Mutations in the Human Laminin β2 (LAMB2) Gene and the Associated Phenotypic Spectrum

Autor: Mikhail Kagan, Verena Matejas, Laurie L. Seaver, Steffen Uebe, Ana Medeira, Ariana Kariminejad, Květa Bláhová, Friedhelm Hildebrandt, Priya Gajjar, Anand A. Saggar, Jörg Dötsch, Elke Wühl, Michel M. Pierson, Detlef Bockenhauer, Pierre Cochat, Faisal F. Alkandari, Markus J. Kemper, Mehmet Baha Aytac, Jutta Muscheites, Alexey A. Tsygin, Hae Il H.I. Cheong, Iwona Maruniak-Chudek, Corinne Antignac, Jillene J. Kogan, Margaret Barrow, Martin Zenker, Hester Y. Kroes, Eberhard Kuwertz-Bröking, Mohnish Suri, Bernward B. Hinkes, Amy Feldman Lewanda, Ellen E. Annexstad, Raoul C.M. Hennekam, Aleksandra Zurowska, Françoise Janssen, Jens Koenig, Lihadh Al-Gazali, Patrick Niaudet
Přispěvatelé: Institute of Human Genetics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Pediatric Nephrology, University Children's Hospital, Howard Hughes Medical Institute and Departments of Pediatrics and Human Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Pediatric Department, Mubarak Alkabeer Hospital, Department of Pediatrics, Faculty of Medicine and Health Sciences, UAE University, Oslo University Hospital [Oslo], Department of Pediatric Nephrology, Istanbul University, Cerrahpaþa Medical Faculty, Leicester Royal Infirmary, University Hospitals Leicester, University Hospital Motol, 2nd Faculty of Medicine, Charles University Prague, Great Ormond Street Hospital for Children [London] (GOSH), Dept. of Pediatrics, Seoul National University Children's Hospital, Department of Neonatal Intensive Care, Medical University of Silesia, Katowice, Département de Pédiatrie, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Paediatric Nephrology, Dept. of Paediatric Medicine, University of Cape Town, Dept. of Clinical Genetics, Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), Department of Gastroenterology and Nephrology, Orenburg Regional Children's Hospital, Kariminejad-Najmabadi Pathology& Genetics Center, Kariminejad-Najmabadi Pathology & Genetics Center, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University Children's Hospital, Munster, Department of Human Genetics, Cincinnati Children's Hospital Medical Center, Inova Fairfax Hospital for Children, Hospital Santa Maria, University Children's Hospital, University of Rostock, Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University Children's Hospital Nancy, St. George's University of London, Kapiolani Medical Specialists and Department of Pediatricslaurie.seaver@kapiolani.org, John A. Burns School of Medicine, University of Hawaii-University of Hawaii, Clinical Genetics Service, Nottingham University Hospitals NHS Trust, Nephrology, The Scientific Center of Children's Health, Center for Pediatric and Adolescent Medicine, University of Heidelberg, Department Pediatric & Adolescent Nephrology & Hypertension, Medical University Gdansk, Pediatrics, CHU Necker - Enfants Malades [AP-HP], Institute of Human Genetics, University Hospital Magdeburg, University Hospital Erlangen, Oslo University Hospital, Great Ormond Street Hospital for Children [London] ( GOSH ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Hôpital Universitaire des Enfants - Reine Fabiola, Université Libre de Bruxelles, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] ( UKE ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Medical University of Silesia (SUM), ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, Paediatrics
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: Human Mutation
Human Mutation, Wiley, 2010, 31 (9), pp.992. ⟨10.1002/humu.21304⟩
Human Mutation, Wiley, 2010, 31 (9), pp.992. 〈10.1002/humu.21304〉
Human mutation, 31(9), 992-1002. Wiley-Liss Inc.
ISSN: 1059-7794
1098-1004
Popis: International audience; Mutations of LAMB2 typically cause autosomal recessive Pierson syndrome, a disorder characterized by congenital nephrotic syndrome, ocular and neurologic abnormalities, but may occasionally be associated with milder or oligosymptomatic disease variants. LAMB2 encodes the basement membrane protein laminin β2 which is incorporated in specific heterotrimeric laminin isoforms and has an expression pattern corresponding to the pattern of organ manifestations in Pierson syndrome. Herein we review all previously reported and several novel LAMB2 mutations in relation to the associated phenotype in patients from 39 unrelated families. The majority of disease-causing LAMB2 mutations are truncating, consistent with the hypothesis that loss of laminin β2 function is the molecular basis of Pierson syndrome. While truncating mutations are distributed across the entire gene, missense mutations are clearly clustered in the N-terminal LN domain, which is important for intermolecular interactions. There is an association of missense mutations and small in frame deletions with a higher mean age at onset of renal disease and with absence of neurologic abnormalities, thus suggesting that at least some of these may represent hypomorphic alleles. Nevertheless, genotype alone does not appear to explain the full range of clinical variability, and therefore hitherto unidentified modifiers are likely to exist.
Databáze: OpenAIRE
Externí odkaz: