Test ID: UNIPD    
Uniparental Disomy, Varies

Evaluation of patients presenting with mosaicism, confined placental mosaicism, or Robertsonian translocations

Evaluation of patients presenting with features of disorders known to be associated with uniparental disomy (eg, Russell-Silver syndrome)

Evaluation of disease mechanism in individuals with rare autosomal recessive disease and only one carrier parent

Samples from fetus or child and both parents are required for analysis. Chromosome of interest must be specified on request form.

Polymerase chain reaction (PCR) and microsatellite markers on the chromosome of interest are used to test DNA from the parents and the child for the presence of uniparental disomy. Uniparental disomy testing is available for all chromosomes, with the exception of chromosome 11 for certain indications. Contact the laboratory for additional information.

For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added and charged separately. If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added and charged separately.

See Prader-Willi and Angelman Syndromes: Laboratory Approach to Diagnosis algorithm in Special Instructions.

Uniparental disomy (UPD) occurs when a child inherits 2 copies of a chromosome from 1 parent and no copies of that chromosome from the other parent. This error in division occurs during the formation of egg or sperm cells (meiosis). When an error causing UPD occurs during meiosis I both chromosome homologs from a single parent are transmitted, and heterodisomy results. When the error causing UPD occurs during meiosis II or as a postzygotic event, and a single parental homolog is transmitted to offspring in duplicate, isodisomy results. Meiotic recombination events within the context of UPD often result in a mixture of heterodisomy and isodisomy. UPD can involve an entire chromosome or only a segment. Mosaicism for UPD also occurs in combination with either chromosomally normal or abnormal cell lines.

When UPD occurs, the imbalance of maternal versus paternal genetic information for the involved chromosome can be associated with clinical symptoms in the affected child. UPD does not always impart an abnormal clinical phenotype however. In fact, while isodisomy can result in disease due to a recessive allele at any location, heterodisomy is not expected to result in an abnormal clinical phenotype unless the involved chromosome or chromosomal segment includes imprinted genes. Imprinted genes demonstrate differential expression depending on parent of origin. Disorders that result from UPD of imprinted genes are not due to a defect in the imprinting mechanism itself, but rather they are due to an unbalanced parental contribution of normally imprinted alleles that results in altered expression of imprinted genes. For example, when maternal UPD 15 occurs (2 copies of the maternal chromosome 15 instead of 1 maternal and 1 paternal copy of chromosome 15), it causes Prader-Willi syndrome due to the lack of paternally expressed genes at the imprinted site.

UPD has been described for many but not all chromosomes. In addition to the rare cases of autosomal recessive disease that result from isodisomy, clinical syndromes associated with UPD have been described for only a few chromosomes, including Russell-Silver syndrome (UPD 7), Prader-Willi syndrome (UPD 15), Angelman syndrome (UPD 15), transient neonatal diabetes (UPD 6), and UPD of chromosome14.

UPD cannot be identified by gross cytogenetic analysis and requires DNA-based analysis using multiple polymorphic markers spanning the chromosome of interest. Specimens from both parents and the child or fetus are required.

An interpretive report will be provided.

An interpretative report will be provided.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

This test will detect nonpaternity.

Uniparental disomy (UPD) may not be detected by our assay in cases where there is low-level mosaicism for a particular chromosome.

Although UPD testing is available for all chromosomes, prenatal testing for UPD for chromosomes other than those associated with known phenotypes should be done only after genetic counseling involving adequate discussion of risks, benefits, and limitations of testing.

1. Schaffer LG, Agan N, Goldberg JD, et al: American College of Medical Genetics statement on diagnostic testing for uniparental disomy. Genet Med. 2001;3:206-211

2. Kotzot D, Utermann G: Uniparental Disomy (UPD) other than 15: phenotypes and bibliography updated. Am J Med Genet. 2005;136A:287-305

3. Kotzot D: Prenatal testing for uniparental disomy: indications and clinical relevance. Ultrasound Obstet Gynecol. 2008:31:100-105

4. Engel E: A fascination with chromosome rescue in uniparental disomy: Mendelian recessive outlaws and imprinting copyrights infringements. Eur J Hum Genet. 2006 Nov;14(11):1158-1169

• Molecular Genetics: Congenital Inherited Diseases Patient Information
• Informed Consent for Genetic Testing
• Prader-Willi and Angelman Syndromes: Laboratory Approach to Diagnosis
• Informed Consent for Genetic Testing (Spanish)