Co-occurrence of recurrent duplications of the digeorge syndrome region on both chromosome 22 homologues due to inherited and de novo events

Weimin Bi, Frank J. Probst, Joanna Wiszniewska, Katie Plunkett, Erin K. Roney, Brian S. Carter, Misti D. Williams, Pawel Stankiewicz, Ankita Patel, Cathy A. Stevens, James R. Lupski, Sau Wai Cheung

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Genomic rearrangements usually involve one of the two chromosome homologues. Homozygous microdeletion/duplication is very rare. The chromosome 22q11.2 region is prone to recurrent rearrangements due to the presence of low-copy repeats. A common 3 Mb microdeletion causes the well-characterised DiGeorge syndrome (DGS). The reciprocal duplication is associated with an extremely variable phenotype, ranging from apparently normal to learning disabilities and multiple congenital anomalies. Methods and results: We describe duplications of the DGS region on both homologues in five patients from three families, detected by array CGH and confirmed by both fluorescence in situ hybridisation and single nucleotide polymorphism arrays. The proband in the first family is homozygous for the common duplication; one maternally inherited and the other a de novo duplication that was generated by nonallelic homologous recombination during spermatogenesis. The 22q11.2 duplications in the four individuals from the other two families are recurrent duplications on both homologues, one inherited from the mother and the other from the father. The phenotype in the patients with a 22q11.2 tetrasomy is similar to the features seen in duplication patients, including cognitive deficits and variable congenital defects. Conclusions: Our studies that reveal phenotypic variability in patients with four copies of the 22q11.2 genomic segment, demonstrate that both inherited and de novo events can result in the generation of homozygous duplications, and further document how multiple seemingly rare events can occur in a single individual.

Original languageEnglish (US)
Pages (from-to)681-688
Number of pages8
JournalJournal of Medical Genetics
Volume49
Issue number11
DOIs
StatePublished - Nov 1 2012
Externally publishedYes

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DiGeorge Syndrome
Chromosomes, Human, Pair 22
Tetrasomy
Chromosomes
Genomic Segmental Duplications
Phenotype
Learning Disorders
Homologous Recombination
Spermatogenesis
Fluorescence In Situ Hybridization
Fathers
Single Nucleotide Polymorphism
Mothers

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Co-occurrence of recurrent duplications of the digeorge syndrome region on both chromosome 22 homologues due to inherited and de novo events. / Bi, Weimin; Probst, Frank J.; Wiszniewska, Joanna; Plunkett, Katie; Roney, Erin K.; Carter, Brian S.; Williams, Misti D.; Stankiewicz, Pawel; Patel, Ankita; Stevens, Cathy A.; Lupski, James R.; Cheung, Sau Wai.

In: Journal of Medical Genetics, Vol. 49, No. 11, 01.11.2012, p. 681-688.

Research output: Contribution to journalArticle

Bi, W, Probst, FJ, Wiszniewska, J, Plunkett, K, Roney, EK, Carter, BS, Williams, MD, Stankiewicz, P, Patel, A, Stevens, CA, Lupski, JR & Cheung, SW 2012, 'Co-occurrence of recurrent duplications of the digeorge syndrome region on both chromosome 22 homologues due to inherited and de novo events', Journal of Medical Genetics, vol. 49, no. 11, pp. 681-688. https://doi.org/10.1136/jmedgenet-2012-101002
Bi, Weimin ; Probst, Frank J. ; Wiszniewska, Joanna ; Plunkett, Katie ; Roney, Erin K. ; Carter, Brian S. ; Williams, Misti D. ; Stankiewicz, Pawel ; Patel, Ankita ; Stevens, Cathy A. ; Lupski, James R. ; Cheung, Sau Wai. / Co-occurrence of recurrent duplications of the digeorge syndrome region on both chromosome 22 homologues due to inherited and de novo events. In: Journal of Medical Genetics. 2012 ; Vol. 49, No. 11. pp. 681-688.
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AU - Probst, Frank J.

AU - Wiszniewska, Joanna

AU - Plunkett, Katie

AU - Roney, Erin K.

AU - Carter, Brian S.

AU - Williams, Misti D.

AU - Stankiewicz, Pawel

AU - Patel, Ankita

AU - Stevens, Cathy A.

AU - Lupski, James R.

AU - Cheung, Sau Wai

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