15q11.2 Duplication, FISH
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Cytogenetic abnormalities at the 15q11-q13 locus are reported in up to 4% of patients with autism spectrum disorders. Duplications in this chromosome region can occur as an interstitial tandem repeat or as a supernumerary isodicentric chromosome 15, leading to trisomy or tetrasomy of genes at the 15q11-q13 locus. The majority of interstitial tandem repeats in this region are not detectable by conventional chromosome analysis but can be identified by FISH. Supernumerary chromosomes can often be identified by conventional chromosome analysis but their origin must be confirmed by FISH analysis. Molecular analysis by multiplex ligation-dependent probe amplification can also detect duplications of chromosome 15q, but FISH analysis is necessary to distinguish between interstitial tandem duplication and a supernumerary marker.
The phenotype associated with these abnormalities depends largely on the amount of duplicated material, as well as parent of origin. Small dicentric markers with little 15q material duplicated are often familial and result in a normal phenotype. Larger dicentric 15 markers are usually new mutations and result in mild dysmorphic features, mental retardation, and behavioral abnormalities consistent with autism. Interstitial tandem duplications are associated with autistic spectrum disorders when maternally inherited, but paternally inherited duplications are less likely to cause phenotypic effects.
Detecting duplications of the 15q11.1-11.3 region in individuals with autistic spectrum disorders
As an adjunct to conventional chromosome analysis to confirm the origin of supernumerary marker chromosomes suspected of being derived from chromosome 15
To help resolve molecular multiplex ligation-dependent probe amplification analysis where 15q duplication is identified, but the structural origin of the duplication is unknown
Specimens with a normal signal pattern in metaphase and interphase cells are considered negative for this probe.
Specimens with a FISH signal pattern indicating duplication of the critical region (3 signals) will be reported as having a duplication of the region tested by this probe.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Because this FISH assay is not approved by the FDA, it is important to correlate 15q duplications by other established methods, such as clinical history or physical evaluation.
This test is not designed to identify 15q deletions or diagnose Prader-Willi/Angelman syndromes. The most appropriate test to identify 15q deletions or diagnose Prader-Willi/Angelman syndromes is PWDNA / Prader-Willi/Angelman Syndrome, Molecular Analysis.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretative report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Mao R, Jalal SM, Snow K, et al: Characteristics of two cases with dup(15)(q11.2-q12): one of maternal and one of paternal origin. Genet Med 2000;2:131-135
2. Thomas JA, Johnson J, Peterson Kraai TL, et al: Genetic and clinical characterization of patients with an interstitial duplication 15q11-q13, emphasizing behavioral phenotype and response to treatment. Am J Med Genet 2003;119:111-120
3. Battaglia A: The inv dup(15) or idic(15) syndrome: a clinically recognizable neurogenetic disorder. Brain Dev 2005;5:365-369
4. Muhle R, Trentacoste S, Rapin I: The genetics of autism. Pediatrics 2004;113:472-486