Paternal uniparental disomy for chromosome 1 revealed by molecular analysis of a patient with pycnodysostosis

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Microsatellite DNA Genotyping and Flow Cytometry Ploidy Analyses of Formalin-fixed Paraffin-embedded Hydatidiform Molar Tissues
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Microsatellite DNA Genotyping and Flow Cytometry Ploidy Analyses of Formalin-fixed Paraffin-embedded Hydatidiform Molar Tissues

Published on: October 20, 2019

B D Gelb1, J P Willner, T M Dunn

  • 1Department of Pediatrics, Mount Sinai School of Medicine, New York, NY, USA. gelb@msvax.mssm.edu

American Journal of Human Genetics
|June 13, 1998
PubMed

Insights

This study identifies a novel mutation causing pycnodysostosis and reveals the first case of paternal uniparental disomy of chromosome 1. This finding confirms that paternal genes on chromosome 1 are not imprinted.

Area of Science:

  • Genetics and Molecular Biology
  • Human Disease and Genetics
  • Epigenetics and Imprinting

Background:

  • Pycnodysostosis is an autosomal recessive skeletal dysplasia caused by cathepsin K deficiency.
  • Uniparental disomy (UPD) occurs when an individual inherits two copies of a chromosome from one parent and none from the other.
  • Genomic imprinting is an epigenetic phenomenon where only one copy of a gene is expressed, depending on its parental origin.

Observation:

  • A patient with pycnodysostosis was found to be homozygous for a novel missense mutation (A277V) in the cathepsin K gene.
  • The mutation was inherited from the father, while the mother had two normal alleles, suggesting paternal UPD.
  • Cytogenetic and polymorphic DNA marker analyses confirmed paternal UPD of chromosome 1 with partial isodisomy, resulting from a meiosis II nondisjunction event.

Findings:

  • The patient exhibited typical pycnodysostosis features but had normal birth measurements and psychomotor development.
  • This case represents the first documented instance of paternal uniparental disomy for chromosome 1.
  • The inheritance pattern provided conclusive evidence against imprinting for paternally derived genes on chromosome 1.

Implications:

  • This study expands the understanding of pycnodysostosis genetics and the mechanisms of uniparental disomy.
  • The findings contribute to the knowledge of chromosomal abnormalities and their phenotypic consequences.
  • It provides definitive evidence that chromosome 1 is not subject to paternal imprinting in humans.

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