دورية أكاديمية
أعرض في EDS

The phenotypic and genetic spectrum of patients with heterozygous mutations in cyclin M2 (CNNM2).

التفاصيل البيبلوغرافية
العنوان: The phenotypic and genetic spectrum of patients with heterozygous mutations in cyclin M2 (CNNM2).
المؤلفون: Franken GAC; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Müller D; Department of Pediatric Gastroenterology, Nephrology and Metabolism, Charité Universitäts Medizin, Berlin, Germany., Mignot C; Département de Genetique, Centre de Référence Déficiences Intellectuelles de Causes Rares, Assistance Publique Hôpitaux de Paris, Paris, France., Keren B; Département de Génétique, Groupe Hospitalier, Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, Paris, France., Lévy J; Genetics Department, AP-HP, Robert-Debré University Hospital, Paris, France., Tabet AC; Genetics Department, AP-HP, Robert-Debré University Hospital, Paris, France., Germanaud D; Pediatric Neurology Department, Centre de Référence Déficiences Intellectuelles de Causes Rares, Service de Neurologie Pédiatrique, Hôpital Robert-Debré, Assistance Publique-Hôpitaux de Paris, Paris, France., Tejada MI; Osakidetza Basque Health Service, Cruces University Hospital, Genetics Service and Biocruces Bizkaia Health Research Institute, Barakaldo, Spain.; Spanish Consortium for Research on Rare Diseases (CIBERER), Valencia, Spain., Kroes HY; Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands., Nievelstein RAJ; Department of Pediatric Radiology, University Medical Center Utrecht, Utrecht, The Netherlands., Brimble E; Department of Neurology and Neurological Sciences, Stanford Medicine, Stanford, California, USA., Ruzhnikov M; Department of Neurology and Neurological Sciences, Stanford Medicine, Stanford, California, USA., Claverie-Martin F; Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain., Szczepańska M; Department of Pediatrics, Medical University of Silesia, Katowice, Poland., Ćuk M; Department of Pediatrics, Children's Hospital Zagreb, Zagreb, Croatia., Latta F; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Konrad M; Department of General Pediatrics, University Children's Hospital, Münster, Germany., Martínez-Cruz LA; Structural Biology Unit, Center for Cooperative Research in Biosciences (CIC bioGUNE), Technology Park of Bizkaia, Derio, Spain., Bindels RJM; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Hoenderop JGJ; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Schlingmann KP; Department of General Pediatrics, University Children's Hospital, Münster, Germany., de Baaij JHF; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
المصدر: Human mutation [Hum Mutat] 2021 Apr; Vol. 42 (4), pp. 473-486. Date of Electronic Publication: 2021 Mar 01.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 9215429 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-1004 (Electronic) Linking ISSN: 10597794 NLM ISO Abbreviation: Hum Mutat Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York : Wiley-Liss, c1992-
مواضيع طبية MeSH: Cation Transport Proteins*/genetics , Intellectual Disability*/diagnosis , Intellectual Disability*/genetics, Cyclins/genetics ; Heterozygote ; Humans ; Mutation ; Phenotype
مستخلص: Hypomagnesemia, seizures, and intellectual disability (HSMR) syndrome is a rare disorder caused by mutations in the cyclin M2 (CNNM2) gene. Due to the limited number of cases, extensive phenotype analyses of these patients have not been performed, hindering early recognition of patients. In this study, we established the largest cohort of HSMR to date, aiming to improve recognition and diagnosis of this complex disorder. Eleven novel variants in CNNM2 were identified in nine single sporadic cases and in two families with suspected HSMR syndrome. 25 Mg 2+ uptake assays demonstrated loss-of-function in seven out of nine variants in CNNM2. Interestingly, the pathogenic mutations resulted in decreased plasma membrane expression. The phenotype of those affected by pathogenic CNNM2 mutations was compared with five previously reported cases of HSMR. All patients suffered from hypomagnesemia (0.44-0.72 mmol/L), which could not be fully corrected by Mg 2+ supplementation. The majority of patients (77%) experienced generalized seizures and exhibited mild to moderate intellectual disability and speech delay. Moreover, severe obesity was present in most patients (89%). Our data establish hypomagnesemia, seizures, intellectual disability, and obesity as hallmarks of HSMR syndrome. The assessment of these major features offers a straightforward tool for the clinical diagnosis of HSMR.
(© 2021 The Authors. Human Mutation published by Wiley Periodicals LLC.)
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فهرسة مساهمة: Keywords: CNNM2; HSMR; hypomagnesemia; intellectual disability; obesity
المشرفين على المادة: 0 (CNNM2 protein, human)
0 (Cation Transport Proteins)
0 (Cyclins)
تواريخ الأحداث: Date Created: 20210218 Date Completed: 20220331 Latest Revision: 20220531
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8248058
DOI: 10.1002/humu.24182
PMID: 33600043
قاعدة البيانات: MEDLINE
الوصف
تدمد:1098-1004
DOI:10.1002/humu.24182