Abstract:
:Germline mutations in LKB1 have been reported to underlie familial Peutz-Jeghers syndrome (PJS) with intestinal hamartomatous polyps and an elevated risk of various neoplasms. To investigate the prevalence of LKB1 germline mutations in PJS more generally, we studied samples from 33 unrelated PJS patients including eight non-familial sporadic patients, 20 familial patients and five patients with unknown family history. Nineteen germline mutations were identified, 12 (60%) in familial and four (50%) in sporadic cases. LKB1 mutations were not detected in 14 (42%) patients, indicating that the existence of additional minor PJS loci cannot be excluded. LKB1 is predicted to encode a serine/threonine kinase. To demonstrate the putative Lkb1 kinase function and to study the consequences of LKB1 mutations in PJS and sporadic tumors, we have analyzed the kinase activity of wild-type and mutant Lkb1 proteins. Interestingly, while most of the small deletions or missense mutations resulted in loss-of-function alleles, one missense mutation (G163D) previously identified in a sporadic testicular tumor demonstrated severely impaired but detectable kinase activity.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Ylikorkala A,Avizienyte E,Tomlinson IP,Tiainen M,Roth S,Loukola A,Hemminki A,Johansson M,Sistonen P,Markie D,Neale K,Phillips R,Zauber P,Twama T,Sampson J,Järvinen H,Mäkelä TP,Aaltonen LAdoi
10.1093/hmg/8.1.45subject
Has Abstractpub_date
1999-01-01 00:00:00pages
45-51issue
1eissn
0964-6906issn
1460-2083pii
ddc007journal_volume
8pub_type
杂志文章abstract::The group of dominant non-dystrophic myotonias, comprising disorders characterized by clinically similar forms of myogenic muscle stiffness, is genetically inhomogeneous. Dominant myotonia congenita (Thomsen's disease) is linked to CLCN1, the gene encoding the major muscle chloride channel, localized on chromosome 7q3...
journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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doi:10.1093/hmg/8.12.2205
更新日期:1999-11-01 00:00:00
abstract::By GenBank database searches and PCR, we have identified a novel human Bcl2-like gene, Bcl2-L-10, which contains conserved BH4, BH1 and BH2 domains but lacks BH3 domain. The Bcl2-L-10 gene has been assigned to chromosome 15q21.2. Transfection experiments demonstrated that Bcl2-L-10 can block apoptosis induced by inter...
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journal_title:Human molecular genetics
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abstract::Parental genetic relatedness may lead to adverse health and fitness outcomes in the offspring. However, the degree to which it affects human delivery timing is unknown. We use genotype data from ≃25 000 parent-offspring trios from the Norwegian Mother, Father and Child Cohort Study to optimize runs of homozygosity (RO...
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
pub_type: 杂志文章,评审
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更新日期:1994-01-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
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journal_title:Human molecular genetics
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1994-11-01 00:00:00
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2019-09-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章,meta分析
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更新日期:2017-05-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章,评审
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更新日期:2008-04-15 00:00:00
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:1999-09-01 00:00:00
abstract::Spinal and bulbar muscular atrophy (SBMA, also known as Kennedy's disease) is one of nine neurodegenerative disorders that are caused by expansion of polyglutamine-encoding CAG repeats. Intracellular accumulation of abnormal proteins in these diseases, a pathological hallmark, is associated with defects in protein hom...
journal_title:Human molecular genetics
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abstract::Hirschsprung disease (HSCR) is a frequent neurocristopathy characterized by the absence of submucosal and myenteric plexuses in a variable length of the gastrointestinal tract. Pedigrees and segregation analyses suggested the involvement of one or several dominant genes with low penetrance in HSCR. Considering that RE...
journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:1998-09-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2008-11-01 00:00:00
abstract::Mutations in Fused in sarcoma (FUS) gene cause a subset of familial amyotrophic lateral sclerosis (ALS), a fatal motor neuron degenerative disease. Wild-type FUS is largely localized in the nucleus, but mutant FUS accumulates in the cytoplasm and forms inclusions. It is unclear whether FUS depletion from the nucleus o...
journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2015-09-15 00:00:00
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journal_title:Human molecular genetics
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更新日期:2007-06-01 00:00:00
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journal_title:Human molecular genetics
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更新日期:2013-12-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2014-01-01 00:00:00