Nuclear lamins and laminopathies.
TL;DR: Basic research in cellular and small animal models has produced promising leads for treatments of these rare diseases and the incomplete understanding of pathogenic mechanisms underlying the laminopathies is only starting to be understood.
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Abstract: Nuclear lamins are intermediate filament proteins that polymerize to form the nuclear lamina on the inner aspect of the inner nuclear membrane. Long known to be essential for maintaining nuclear structure and disassembling/reassembling during mitosis in metazoans, research over the past dozen years has shown that mutations in genes encoding nuclear lamins, particularly LMNA encoding the A-type lamins, cause a broad range of diverse diseases, often referred to as laminopathies. Lamins are expressed in all mammalian somatic cells but mutations in their genes lead to relatively tissue-selective disease phenotypes in most cases. While mutations causing laminopathies have been shown to produce abnormalities in nuclear morphology, how these disease-causing mutations or resultant alterations in nuclear structure lead to pathology is only starting to be understood. Despite the incomplete understanding of pathogenic mechanisms underlying the laminopathies, basic research in cellular and small animal models has produced promising leads for treatments of these rare diseases. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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References
Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome
Maria Eriksson,W. Ted Brown,Leslie B. Gordon,Leslie B. Gordon,Michael W. Glynn,Joel Singer,Laura J. Scott,Michael R. Erdos,Christiane M. Robbins,Tracy Moses,Peter Berglund,Amalia Dutra,Evgenia Pak,Sandra G. Durkin,Antonei B. Csoka,Michael Boehnke,Thomas W. Glover,Francis S. Collins +17 more
TL;DR: Evidence of mutations in lamin A (LMNA) as the cause of Hutchinson–Gilford progeria syndrome is presented, and the discovery of the molecular basis of this disease may shed light on the general phenomenon of human ageing.
Lamin a truncation in hutchinson-gilford progeria
Annachiara De Sandre-Giovannoli,Rafaëlle Bernard,Pierre Cau,Claire Navarro,Jeanne Amiel,Irène Boccaccio,Stanislas Lyonnet,Colin L. Stewart,Arnold Munnich,Martine Le Merrer,Nicolas Lévy +10 more
TL;DR: HGPS is an exceedingly rare but typical progeria, clinically characterized by postnatal growth retardation, midface hypoplasia, micrognathia, premature atherosclerosis, absence of subcutaneous fat, and others.
1.4K
Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy
Gisèle Bonne,M R Di Barletta,S. Varnous,H.M. Bécane,EL-Hadi Hammouda,Luciano Merlini,Francesco Muntoni,Cheryl R. Greenberg,Françoise Gary,Jon Andoni Urtizberea,Denis Duboc,Michel Fardeau,Daniela Toniolo,Ketty Schwartz +13 more
TL;DR: This work has mapped the locus for EDMD-AD to an 8-cM interval on chromosome 1q11-q23 in a large French pedigree, and found that the EMD phenotype in four other small families was potentially linked to this locus, and identified four mutations in LMNA that co-segregate with the disease phenotype in the five families.
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Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.
Diane Fatkin,Calum A. MacRae,Takeshi Sasaki,Matthew R. Wolff,Maurizio Porcu,Michael P. Frenneaux,John Atherton,Humberto Vidaillet,Serena Spudich,Umberto De Girolami,Jonathan G. Seidman,Francesco Muntoni,G. W. F. Muehle,Wendy Johnson,Barbara McDonough,Christine E. Seidman +15 more
TL;DR: Missense mutations in the rod domain of the lamin A/C gene provide a genetic cause for dilated cardiomyopathy and indicate that this intermediate filament protein has an important role in cardiac conduction and contractility.
Loss of a-Type Lamin Expression Compromises Nuclear Envelope Integrity Leading to Muscular Dystrophy
Teresa Sullivan,Diana Escalante-Alcalde,Harshida Bhatt,Miriam R. Anver,Narayan K. Bhat,Kunio Nagashima,Colin L. Stewart,Brian Burke +7 more
TL;DR: It is shown that mice lacking A-type lamins develop to term with no overt abnormalities, however, their postnatal growth is severely retarded and is characterized by the appearance of muscular dystrophy.