetics, Antwerp University Hospital [Edegem] (UZA), Amrita Institute of Medical Sciences and Research Center, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Clinical Genetics, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Imagine - Institut des maladies génétiques (IMAGINE - U1163), CHU Cochin [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, and Paediatrics

Subjects
Male, Candidate gene, MESH: Chromosomes, Human, Pair 19, RNA Stability, Nonsense-mediated decay, DNA Mutational Analysis, MESH: Base Sequence, MESH: NFI Transcription Factors, Marshall–Smith syndrome, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Child, Genetics(clinical), MESH: Syndrome, MESH: Codon, Nonsense, MESH: DNA Mutational Analysis, Child, Genetics (clinical), In Situ Hybridization, Genetics, 0303 health sciences, Comparative Genomic Hybridization, biology, MESH: Genetic Testing, Reverse Transcriptase Polymerase Chain Reaction, 030305 genetics & heredity, MESH: RNA Stability, Syndrome, NFIX, MESH: Gene Expression Regulation, 3. Good health, Codon, Nonsense, Female, medicine.symptom, Adult, MESH: Abnormalities, Multiple, MESH: Mutation, Adolescent, Nonsense mutation, Molecular Sequence Data, Article, Frameshift mutation, 03 medical and health sciences, MESH: In Situ Hybridization, medicine, Humans, Abnormalities, Multiple, Genetic Testing, RNA, Messenger, Alleles, 030304 developmental biology, MESH: RNA, Messenger, MESH: Adolescent, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, MESH: Alleles, Macrocephaly, MESH: Adult, medicine.disease, MESH: Male, MESH: Comparative Genomic Hybridization, NFI Transcription Factors, Gene Expression Regulation, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Overgrowth syndrome, Mutation, biology.protein, Human medicine, Chromosomes, Human, Pair 19, MESH: Female
Abstract

International audience; By using a combination of array comparative genomic hybridization and a candidate gene approach, we identified nuclear factor I/X (NFIX) deletions or nonsense mutation in three sporadic cases of a Sotos-like overgrowth syndrome with advanced bone age, macrocephaly, developmental delay, scoliosis, and unusual facies. Unlike the aforementioned human syndrome, Nfix-deficient mice are unable to gain weight and die in the first 3 postnatal weeks, while they also present with a spinal deformation and decreased bone mineralization. These features prompted us to consider NFIX as a candidate gene for Marshall-Smith syndrome (MSS), a severe malformation syndrome characterized by failure to thrive, respiratory insufficiency, accelerated osseous maturation, kyphoscoliosis, osteopenia, and unusual facies. Distinct frameshift and splice NFIX mutations that escaped nonsense-mediated mRNA decay (NMD) were identified in nine MSS subjects. NFIX belongs to the Nuclear factor one (NFI) family of transcription factors, but its specific function is presently unknown. We demonstrate that NFIX is normally expressed prenatally during human brain development and skeletogenesis. These findings demonstrate that allelic NFIX mutations trigger distinct phenotypes, depending specifically on their impact on NMD.

Published
2010

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