Nuclear Lamins: Laminopathies and Their Role in Premature Ageing

Broers, Jos L. V.; Ramaekers, Frans C. S.; Bonne, Gisèle; Yaou, Rabah Ben; Hutchison, Christopher J.

doi:10.1152/physrev.00047.2005

Cited by 508 publications

(545 citation statements)

References 404 publications

(510 reference statements)

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“…In the nuclear envelope, MLIP (also known as CIP) directly interacts with the N-terminal region of lamin (LMNA) [19]. Dominant mutations in LMNA cause DCM and other hereditary multisystemic diseases and several pathogenic mutations of LMNA are located in its MLIP interacting domain [20]. In mice, Mlip interacts with Isl1, a transcription factor required for cardiomyocyte differentiation, and represses its transcriptional activity [21].…”

Section: Discussionmentioning

confidence: 99%

Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy

Esslinger

Garnier

Korniat

et al. 2018

Archives of Cardiovascular Diseases Supplements

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AimsDilated cardiomyopathy (DCM) is an important cause of heart failure with a strong familial component. We performed an exome-wide array-based association study (EWAS) to assess the contribution of missense variants to sporadic DCM. Data Availability Statement: Genotyping data and phenotypes of the patients and controls are not available due to signed consent and ethical limitations. These data will not be available upon request. However, the summary statistics for association of all SNPs are included as supplementary files S5 and S6 Tables. Funding:The study was supported by the Leducq Transatlantic Network: "Genomic, epigenomic and systems dissection of mechanisms underlying Methods and results116,855 single nucleotide variants (SNVs) were analyzed in 2796 DCM patients and 6877 control subjects from 6 populations of European ancestry. We confirmed two previously identified associations with SNVs in BAG3 and ZBTB17 and discovered six novel DCMassociated loci (Q-value<0.01). The lead-SNVs at novel loci are common and located in TTN, SLC39A8, MLIP, FLNC, ALPK3 and FHOD3. In silico fine mapping identified HSPB7 as the most likely candidate at the ZBTB17 locus. Rare variant analysis (MAF<0.01) demonstrated significant association for TTN variants only (P = 0.0085). All candidate genes but one (SLC39A8) exhibit preferential expression in striated muscle tissues and mutations in TTN, BAG3, FLNC and FHOD3 are known to cause familial cardiomyopathy. We also investigated a panel of 48 known cardiomyopathy genes. Collectively, rare (n = 228, P = 0.0033) or common (n = 36, P = 0.019) variants with elevated in silico severity scores were associated with DCM, indicating that the spectrum of genes contributing to sporadic DCM extends beyond those identified here. ConclusionWe identified eight loci independently associated with sporadic DCM. The functions of the best candidate genes at these loci suggest that proteostasis regulation might play a role in DCM pathophysiology.

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Section: Discussionmentioning

confidence: 99%

Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy

Esslinger

Garnier

Korniat

et al. 2018

Archives of Cardiovascular Diseases Supplements

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“…described to cause Dunnigan-type lipodystrophy [Broers et al, 2006;Burke and Stewart, 2006;Cao and Hegele, 2000;Capell and Collins, 2006;Rogers et al, 2005;Shackleton et al, 2000;Speckman et al, 2000;Vigouroux et al, 2000]. Arginine mutation clusters are very common in GFAP: 31 of them are in the 1A domain at codons R79 (equivalent position to K14:R125) and R88 (corresponding to K14:R134), and 30 are in the 2A domain at residue R239 (corresponding to K14:R288).…”

Section: Analysis Of Datasetsmentioning

confidence: 99%

The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases

et al. 2008

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Communicated by A. Jamie CuticchiaWe describe a revised and expanded database on human intermediate filament proteins, a major component of the eukaryotic cytoskeleton. The family of 70 intermediate filament genes (including those encoding keratins, desmins, and lamins) is now known to be associated with a wide range of diverse diseases, at least 72 distinct human pathologies, including skin blistering, muscular dystrophy, cardiomyopathy, premature aging syndromes, neurodegenerative disorders, and cataract. To date, the database catalogs 1,274 manually-curated pathogenic sequence variants and 170 allelic variants in intermediate filament genes from over 459 peer-reviewed research articles. Unrelated cases were collected from all of the six sequence homology groups and the sequence variations were described at cDNA and protein levels with links to the related diseases and reference articles. The mutations and polymorphisms are presented in parallel with data on protein structure, gene, and chromosomal location and basic information on associated diseases. Detailed statistics relating to the variants records in the database are displayed by homology group, mutation type, affected domain, associated diseases, and nucleic and amino acid substitutions. Multiple sequence alignment algorithms can be run from queries to determine DNA or protein sequence conservation. Literature sources can be interrogated within the database and external links are provided to public databases. The database is freely and publicly accessible online at www.interfil.org (last accessed 13 September 2007). Users can query the database by various keywords and the search results can be downloaded. It is anticipated that the Human Intermediate Filament Database (HIFD) will provide a useful resource to study human genome variations for basic scientists, clinicians, and students alike. Hum Mutat 29(3), [351][352][353][354][355][356][357][358][359][360] 2008.

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“…4,5 Lamins are major components of the nuclear lamina, a filamentous meshwork underlying the inner nuclear membrane involved in nuclear shape, nuclear pore complex spacing and resistance to mechanical stress. Moreover, by their numerous interactions and nucleoplasmic localization in the nuclear matrix, lamins have been involved in many other major nuclear functions, including regulation of gene expression, chromatin organization and DNA replication and repair (for review, see Broers et al 6 and Prokocimer et al 7 ).…”

Section: Introductionmentioning

confidence: 99%

New ZMPSTE24 (FACE1) mutations in patients affected with restrictive dermopathy or related progeroid syndromes and mutation update

et al. 2013

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Restrictive dermopathy (RD) is a rare and extremely severe congenital genodermatosis, characterized by a tight rigid skin with erosions at flexure sites, multiple joint contractures, low bone density and pulmonary insufficiency generally leading to death in the perinatal period. RD is caused in most patients by compound heterozygous or homozygous ZMPSTE24 null mutations. This gene encodes a metalloprotease specifically involved in lamin A post-translational processing. Here, we report a total of 16 families for whom diagnosis and molecular defects were clearly established. Among them, we report seven new ZMPSTE24 mutations, identified in classical RD or Mandibulo-acral dysplasia (MAD) affected patients. We also report nine families with one or two affected children carrying the common, homozygous thymine insertion in exon 9 and demonstrate the lack of a founder effect. In addition, we describe several new ZMPSTE24 variants identified in unaffected controls or in patients affected with non-classical progeroid syndromes. In addition, this mutation update includes a comprehensive search of the literature on previously described ZMPSTE24 mutations and associated phenotypes. Our comprehensive analysis of the molecular pathology supported the general rule: complete loss-of-function of ZMPSTE24 leads to RD, whereas other less severe phenotypes are associated with at least one haploinsufficient allele.

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Nuclear Lamins: Laminopathies and Their Role in Premature Ageing

Cited by 508 publications

References 404 publications

Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy

Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy

The Human Intermediate Filament Database: comprehensive information on a gene family involved in many human diseases

New ZMPSTE24 (FACE1) mutations in patients affected with restrictive dermopathy or related progeroid syndromes and mutation update

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