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Rhizomelic chrondrodysplasia punctata type 2 resulting from paternal isodisomy of chromosome 1
- Source :
- American Journal of Medical Genetics Part A. :1812-1817
- Publication Year :
- 2010
- Publisher :
- Wiley, 2010.
-
Abstract
- Rhizomelic chondrodysplasia punctata (RCDP) is an autosomal-recessive 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.
- Subjects :
- Male
Proband
DNA Mutational Analysis
Molecular Sequence Data
Limb Deformities, Congenital
Uniparental inheritance
Biology
medicine.disease_cause
Fathers
Pregnancy
Peroxisomal disorder
Genetics
medicine
Humans
Chondrodysplasia punctata
Genetics (clinical)
Mutation
Rhizomelic chondrodysplasia punctata
Base Sequence
Chondrodysplasia Punctata, Rhizomelic
Infant, Newborn
Infant
Uniparental Disomy
medicine.disease
Uniparental disomy
Pedigree
Radiography
Chromosomes, Human, Pair 1
Female
Genomic imprinting
Hand Deformities, Congenital
Subjects
Details
- ISSN :
- 15524833 and 15524825
- Database :
- OpenAIRE
- Journal :
- American Journal of Medical Genetics Part A
- Accession number :
- edsair.doi.dedup.....e62fa234df9a003189aad607fa7d8e92