Changes in nuclear morphology are common in malignant tumors, but the underlying molecular mechanisms remain poorly understood. Lamins is involved in supporting nuclear structure, and the expression of Lamins is the molecular basis for nuclear morphological changes during tumor progression. In recent years, the research on the relationship between Lamins and malignant tumors has made great progress. Lamins is of great value in the diagnosis, treatment, and prognosis of various malignant tumors.
Cell Nucleus ; Humans ; Lamins/genetics* ; Neoplasms/genetics* ; Prognosis

Dilated cardiomyopathy (DCM) is characterized by cardiac dilation and systolic dysfunction. So far sixteen genes have been shown to cause autosomal dominant familial dilated cardiomyopathy (FDC). We identified a large Korean family from the Jeju island showing a clear Mendelian inheritance of FDC. A genomewide linkage scan at 9 cM marker density identified a peak multipoint LOD score of 2.82 at D1S195. Haplotyping of the region with 15 additional markers defined a candidate interval that included a known candidate gene encoding the lamin A/C (LMNA). Sequencing of the LMNA exons revealed one missense mutation at C568T (Arg190Trp) in the alpha-helical rod domain of the LMNA gene cosegregating with FDC with conduction-system disease. The same mutation was found in patients of another Korean family with FDC without conduction-system disease. Upon screening 14 sporadic DCM cases, we found three LMNA mutations including a case having a previously described (Glu161Lys) mutation and two having novel mutations (Glu53Val and Glu186Lys). Our results suggest that variable genotypes of laminopathy are implicated in not only familial but also considerable proportion of sporadic DCM.
Pedigree ; Mutation/genetics ; Molecular Sequence Data ; Male ; Lamins/classification/*genetics ; Korea ; Humans ; Genetic Predisposition to Disease ; Female ; Cardiomyopathy, Dilated/*genetics/*pathology ; Base Sequence ; Amino Acid Sequence ; Adult

<b>OBJECTIVEb>To clone human gastric cancer related gene and to analyze its expression profile in gastric mucosal tissues.

<b>METHODSb>Paired tumor, paratumor and non-tumor specimens from 7 gastric adenocarcinoma patients (male 4, female 3, with average age 51 +/- 18 years) were studied by means of fluorescent differential display reverse transcription polymerase chain reaction (DDRT-PCR). The differentially expressed cDNA bands of interest were cloned and analyzed by Northern blot and in situ hybridization. Thirty cases (male 23 female 7 with average age 59 +/- 8 years) of paired paraffin-embedded gastric tumor and non-tumor tissues were used in in situ hybridization analysis.

<b>RESULTSb>A gene expressed much lower in 6 out of 7 tested tumor samples than in their normal and paratumor counterparts was identified. It was named GCRG123. Northern blot analysis confirmed the differential expression. Human multiple tissue Northern blot analysis showed that GCRG123 expressed in various adult human tissues including thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocyte. Sequence analysis revealed that GCRG123 (GenBank accession number AF454554) was a lamin like protein gene. It had one open reading frame which consisted of 49 amino acids (GenBank accession number AAL61668.1). In situ hybridization analysis showed a high GCRG123 expression level in normal gastric epithelium and pylori glands, but low expression level in tumor as well as dysplasia and most intestinal metaplasia at the paratumor regions.

<b>CONCLUSIONb>A lamin-like protein gene was identified in human gastric mucosa, it is down-regulated in gastric cancer and its precancerous leisions.

Adult ; Aged ; Blotting, Northern ; Cloning, Molecular ; DNA, Neoplasm ; chemistry ; genetics ; Down-Regulation ; genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization ; Lamins ; genetics ; Male ; Middle Aged ; Molecular Sequence Data ; RNA, Messenger ; genetics ; metabolism ; Sequence Analysis, DNA ; Stomach Neoplasms ; genetics

The eukaryotic genome is folded into higher-order conformation accompanied with constrained dynamics for coordinated genome functions. However, the molecular machinery underlying these hierarchically organized three-dimensional (3D) chromatin architecture and dynamics remains poorly understood. Here by combining imaging and sequencing, we studied the role of lamin B1 in chromatin architecture and dynamics. We found that lamin B1 depletion leads to detachment of lamina-associated domains (LADs) from the nuclear periphery accompanied with global chromatin redistribution and decompaction. Consequently, the inter-chromosomal as well as inter-compartment interactions are increased, but the structure of topologically associating domains (TADs) is not affected. Using live-cell genomic loci tracking, we further proved that depletion of lamin B1 leads to increased chromatin dynamics, owing to chromatin decompaction and redistribution toward nucleoplasm. Taken together, our data suggest that lamin B1 and chromatin interactions at the nuclear periphery promote LAD maintenance, chromatin compaction, genomic compartmentalization into chromosome territories and A/B compartments and confine chromatin dynamics, supporting their crucial roles in chromatin higher-order structure and chromatin dynamics.
Chromatin ; Chromosomes ; Genome ; Humans ; Lamin Type B/genetics*

Lamin B1 is one of the essential members of the nuclear lamina protein family. Its main function is to maintain the integrity of nuclear skeleton, as well as to participate in the cell proliferation and aging by affecting the chromosome distribution. gene expression, and DNA damage repair. The abnormal expression of lamin B1 is related to certain diseases, including neurological diseases [e.g. neural tube defects (NDTs), adult-onset autosomal dominant leukodystrophy (ADLD)] and tumors (e.g. pancreatic cancer). It is also a potential tumor marker as well as drug target. Further research on lamin B1 will help people understand the molecular mechanism of the emergence and development of neural system diseases and tumors, and define a new future in drug target.
Cell Nucleus ; Gene Expression ; Humans ; Lamin Type B ; physiology ; Neoplasms ; Nervous System Diseases

No abstract available.
Cardiomyopathy, Dilated* ; Humans ; Lamin Type A ; Twins, Monozygotic*

Cardiomyopathy, Dilated ; genetics ; Lamin Type A ; genetics

Humans ; Cardiomyopathies/genetics* ; Laminopathies ; Lamin Type A/genetics* ; Mutation

Hutchinson-Gilford progeria syndrome (HGPS) is a rare condition originally described by Hutchinson in 1886. Death result from cardiac complications in the majority of cases and usually occurs at average age of thirteen years. A 4-yr old boy had typical clinical findings such as short stature, craniofacial disproportion, alopecia, prominent scalp veins and sclerodermatous skin. This abnormal appearance began at age of 1 yr. On serological and hormonal evaluation, all values are within normal range. He was neurologically intact with motor and mental development. An echocardiogram showed calcification of aortic and mitral valves. Hypertrophy of internal layer at internal carotid artery suggesting atherosclerosis was found by carotid doppler sonography. He is on low dose aspirin to prevent thromboembolic episodes and on regular follow up. Gene study showed typical G608G (GGC- > GGT) point mutation at exon 11 in LMNA gene. This is a rare case of Hutchinson-Gilford progeria syndrome confirmed by genetic analysis in Korea.
Child, Preschool ; Humans ; Lamin Type A/*genetics ; Male ; Point Mutation ; Progeria/diagnosis/*genetics ; Prognosis ; Republic of Korea

<b>BACKGROUNDb>Mutations of the LMNA gene encoding lamin A and C are associated with dilated cardiomyopathy (DCM), conduction system defects and skeletal muscle dystrophy. Here we report a family with a mutation of the LMNA gene to identify the relationship between genotype and phenotype.

<b>METHODSb>All 30 members of the family underwent clinical and genetic evaluation. A mutation analysis of the LMNA gene was performed. All of the 12 exons of LMNA gene were extended with polymerase chain reaction (PCR) and the PCR products were screened for gene mutation by direct sequencing.

<b>RESULTSb>Ten members of the family had limb-girdle muscular dystrophy (LGMD) and 6 are still alive. Two patients suffered from DCM. Cardiac arrhythmias included atrioventricular block and atrial fibrillation; sudden death occurred in 2 patients. The pattern of inheritance was autosomal dominant. Mutation c.73C > G (R25G) in exon 1 encoding the globular domains was confirmed in all of the affected members, resulting in the conversion of arginine (Arg) to glycine (Gly).

<b>CONCLUSIONSb>The mutation R25G in exon 1 of LMNA gene we reported here in a Chinese family had a phenotype of malignant arrhythmia and mild LGMD, suggesting that patients with familial DCM, conduction system defects and skeletal muscle dystrophy should be screened by genetic testing for the LMNA gene.

Adult ; Cardiomyopathy, Dilated ; genetics ; Exons ; Humans ; Lamin Type A ; genetics ; Muscular Dystrophies, Limb-Girdle ; genetics ; Mutation