Two Monogenetic Disorders, Activated PI3-Kinase-δ Syndrome 2 and Smith–Magenis Syndrome, in One Patient: Case Report and a Literature Review of Neurodevelopmental Impact in Primary Immunodeficiencies Associated With Disturbed PI3K Signaling
Activated PI3-kinase-δ syndrome 2 (APDS2) is caused by autosomal dominant mutations in the PIK3R1 gene encoding the p85α, p55α, and p50α regulatory subunits. Most diagnosed APDS2 patients carry mutations affecting either the splice donor or splice acceptor sites of exon 11 of the PIK3R1 gene respons...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Pediatrics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2021.688022/full |
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| author | Nidia Moreno-Corona Nidia Moreno-Corona Loïc Chentout Loïc Chentout Lucie Poggi Lucie Poggi Romane Thouenon Romane Thouenon Cecile Masson Melanie Parisot Lou Le Mouel Capucine Picard Capucine Picard Capucine Picard Isabelle André Isabelle André Marina Cavazzana Marina Cavazzana Laurence Perrin Anne Durandy Anne Durandy Saba Azarnoush Sven Kracker Sven Kracker |
| author_facet | Nidia Moreno-Corona Nidia Moreno-Corona Loïc Chentout Loïc Chentout Lucie Poggi Lucie Poggi Romane Thouenon Romane Thouenon Cecile Masson Melanie Parisot Lou Le Mouel Capucine Picard Capucine Picard Capucine Picard Isabelle André Isabelle André Marina Cavazzana Marina Cavazzana Laurence Perrin Anne Durandy Anne Durandy Saba Azarnoush Sven Kracker Sven Kracker |
| author_sort | Nidia Moreno-Corona |
| collection | DOAJ |
| description | Activated PI3-kinase-δ syndrome 2 (APDS2) is caused by autosomal dominant mutations in the PIK3R1 gene encoding the p85α, p55α, and p50α regulatory subunits. Most diagnosed APDS2 patients carry mutations affecting either the splice donor or splice acceptor sites of exon 11 of the PIK3R1 gene responsible for an alternative splice product and a shortened protein. The clinical presentation of APDS2 patients is highly variable, ranging from mild to profound combined immunodeficiency features as massive lymphoproliferation, increased susceptibility to bacterial and viral infections, bronchiectasis, autoimmune manifestations, and occurrence of cancer. Non-immunological features such as growth retardation and neurodevelopmental delay have been reported for APDS2 patients. Here, we describe a patient suffering from an APDS2 associated with a Smith–Magenis syndrome (SMS), a complex genetic disorder affecting, among others, neurological manifestations and review the literature describing neurodevelopmental impacts in APDS2 and other PIDs/monogenetic disorders associated with dysregulated PI3K signaling. |
| first_indexed | 2024-12-19T18:32:06Z |
| format | Article |
| id | doaj.art-7550814d44e942aba4bf0bf01ddc33f7 |
| institution | Directory Open Access Journal |
| issn | 2296-2360 |
| language | English |
| last_indexed | 2024-12-19T18:32:06Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pediatrics |
| spelling | doaj.art-7550814d44e942aba4bf0bf01ddc33f72022-12-21T20:10:41ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602021-06-01910.3389/fped.2021.688022688022Two Monogenetic Disorders, Activated PI3-Kinase-δ Syndrome 2 and Smith–Magenis Syndrome, in One Patient: Case Report and a Literature Review of Neurodevelopmental Impact in Primary Immunodeficiencies Associated With Disturbed PI3K SignalingNidia Moreno-Corona0Nidia Moreno-Corona1Loïc Chentout2Loïc Chentout3Lucie Poggi4Lucie Poggi5Romane Thouenon6Romane Thouenon7Cecile Masson8Melanie Parisot9Lou Le Mouel10Capucine Picard11Capucine Picard12Capucine Picard13Isabelle André14Isabelle André15Marina Cavazzana16Marina Cavazzana17Laurence Perrin18Anne Durandy19Anne Durandy20Saba Azarnoush21Sven Kracker22Sven Kracker23Université de Paris, Imagine Institute, Paris, FranceLaboratory of Human Lymphohematopoiesis, INSERM UMR 1163, Paris, FranceUniversité de Paris, Imagine Institute, Paris, FranceLaboratory of Human Lymphohematopoiesis, INSERM UMR 1163, Paris, FranceUniversité de Paris, Imagine Institute, Paris, FranceLaboratory of Human Lymphohematopoiesis, INSERM UMR 1163, Paris, FranceUniversité de Paris, Imagine Institute, Paris, FranceLaboratory of Human Lymphohematopoiesis, INSERM UMR 1163, Paris, FranceParis-Descartes Bioinformatics Platform, Imagine Institute, Paris, FranceGenomics Core Facility, Institut Imagine-Structure Fédérative de Recherche Necker, INSERM U1163 et INSERM US24/CNRS UMS3633, Université de Paris, Paris, FranceHospital Robert Debré, Pediatric Immune-Hematology Service, Paris, FranceUniversité de Paris, Imagine Institute, Paris, FranceNecker Hospital, Pediatric Hematology-Immunology and Rheumatology Unit, Assistance publique des hôpitaux de Paris (APHP), Paris, FranceParis Hospital, Study Center for Primary Immunodeficiencies—APHP, Paris, FranceUniversité de Paris, Imagine Institute, Paris, FranceLaboratory of Human Lymphohematopoiesis, INSERM UMR 1163, Paris, FranceUniversité de Paris, Imagine Institute, Paris, FranceNecker Hospital, Biotherapy and Clinical Investigation Centre—APHP, Paris, FranceHospital Robert Debré, Pediatric Immune-Hematology Service, Paris, FranceUniversité de Paris, Imagine Institute, Paris, FranceLaboratory of Human Lymphohematopoiesis, INSERM UMR 1163, Paris, FranceHospital Robert Debré, Pediatric Immune-Hematology Service, Paris, FranceUniversité de Paris, Imagine Institute, Paris, FranceLaboratory of Human Lymphohematopoiesis, INSERM UMR 1163, Paris, FranceActivated PI3-kinase-δ syndrome 2 (APDS2) is caused by autosomal dominant mutations in the PIK3R1 gene encoding the p85α, p55α, and p50α regulatory subunits. Most diagnosed APDS2 patients carry mutations affecting either the splice donor or splice acceptor sites of exon 11 of the PIK3R1 gene responsible for an alternative splice product and a shortened protein. The clinical presentation of APDS2 patients is highly variable, ranging from mild to profound combined immunodeficiency features as massive lymphoproliferation, increased susceptibility to bacterial and viral infections, bronchiectasis, autoimmune manifestations, and occurrence of cancer. Non-immunological features such as growth retardation and neurodevelopmental delay have been reported for APDS2 patients. Here, we describe a patient suffering from an APDS2 associated with a Smith–Magenis syndrome (SMS), a complex genetic disorder affecting, among others, neurological manifestations and review the literature describing neurodevelopmental impacts in APDS2 and other PIDs/monogenetic disorders associated with dysregulated PI3K signaling.https://www.frontiersin.org/articles/10.3389/fped.2021.688022/fullAPDS2PI3K signalingPIK3R1primary immunodeficiencyneurodevelopmental impact |
| spellingShingle | Nidia Moreno-Corona Nidia Moreno-Corona Loïc Chentout Loïc Chentout Lucie Poggi Lucie Poggi Romane Thouenon Romane Thouenon Cecile Masson Melanie Parisot Lou Le Mouel Capucine Picard Capucine Picard Capucine Picard Isabelle André Isabelle André Marina Cavazzana Marina Cavazzana Laurence Perrin Anne Durandy Anne Durandy Saba Azarnoush Sven Kracker Sven Kracker Two Monogenetic Disorders, Activated PI3-Kinase-δ Syndrome 2 and Smith–Magenis Syndrome, in One Patient: Case Report and a Literature Review of Neurodevelopmental Impact in Primary Immunodeficiencies Associated With Disturbed PI3K Signaling Frontiers in Pediatrics APDS2 PI3K signaling PIK3R1 primary immunodeficiency neurodevelopmental impact |
| title | Two Monogenetic Disorders, Activated PI3-Kinase-δ Syndrome 2 and Smith–Magenis Syndrome, in One Patient: Case Report and a Literature Review of Neurodevelopmental Impact in Primary Immunodeficiencies Associated With Disturbed PI3K Signaling |
| title_full | Two Monogenetic Disorders, Activated PI3-Kinase-δ Syndrome 2 and Smith–Magenis Syndrome, in One Patient: Case Report and a Literature Review of Neurodevelopmental Impact in Primary Immunodeficiencies Associated With Disturbed PI3K Signaling |
| title_fullStr | Two Monogenetic Disorders, Activated PI3-Kinase-δ Syndrome 2 and Smith–Magenis Syndrome, in One Patient: Case Report and a Literature Review of Neurodevelopmental Impact in Primary Immunodeficiencies Associated With Disturbed PI3K Signaling |
| title_full_unstemmed | Two Monogenetic Disorders, Activated PI3-Kinase-δ Syndrome 2 and Smith–Magenis Syndrome, in One Patient: Case Report and a Literature Review of Neurodevelopmental Impact in Primary Immunodeficiencies Associated With Disturbed PI3K Signaling |
| title_short | Two Monogenetic Disorders, Activated PI3-Kinase-δ Syndrome 2 and Smith–Magenis Syndrome, in One Patient: Case Report and a Literature Review of Neurodevelopmental Impact in Primary Immunodeficiencies Associated With Disturbed PI3K Signaling |
| title_sort | two monogenetic disorders activated pi3 kinase δ syndrome 2 and smith magenis syndrome in one patient case report and a literature review of neurodevelopmental impact in primary immunodeficiencies associated with disturbed pi3k signaling |
| topic | APDS2 PI3K signaling PIK3R1 primary immunodeficiency neurodevelopmental impact |
| url | https://www.frontiersin.org/articles/10.3389/fped.2021.688022/full |
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