Microdeletion of LIT1 in Familial Beckwith-Wiedemann Syndrome
The American Journal of Human GeneticsPublished 4 October 2004Open access
Emily Niemitz, Michael R. DeBaun, Jonathan Fallon, Kazuhiro Murakami, Hiroyuki Kugoh, Mitsuo Oshimura
Citations132
SJR quartileQ1
SJR score4.53
SNIP2.47
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
A microdeletion including the entire LIT1 gene is reported, providing genetic confirmation of the importance of this gene region in BWS and indicating deletion of an element important for the regulation of p57(KIP2) expression.
Abstract
Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth, midline abdominal wall defects, macroglossia, and embryonal tumors, is a model for understanding the relationship between genomic imprinting, human development, and cancer. The causes are heterogeneous, involving multiple genes on 11p15 and including infrequent mutation of p57(KIP2) or loss of imprinting of either of two imprinted gene domains on 11p15: LIT1, which is near p57(KIP2), or H19/IGF2. Unlike Prader-Willi and Angelman syndromes, no chromosomal deletions have yet been identified. Here we report a microdeletion including the entire LIT1 gene, providing genetic confirmation of the importance of this gene region in BWS. When inherited maternally, the deletion causes BWS with silencing of p57(KIP2), indicating deletion of an element important for the regulation of p57(KIP2) expression. When inherited paternally, there is no phenotype, suggesting that the LIT1 RNA itself is not necessary for normal development in humans.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
Nature GeneticsInherited microdeletions in the Angelman and Prader–Willi syndromes define an imprinting centre on human chromosome 15
598 Citations1995Karin Buiting, Shinji Saitoh +5 more
A subset of patients with Angelman and Prader–Willi syndrome have apparently normal chromosomes of biparental origin, but abnormal DMA methylation at several loci within chromosome 15q11–13, and probably have a defect in imprinting.
Nature GeneticsRegional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1
464 Citations2002Galina V. Fitzpatrick, Paul D. Soloway +1 more
It is shown that paternal inheritance of a deletion of KvDMR1 results in the de-repression in cis of six genes, including Cdkn1c, which encodes cyclin-dependent kinase inhibitor 1C, and fetuses and adult mice that inherited the deletion from their fathers were 20–25% smaller than their wildtype littermates.
Nature GeneticsLoss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms' tumour
464 Citations1994Marja Steenman, Shirley Rainier +4 more
The data suggest an epigenetic mechanism for inactivation of H19 as a tumour suppressor gene through imprinting of a large domain of the maternal chromosome, which results in a reversal to a paternal epigenotype.
Nature GeneticsDisruption of insulin–like growth factor 2 imprinting in Beckwith–Wiedemann syndrome
425 Citations1993Rosanna Weksberg, Ding Ren Shen +3 more
The view that IGF2 overexpression plays an important role in somatic overgrowth and the development of embryonal tumours further strengthens the view that the BWS phenotype in some patients involves disruption of IGF2 imprinting.
Proceedings of the National Academy of SciencesA maternally methylated CpG island in <i>KvLQT1</i> is associated with an antisense paternal transcript and loss of imprinting in Beckwith–Wiedemann syndrome
407 Citations1999Nancy J. Smilinich, Colleen D. Day +14 more
It is proposed that KvDMR1 and/or its associated antisense RNA (KvLQT1-AS) represents an additional imprinting control element or center in the human 11p15.5 and mouse distal 7 imprinted domains.
Proceedings of the National Academy of SciencesLoss of imprinting of a paternally expressed transcript, with antisense orientation to K <sub>V</sub> LQT1, occurs frequently in Beckwith–Wiedemann syndrome and is independent of insulin-like growth factor II imprinting
358 Citations1999Maxwell P. Lee, Michael R. DeBaun +5 more
It is proposed that 11p15 harbors two imprinted gene domains-a more centromeric domain including KVLQT1 and p57(KIP2), alterations in which are more common in BWS, and a more telomeric domain including IGF2, alterations inWhich are moreCommon in cancer.
Proceedings of the National Academy of SciencesImprinting of the gene encoding a human cyclin-dependent kinase inhibitor, p57KIP2, on chromosome 11p15.
301 Citations1996Satomi Matsuoka, Jeffrey S. Thompson +7 more
It is found that the p57KIP2 gene is imprinted, with preferential expression of the maternal allele, and the biochemical function, chromosomal location, and imprinting match the properties predicted for a tumor suppressor gene at 11p15.5.
Nature MedicineLoss of imprinting in normal tissue of colorectal cancer patients with microsatellite instability
284 Citations1998Hengmi Cui, Isabelle L. Horon +3 more
It is suggested that LOI in tumor and normal tissue identifies most colorectal cancer patients with microsatellite instability in their tumors, and thatLOI may identify an important subset of the population with cancer or at risk of developing cancer.
Human Molecular GeneticsTargeted disruption of the human LIT1 locus defines a putative imprinting control element playing an essential role in Beckwith-Wiedemann syndrome
177 Citations2000Shin‐ichi Horike
It is demonstrated that the Lit1 CpG island can act as a negative regulator in cis for coordinate imprinting at the centromeric domain, thereby suggesting a role for the LIT1 locus in a BWS pathway leading to functional inactivation of p57(KIP2).
Journal of Medical GeneticsSilencing of <i>CDKN1C</i> (<i>p57<sup>KIP2</sup> </i>) is associated with hypomethylation at KvDMR1 in Beckwith–Wiedemann syndrome
145 Citations2003Natacha Diaz-Meyer, C D Day +9 more
An epimutation at KvDMR1, the absence of maternal methylation, causes the aberrant silencing of CDKN1C, some 180 kb away on the maternal chromosome, which may give rise to Beckwith–Wiedemann syndrome.
The American Journal of Human GeneticsLow Frequency of p57KIP2 Mutation in Beckwith-Wiedemann Syndrome
136 Citations1997Maxwell P. Lee, Michael R. DeBaun +4 more
The low frequency of p57KIP2 mutations, as well as the recent discovery of disruption of the K(v)LQT1 gene in patients with chromosomal rearrangements, suggest that BWS can involve disruption of multiple independent 11p15.5 genes.
The American Journal of Human GeneticsCoding Mutations in p57 Are Present in Some Cases of Beckwith-Wiedemann Syndrome but Are Rare or Absent in Wilms Tumors
134 Citations1997Denise O’Keefe, Diem Dao +6 more
Human MutationDiagnosis of haploidy and triploidy based on measurement of gene copy number by real-time PCR
73 Citations2000Klaus Wilke, B�lent Duman +1 more
The development of a method for diagnosis of heterozygous deletions or duplications based on measurement of gene copy number and the presence or absence of the genomic deletion or duplication was unambiguously diagnosed in all individuals.
Nature GeneticsDisruption of an imprinted gene cluster by a targeted chromosomal translocation in mice
50 Citations2001Michele A. Cleary, Catherine D. Van Raamsdonk +4 more
The proposal that chromosomal abnormalities within KCNQ1 that are associated with the human disease Beckwith-Wiedemann syndrome (BWS) may disrupt CDKN1C expression is supported, and the importance of gene clustering for the proper regulation of imprinted genes is underscore.