October 2020 — Laboratory Genetics and Genomics

Multiplex ligation-dependent probe amplification (MLPA) testing on a female for Prader Willi/ Angelman syndrome indicates a copy number state double the norm for the critical region with methylation specific probes at a copy number state of approximatly 3 (Figs A and B). There is no clinical phenotype information from the ordering provider.

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What is the best explanation for this unusual pattern?

  • 47,XX,+psu idic(15)(q13.3)mat
  • 47,XX,+ 15/46,XX (mosaic trisomy 15, extra copy is paternal in origen)
  • 47,XX,+psu idic(15)(q13.3)pat
  • 46,XX dup(15)(q11.2-q11.3) (duplication in critical region on maternal allele)

The correct answer is...

The correct answer is 47,XX,+psu idic(15)(q13.3)mat.

Since the copy state at this genomic locus is 4, there must be two additional copies of this region. Since the methylated probe copy state is falling at three, we can infer that three of these copies are methylated and therefore maternally derived.

The MLPA test for Prader Willi / Angeman Synrome only includes probes located in the critical region. However, the best explanation for such an unusual pattern is a pseudoisodicentric 15q arm of maternal origin.

This abnormality is rare but has been reported in the literature in connection with dysmorphic features, intellectual disability, growth deficiency, triangular facies, and brachydactyly [1]. Patients with idic (15) of paternal origin seem to have normal development.


References
1. Szabo A, Czako M, Hadzsiev K, Duga B, Komlosi K, Melegh B. Partial tetrasomy of the proximal long arm of chromosome 15 in two patients: the significance of the gene dosage in terms of phenotype. Mol Cytogenet. 2015;8:41.

Photo of Jaime Lopes, Ph.D. Jaime Lopes, Ph.D.
Resident, Laboratory Genetics and Genomics
Mayo Clinic
Photo of Linda Hasadsri, M.D., Ph.D Linda Hasadsri, M.D., Ph.D.
Consultant, Laboratory Genetics and Genomicsy
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
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This post was developed by our Education and Technical Publications Team.