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PWS/AS MS-MLPA Confirms Maternal Origin of 15q11.2 Microduplication
Angelika J Dawson1, Janice Cox2, Karine Hovanes3
1Cytogenetic Laboratory, HSC, Diagnostic Services of Manitoba, 820 Sherbrook Street, Winnipeg, MB, Canada R3A 1K9 ; Departments of Biochemistry & Medical Genetics and Pediatrics & Child Health, University of Manitoba, Winnipeg, MB, Canada R3E 0J9 ; Genetics & Metabolism Program, WRHA, Winnipeg, MB, Canada R3A 1R9.
Abstract:
The proximal region of the long arm of chromosome 15q11.2-q13 is associated with various neurodevelopmental disorders, including Prader-Willi (PWS) and Angelman (AS) syndromes, autism, and other developmental abnormalities resulting from deletions and duplications. In addition, this region encompasses imprinted genes that cause PWS or AS, depending on the parent-of-origin. This imprinting allows for diagnosis of PWS or AS based on methylation status using methylation sensitive (MS) multiplex ligation dependent probe amplification (MLPA). Maternally derived microduplications at 15q11.2-q13 have been associated with autism and other neuropsychiatric disorders. Multiple methods have been used to determine the parent-of-origin for 15q11.2-q13 microdeletions and microduplications. In the present study, a four-year-old nondysmorphic female patient with developmental delay was found to have a de novo ~5 Mb duplication within 15q11.2 by oligonucleotide genomic array. In order to determine the significance of this microduplication to the clinical phenotype, the parent-of-origin needed to be identified. The PWS/AS MS-MLPA assay is generally used to distinguish between deletion and uniparental disomy (UPD) of 15q11.2-q13, resulting in either PWS or AS. However, our study shows that PWS/AS MS-MLPA can also efficiently distinguish the parental origin of duplications of 15q11.2-q13.
Insights
Methylation sensitive multiplex ligation dependent probe amplification (MS-MLPA) can identify the parental origin of chromosome 15 duplications. This method aids in diagnosing neurodevelopmental disorders linked to 15q11.2-q13 duplications.
Area of Science:
- Genetics
- Neurodevelopmental Disorders
- Molecular Diagnostics
Background:
- The 15q11.2-q13 region is implicated in neurodevelopmental disorders like Prader-Willi Syndrome (PWS) and Angelman Syndrome (AS) due to deletions and duplications.
- Genomic imprinting in this region determines PWS or AS based on parental origin.
- Maternally inherited microduplications at 15q11.2-q13 are associated with autism and neuropsychiatric conditions.
Purpose of the Study:
- To determine the clinical significance of a de novo 15q11.2 microduplication in a patient with developmental delay.
- To evaluate the utility of the PWS/AS MS-MLPA assay in identifying the parental origin of 15q11.2-q13 microduplications.
Main Methods:
- Oligonucleotide genomic array to detect a de novo ~5 Mb duplication within 15q11.2.
- Methylation sensitive (MS) multiplex ligation dependent probe amplification (MLPA) PWS/AS assay to determine parental origin.
Main Results:
- A de novo ~5 Mb duplication in the 15q11.2 region was identified in a pediatric patient with developmental delay.
- The PWS/AS MS-MLPA assay successfully distinguished the parental origin of the 15q11.2-q13 microduplication.
Conclusions:
- The PWS/AS MS-MLPA assay is an effective tool for determining the parental origin of microduplications in the 15q11.2-q13 region.
- This diagnostic capability is crucial for understanding the genetic basis of neurodevelopmental disorders associated with this chromosomal region.
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