High resolution snp based microarray mapping of mosaic supernumerary marker chromosomes 13 and 17

Delineating novel loci for apraxia

Jillene M. Kogan, Erin Miller, Stephanie Ware

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

High resolution comparative genomic hybridization is emerging as a powerful tool for delineating chromosomal rearrangements such as duplications, deletions, and unbalanced translocations, but it has not yet been broadly applied for structural aberrations such as supernumerary marker chromosomes (SMCs). In this report, we present the clinical and molecular analysis of a patient with de novo mosaic SMC (17) and SMC (13). High resolution single nucleotide polymorphism (SNP) based microarray mapping successfully identified the parent of origin for the SMCs and allowed delineation of the breakpoints which include a 5.1 Mb duplication from 17p11.2 to 17q11.2 as well as duplication of chromosome 13 that includes 2.2 Mb from 13q11 to 13q12.11. Interestingly, the patient has markedly severe oral and verbal apraxia, a characteristic feature of patients with 17p11.2 duplication syndrome (Potocki-Lupski syndrome, PTLS). Fine mapping indicates that the patient's duplication overlaps with a subset of PTLS patients, but not with PTLS patients harboring the common microduplication. FISH analysis confirms that the patient lacks duplication of RAI1, a dosage sensitive gene within the common microduplication interval. Taken together, these results demonstrate the utility of SNP microarray based methodology for mapping disease-causing genes, including those within SMCs, and provide the opportunity to identify novel candidate genes for verbal apraxia.

Original languageEnglish (US)
Pages (from-to)887-893
Number of pages7
JournalAmerican Journal of Medical Genetics, Part A
Volume149
Issue number5
DOIs
StatePublished - May 2009
Externally publishedYes

Fingerprint

Apraxias
Chromosomes, Human, Pair 13
Chromosomes, Human, Pair 17
Genetic Markers
Single Nucleotide Polymorphism
Comparative Genomic Hybridization
Gene Dosage
Genes
Potocki-Lupski syndrome

Keywords

  • 17p11.2 duplication syndrome
  • Comparative genomic hybridization
  • Snp microarray
  • Supernumerary marker chromosome
  • Verbal apraxia

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

High resolution snp based microarray mapping of mosaic supernumerary marker chromosomes 13 and 17 : Delineating novel loci for apraxia. / Kogan, Jillene M.; Miller, Erin; Ware, Stephanie.

In: American Journal of Medical Genetics, Part A, Vol. 149, No. 5, 05.2009, p. 887-893.

Research output: Contribution to journalArticle

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