The maternal uniparental disomy of chromosome 6 (upd(6)mat) "phenotype": result of placental trisomy 6 mosaicism?

Mol Genet Genomic Med. 2017 Nov;5(6):668-677. doi: 10.1002/mgg3.324. Epub 2017 Sep 22.

Abstract

Background: Maternal uniparental disomy of chromosome 6 (upd(6)mat) is a rare finding and its clinical relevance is currently unclear. Based on clinical data from two new cases and patients from the literature, the pathogenetic significance of upd(6)mat is delineated.

Methods: Own cases were molecularly characterized for isodisomic uniparental regions on chromosome 6. For further cases with upd(6)mat, a literature search was conducted and genetic and clinical data were ascertained.

Results: Comparison of isodisomic regions between the new upd(6)mat cases and those from four reports did not reveal any common isodisomic region. Among the patients with available cytogenetic data, five had a normal karyotype in lymphocytes, whereas a trisomy 6 (mosaicism) was detected prenatally in four cases. A common clinical picture was not obvious in upd(6)mat, but intrauterine growth restriction (IUGR) and preterm delivery were frequent.

Conclusion: A common upd(6)mat phenotype is not obvious, but placental dysfunction due to trisomy 6 mosaicism probably contributes to IUGR and preterm delivery. In fact, other clinical features observed in upd(6)mat patients might be caused by homozygosity of recessive mutations or by an undetected trisomy 6 cell line. Upd(6)mat itself is not associated with clinical features, and can rather be regarded as a biomarker. In case upd(6)mat is detected, the cause for the phenotype is identified indirectly, but the UPD is not the basic cause.

Keywords: Chromosome 6; imprinting disorder; trisomic rescue; uniparental disomy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Chromosomes, Human, Pair 6*
  • Cullin Proteins / genetics
  • Female
  • Fetal Growth Retardation / diagnosis
  • Fetal Growth Retardation / genetics
  • Genetic Testing
  • Humans
  • Infant, Newborn
  • Karyotype
  • Male
  • Mosaicism
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Placenta / metabolism*
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Premature Birth
  • Steroid 21-Hydroxylase / genetics
  • Trisomy / diagnosis*
  • Trisomy / genetics
  • Uniparental Disomy / genetics
  • Uniparental Disomy / pathology*

Substances

  • Biomarkers
  • CUL7 protein, human
  • Cullin Proteins
  • CYP21A2 protein, human
  • Steroid 21-Hydroxylase