One <i>NF1</i> Mutation may Conceal Another
Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with complete penetrance but high variable expressivity. NF1 is caused by loss-of-function mutations in the <i>NF1</i> gene, a negative regulator of the RAS-MAPK pathway. The <i>NF1</i> gene has one of the highes...
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Format: | Article |
Language: | English |
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MDPI AG
2019-08-01
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Series: | Genes |
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Online Access: | https://www.mdpi.com/2073-4425/10/9/633 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Laurence Pacot Cyril Burin des Roziers Ingrid Laurendeau Audrey Briand-Suleau Audrey Coustier Théodora Mayard Camille Tlemsani Laurence Faivre Quentin Thomas Diana Rodriguez Sophie Blesson Hélène Dollfus Yvon-Gauthier Muller Béatrice Parfait Michel Vidaud Brigitte Gilbert-Dussardier Catherine Yardin Benjamin Dauriat Christian Derancourt Dominique Vidaud Eric Pasmant |
spellingShingle |
Laurence Pacot Cyril Burin des Roziers Ingrid Laurendeau Audrey Briand-Suleau Audrey Coustier Théodora Mayard Camille Tlemsani Laurence Faivre Quentin Thomas Diana Rodriguez Sophie Blesson Hélène Dollfus Yvon-Gauthier Muller Béatrice Parfait Michel Vidaud Brigitte Gilbert-Dussardier Catherine Yardin Benjamin Dauriat Christian Derancourt Dominique Vidaud Eric Pasmant One <i>NF1</i> Mutation may Conceal Another Genes de novo variant Legius syndrome neurofibromatosis type 1 <i>NF1</i> <i>SPRED1</i> |
author_facet |
Laurence Pacot Cyril Burin des Roziers Ingrid Laurendeau Audrey Briand-Suleau Audrey Coustier Théodora Mayard Camille Tlemsani Laurence Faivre Quentin Thomas Diana Rodriguez Sophie Blesson Hélène Dollfus Yvon-Gauthier Muller Béatrice Parfait Michel Vidaud Brigitte Gilbert-Dussardier Catherine Yardin Benjamin Dauriat Christian Derancourt Dominique Vidaud Eric Pasmant |
author_sort |
Laurence Pacot |
title |
One <i>NF1</i> Mutation may Conceal Another |
title_short |
One <i>NF1</i> Mutation may Conceal Another |
title_full |
One <i>NF1</i> Mutation may Conceal Another |
title_fullStr |
One <i>NF1</i> Mutation may Conceal Another |
title_full_unstemmed |
One <i>NF1</i> Mutation may Conceal Another |
title_sort |
one <i>nf1</i> mutation may conceal another |
publisher |
MDPI AG |
series |
Genes |
issn |
2073-4425 |
publishDate |
2019-08-01 |
description |
Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with complete penetrance but high variable expressivity. NF1 is caused by loss-of-function mutations in the <i>NF1</i> gene, a negative regulator of the RAS-MAPK pathway. The <i>NF1</i> gene has one of the highest mutation rates in human disorders, which may explain the outbreak of independent de novo variants in the same family. Here, we report the co-occurrence of pathogenic variants in the <i>NF1</i> and <i>SPRED1</i> genes in six families with NF1 and Legius syndrome, using next-generation sequencing. In five of these families, we observed the co-occurrence of two independent <i>NF1</i> variants. All <i>NF1</i> variants were classified as pathogenic, according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines. In the sixth family, one sibling inherited a complete deletion of the <i>NF1</i> gene from her mother and carried a variant of unknown significance in the <i>SPRED1</i> gene. This variant was also present in her brother, who was diagnosed with Legius syndrome, a differential diagnosis of NF1. This work illustrates the complexity of molecular diagnosis in a not-so-rare genetic disease. |
topic |
de novo variant Legius syndrome neurofibromatosis type 1 <i>NF1</i> <i>SPRED1</i> |
url |
https://www.mdpi.com/2073-4425/10/9/633 |
work_keys_str_mv |
AT laurencepacot oneinf1imutationmayconcealanother AT cyrilburindesroziers oneinf1imutationmayconcealanother AT ingridlaurendeau oneinf1imutationmayconcealanother AT audreybriandsuleau oneinf1imutationmayconcealanother AT audreycoustier oneinf1imutationmayconcealanother AT theodoramayard oneinf1imutationmayconcealanother AT camilletlemsani oneinf1imutationmayconcealanother AT laurencefaivre oneinf1imutationmayconcealanother AT quentinthomas oneinf1imutationmayconcealanother AT dianarodriguez oneinf1imutationmayconcealanother AT sophieblesson oneinf1imutationmayconcealanother AT helenedollfus oneinf1imutationmayconcealanother AT yvongauthiermuller oneinf1imutationmayconcealanother AT beatriceparfait oneinf1imutationmayconcealanother AT michelvidaud oneinf1imutationmayconcealanother AT brigittegilbertdussardier oneinf1imutationmayconcealanother AT catherineyardin oneinf1imutationmayconcealanother AT benjamindauriat oneinf1imutationmayconcealanother AT christianderancourt oneinf1imutationmayconcealanother AT dominiquevidaud oneinf1imutationmayconcealanother AT ericpasmant oneinf1imutationmayconcealanother |
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spelling |
doaj-ce9a3886345e4722af2f94fbdd2d87b62020-11-25T01:12:22ZengMDPI AGGenes2073-44252019-08-0110963310.3390/genes10090633genes10090633One <i>NF1</i> Mutation may Conceal AnotherLaurence Pacot0Cyril Burin des Roziers1Ingrid Laurendeau2Audrey Briand-Suleau3Audrey Coustier4Théodora Mayard5Camille Tlemsani6Laurence Faivre7Quentin Thomas8Diana Rodriguez9Sophie Blesson10Hélène Dollfus11Yvon-Gauthier Muller12Béatrice Parfait13Michel Vidaud14Brigitte Gilbert-Dussardier15Catherine Yardin16Benjamin Dauriat17Christian Derancourt18Dominique Vidaud19Eric Pasmant20Service de Génétique et Biologie Moléculaires, Hôpital Cochin, HUPC, Assistance Publique-Hôpitaux de Paris, 75014 Paris, FranceService de Génétique et Biologie Moléculaires, Hôpital Cochin, HUPC, Assistance Publique-Hôpitaux de Paris, 75014 Paris, FranceInstitut Cochin, INSERM U1016, Université Paris Descartes, 75014 Paris, FranceService de Génétique et Biologie Moléculaires, Hôpital Cochin, HUPC, Assistance Publique-Hôpitaux de Paris, 75014 Paris, FranceService de Génétique et Biologie Moléculaires, Hôpital Cochin, HUPC, Assistance Publique-Hôpitaux de Paris, 75014 Paris, FranceService de Génétique et Biologie Moléculaires, Hôpital Cochin, HUPC, Assistance Publique-Hôpitaux de Paris, 75014 Paris, FranceService de Génétique et Biologie Moléculaires, Hôpital Cochin, HUPC, Assistance Publique-Hôpitaux de Paris, 75014 Paris, FranceInserm, UMR 1231, Génétique des Anomalies du Développement, Université de Bourgogne, 21079 Dijon, FranceInserm, UMR 1231, Génétique des Anomalies du Développement, Université de Bourgogne, 21079 Dijon, FranceDepartment of Child Neurology and National Reference Center for Neurogenetic Disorders, Armand Trousseau Hospital, GHUEP, AP-HP, INSERM U1141, 75012 Paris, FranceService de Génétique, CHRU de Tours, 37044 Tours, FranceCentre de référence pour les Affections Rares en Génétique Ophtalmologique (CARGO), Hôpital Civil, 67091 Strasbourg, FranceService de Génétique Médicale, Hôpital de Hautepierre, 67200 Strasbourg, FranceService de Génétique et Biologie Moléculaires, Hôpital Cochin, HUPC, Assistance Publique-Hôpitaux de Paris, 75014 Paris, FranceService de Génétique et Biologie Moléculaires, Hôpital Cochin, HUPC, Assistance Publique-Hôpitaux de Paris, 75014 Paris, FranceService de Génétique, EA3808, Université de Poitiers, CHU de Poitiers, 86000 Poitiers, FranceDepartment of Cytogenetics and clinical genetics, Limoges University Hospital, 87042 Limoges, FranceDepartment of Cytogenetics and clinical genetics, Limoges University Hospital, 87042 Limoges, FranceEA 4537, Antilles University, 97261 Fort-de-France, Martinique, FranceService de Génétique et Biologie Moléculaires, Hôpital Cochin, HUPC, Assistance Publique-Hôpitaux de Paris, 75014 Paris, FranceService de Génétique et Biologie Moléculaires, Hôpital Cochin, HUPC, Assistance Publique-Hôpitaux de Paris, 75014 Paris, FranceNeurofibromatosis type 1 (NF1) is an autosomal dominant disease with complete penetrance but high variable expressivity. NF1 is caused by loss-of-function mutations in the <i>NF1</i> gene, a negative regulator of the RAS-MAPK pathway. The <i>NF1</i> gene has one of the highest mutation rates in human disorders, which may explain the outbreak of independent de novo variants in the same family. Here, we report the co-occurrence of pathogenic variants in the <i>NF1</i> and <i>SPRED1</i> genes in six families with NF1 and Legius syndrome, using next-generation sequencing. In five of these families, we observed the co-occurrence of two independent <i>NF1</i> variants. All <i>NF1</i> variants were classified as pathogenic, according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines. In the sixth family, one sibling inherited a complete deletion of the <i>NF1</i> gene from her mother and carried a variant of unknown significance in the <i>SPRED1</i> gene. This variant was also present in her brother, who was diagnosed with Legius syndrome, a differential diagnosis of NF1. This work illustrates the complexity of molecular diagnosis in a not-so-rare genetic disease.https://www.mdpi.com/2073-4425/10/9/633de novo variantLegius syndromeneurofibromatosis type 1<i>NF1</i><i>SPRED1</i> |