LARP7 variants and further delineation of the Alazami syndrome phenotypic spectrum among primordial dwarfisms: 2 sisters |
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Authors: | Marion Imbert-Bouteille Frédéric Tran Mau Them Julien Thevenon Thomas Guignard Vincent Gatinois Jean-Baptiste Riviere Anne Boland Vincent Meyer Jean-François Deleuze Elodie Sanchez Florence Apparailly David Geneviève Marjolaine Willems |
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Institution: | 1. Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée, Centre de Référence Anomalies du développement et Syndromes Malformatifs, Plateforme Recherche de Microremaniements Chromosomiques, CHU de Montpellier, Université de Montpellier, France;2. Unité Inserm, U1183, Hôpital Saint-Eloi, CHU de Montpellier, Montpellier, France;3. Equipe Génétique des Anomalies du Développement, INSERM UMR1231, Université de Bourgogne-Franche Comté, France;4. Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, Hôpital d’Enfants, CHU Dijon et Université de Bourgogne, France;5. Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie - CHU Dijon, Dijon, France;6. Centre National de Génotypage, Institut de Génomique, Commissariat à l’Energie Atomique, Evry, France;7. Centre de Génétique, Hôpital Couple-Enfant, CHU Grenoble-Alpes, La Tronche, France |
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Abstract: | Alazami syndrome (AS) (MIM# 615071) is an autosomal recessive microcephalic primordial dwarfism (PD) with recognizable facial features and severe intellectual disability due to depletion or loss of function variants in LARP7. To date, 15 patients with AS have been reported. Here we describe two consanguineous Algerian sisters with Alazami PD due to LARP7 homozygous pathogenic variants detected by whole exome sequencing. By comparing these two additional cases with those previously reported, we strengthen the key features of AS: severe growth restriction, severe intellectual disability and some distinguishing facial features such as broad nose, malar hypoplasia, wide mouth, full lips and abnormally set teeth. We also report significant new findings enabling further delineation of this syndrome: disproportionately mild microcephaly, stereotypic hand wringing and severe anxiety, thickened skin over the hands and feet, and skeletal, eye and heart malformations. From previous reviews, we summarize the main etiologies of PD according to the involved mechanisms and cellular pathways, highlighting their clinical core features. |
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Keywords: | Alazami syndrome Primordial dwarfism LARP7 Intellectual disability |
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