Human KVLQT1 gene shows tissue-specific imprinting and encompasses Beckwith-Wiedemann syndrome chromosomal rearrangements

Nat Genet. 1997 Feb;15(2):181-5. doi: 10.1038/ng0297-181.


Genomic imprinting is an epigenetic chromosomal modification in the gamete or zygote causing preferential expression of a specific parental allele in somatic cells of the offspring. We and others have identified three imprinted human genes on 11p15.5, IGF2, H19, and p57KIP2, although the latter gene is separated by 700 kb from the other two, and it is unclear whether there are other imprinted genes within this large interval. We previously mapped an embryonal tumour suppressor gene to this region, as well as five balanced germline chromosomal rearrangement breakpoints from patients with Beckwith-Wiedemann syndrome (BWS), a condition characterized by prenatal overgrowth and cancer. We isolated the upstream exons of the previously identified gene KVLQT1, which causes the familial cardiac defect long-QT (LQT) syndrome. We found that KVLQT1 spans much of the interval between p57KIP2 and IGF2, and that it is also imprinted. We demonstrated that the gene is disrupted by chromosomal rearrangements in BWS patients, as well as by a balanced chromosomal translocation in an embryonal rhabdoid tumour. Furthermore, the lack of parent-of-origin effect in LQT syndrome appears to be due to relative lack of imprinting in the affected tissue, cardiac muscle, representing a novel mechanism for variable penetrance of a human disease gene.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Beckwith-Wiedemann Syndrome / genetics*
  • Chromosome Aberrations*
  • Chromosomes, Human, Pair 11 / genetics*
  • Chromosomes, Human, Pair 11 / ultrastructure
  • Epistasis, Genetic
  • Female
  • Fetal Proteins / biosynthesis
  • Fetal Proteins / genetics
  • Gene Deletion*
  • Gene Expression Regulation, Developmental
  • Genes
  • Genomic Imprinting*
  • Humans
  • KCNQ Potassium Channels
  • KCNQ1 Potassium Channel
  • Kidney Neoplasms / genetics
  • Male
  • Molecular Sequence Data
  • Neoplastic Syndromes, Hereditary / genetics
  • Organ Specificity
  • Polymorphism, Genetic
  • Polymorphism, Single-Stranded Conformational
  • Potassium Channels / biosynthesis
  • Potassium Channels / genetics*
  • Potassium Channels, Voltage-Gated*
  • Translocation, Genetic / genetics
  • Wilms Tumor / genetics


  • Fetal Proteins
  • KCNQ Potassium Channels
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Potassium Channels
  • Potassium Channels, Voltage-Gated