Rhizomelic chrondrodysplasia punctata type 2 resulting from paternal isodisomy of chromosome 1

Graeme Nimmo, Sarah Monsonego, Maria Descartes, Judith Franklin, Steven Steinberg, Nancy Braverman

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Rhizomelic chondrodysplasia punctata (RCDP) is an autosomalrecessive disorder resulting from mutations in one of three peroxisomal genes essential for ether lipid biosynthesis, PEX7 (RCDP1), GNPAT (RCDP2), and AGPS (RCDP3). Affected patients have characteristic features including shortening of the proximal long bones, epiphyseal stippling, bilateral cataracts, growth and developmental delays. Whereas the majority of patients have RCDP type 1, around 5% have RCDP type 2 or 3. We identified a patient with RCDP type 2 and an apparent homozygous deletion, c.1428delC, after full sequencing of his GNPAT genes. The father was heterozygous for this mutation, while sequencing of the maternal GNPAT genes revealed only wild-type sequence. Southern analyses performed on parental gDNA did not show evidence of a maternal gene deletion. Amplification and fragment analysis of dinucleotide repeat markers spanning chromosome 1 in the patient and both parents revealed paternal uniparental inheritance. We discuss the potential mechanisms causing uniparental disomy (UPD) in this patient and review the literature on chromosome 1 UPD. The absence of non-RCDP clinical features in this patient was consistent with previous literature supporting the absence of imprinted genes on chromosome 1. This first description of RCDP caused by UPD dramatically changes the parental recurrence risk, highlighting the value of obtaining parental genotypes when the proband has a putative homozygous mutation by sequence analysis.

Original languageEnglish (US)
Pages (from-to)1812-1817
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Issue number7
StatePublished - Jul 2010
Externally publishedYes


  • Peroxisome disorder
  • Rhizomelic chondrodysplasia punctata
  • Uniparental disomy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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