CMT 1A: Evidence for involvement of TRE-2 (USP6) oncogene, low-copy repeat and a

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Hum Genet. 2006 Jun 22

Evidence for involvement of TRE-2 (USP6) oncogene, low-copy repeat

and acrocentric heterochromatin in two families with chromosomal

translocations.

Ou Z, Jarmuz M, Sparagana SP, Michaud J, Decarie JC, Yatsenko SA,

Nowakowska B, Furman P, Shaw CA, Shaffer LG, Lupski JR, Chinault AC,

Cheung SW, Stankiewicz P.

Department of Molecular & Human Genetics, Baylor College of Medicine,

One Baylor Plaza, Rm. T821, Houston, TX, 77030, USA.

We report clinical findings and molecular cytogenetic analyses for

two patients with translocations [t(14;17)(p12;p12) and t(15;17)

(p12;p13.2)], in which the chromosome 17 breakpoints map at a large

low-copy repeat (LCR) and a breakage-prone TRE-2 (USP6) oncogene,

respectively. In family 1, a 6-year-old girl and her 5-year-old

brother were diagnosed with mental retardation, short stature,

dysmorphic features, and Charcot-Marie-Tooth disease type 1A (CMT1A).

G-banding chromosome analysis showed a der(14)t(14;17)(p12;p12) in

both siblings, inherited from their father, a carrier of the balanced

translocation. Chromosome microarray and FISH analyses revealed that

the PMP22 gene was duplicated. The chromosome 17 breakpoint was

mapped within an approximately 383 kb LCR17pA that is known to also

be the site of several breakpoints of different chromosome

aberrations including the evolutionary translocation t(4;19) in

Gorilla gorilla.

In family two, a patient with developmental delay, subtle dysmorphic

features, ventricular enlargement with decreased periventricular

white matter, mild findings of bilateral perisylvian polymicrogyria

and a very small anterior commissure, a cryptic duplication including

the -Dieker syndrome region was identified by chromosome

microarray analysis. The chromosome 17 breakpoint was mapped by FISH

at the TRE-2 oncogene. Both partner chromosome breakpoints were

mapped on the short arm acrocentric heterochromatin within or distal

to the rRNA cluster, distal to the region commonly rearranged in

onian translocations.

We propose that TRE-2 together with LCR17pA, located approximately 10

Mb apart, also generated the evolutionary gorilla translocation t

(4;19). Our results support previous observations that the USP6

oncogene, LCRs, and repetitive DNA sequences play a significant role

in the origin of constitutional chromosome aberrations and primate

genome evolution.