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

Abstract

Molecular analysis of a patient affected by the autosomal recessive skeletal dysplasia, pycnodysostosis (cathepsin K deficiency; MIM 265800), revealed homozygosity for a novel missense mutation (A277V). Since the A277V mutation was carried by the patient's father but not by his mother, who had two normal cathepsin K alleles, paternal uniparental disomy was suspected. Karyotyping of the patient and of both parents was normal, and high-resolution cytogenetic analyses of chromosome 1, to which cathepsin K is mapped, revealed no abnormalities. Evaluation of polymorphic DNA markers spanning chromosome 1 demonstrated that the patient had inherited two paternal chromosome 1 homologues, whereas alleles for markers from other chromosomes were inherited in a Mendelian fashion. The patient was homoallelic for informative markers mapping near the chromosome 1 centromere, but he was heteroallelic for markers near both telomeres, establishing that the paternal uniparental disomy with partial isodisomy was caused by a meiosis II nondisjunction event. Phenotypically, the patient had normal birth height and weight, had normal psychomotor development at age 7 years, and had only the usual features of pycnodysostosis. This patient represents the first case of paternal uniparental disomy of chromosome 1 and provides conclusive evidence that paternally derived genes on human chromosome 1 are not imprinted.

• Authors: B D Gelb, J P Willner, T M Dunn, N B Kardon, A Verloes, J Poncin, R J Desnick
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 62 Issue 4 Pg. 848-54 (Apr 1998) ISSN: 0002-9297 [Print] United States
• PMID: 9529353 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cathepsins
• CTSK protein, human
• Cathepsin K

Topics

• Adult
• Bone Diseases, Developmental (genetics)
• Cathepsin K
• Cathepsins (deficiency, genetics)
• Child, Preschool
• Chromosome Mapping
• Chromosomes, Human, Pair 1
• DNA Mutational Analysis
• Female
• Humans
• Male
• Mutation