Genomic + clinical characteristics of microduplications in chromosome 17

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Am J Med Genet A. 2010 May;152A(5):1101-10.

Genomic and clinical characteristics of microduplications in chromosome 17.

Shchelochkov OA, Cheung SW, Lupski JR.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston,

TX 77050, USA.

Abstract

Genomic disorders have been increasingly recognized as a significant source of

clinically relevant phenotypes largely fostered by advances in technologies for

genome-wide analyses. Molecular and clinical studies of copy number variants

involving chromosome 17 began with locus-specific studies of Charcot-Marie-Tooth

disease type 1A (CMT1A, OMIM #118220) and hereditary neuropathy with liability

to pressure palsies (HNPP, OMIM #162500), which laid the foundation for the

paradigm of duplication/deletion and gene-dosage for our understanding of

genomic disorders.

With the clinical introduction of high-resolution array comparative genomic

hybridization (aCGH) the number of recognized genomic disorders including

microduplications has been increasing rapidly. A relatively high proportion of

disease-associated copy number variants map to chromosome 17.

This may result from its unique structural features, such as relative abundance

of segmental duplications and interspersed repetitive elements, high gene

content, and the presence of dosage-sensitive genes.

These genomic rearrangements are mediated by diverse mechanisms including

Non-Allelic Homologous Recombination (NAHR), Non-Homologous End-Joining (NHEJ),

and Fork Stalling and Template Switching (FoSTeS).

We provide specific examples of chromosome 17 microduplications with the

emphasis on their phenotype, specific clinical features aiding in their

diagnosis, and counseling.