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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

PLP1 duplication at the breakpoint regions of an apparently balanced t(X;22) translocation causes Pelizaeus-Merzbacher disease in a girl

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Fonseca, A. C. S. ; Bonaldi, A. ; Costa, S. S. ; Freitas, M. R. [1] ; Kok, F. [1] ; Vianna-Morgante, A. M. [2]
Total Authors: 6
[1] Univ Sao Paulo, Fac Med, Dept Neurol, BR-05508090 Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Fac Med, BR-05508090 Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Clinical Genetics; v. 83, n. 2, p. 169-174, FEB 2013.
Web of Science Citations: 7

Fonseca ACS, Bonaldi A, Costa SS, Freitas MR, Kok F, Vianna-Morgante AM. PLP1 duplication at the breakpoint regions of an apparently balanced t(X;22) translocation causes PelizaeusMerzbacher disease in a girl. PLP1 (proteolipid protein1 gene) mutations cause PelizaeusMerzbacher disease (PMD), characterized by hypomyelination of the central nervous system, and affecting almost exclusively males. We report on a girl with classical PMD who carries an apparently balanced translocation t(X;22)(q22;q13). By applying array-based comparative genomic hybridization (a-CGH), we detected duplications at 22q13 and Xq22, encompassing 487546 kb and 543611 kb, respectively. The additional copies were mapped by fluorescent in situ hybridization to the breakpoint regions, on the derivative X chromosome (22q13 duplicated segment) and on the derivative 22 chromosome (Xq22 duplicated segment). One of the 14 duplicated X-chromosome genes was PLP1.The normal X chromosome was the inactive one in the majority of peripheral blood leukocytes, a pattern of inactivation that makes cells functionally balanced for the translocated segments. However, a copy of the PLP1 gene on the derivative chromosome 22, in addition to those on the X and der(X) chromosomes, resulted in two active copies of the gene, irrespective of the X-inactivation pattern, thus causing PMD. This t(X;22) is the first constitutional human apparently balanced translocation with duplications from both involved chromosomes detected at the breakpoint regions. (AU)

FAPESP's process: 09/03480-8 - Characterization of apparently balanced chromosomal rearrangements associated with clinical phenotypes: breakpoint mapping and screening for submicroscopic deletions and duplications
Grantee:Ana Carolina dos Santos Fonseca
Support type: Scholarships in Brazil - Master
FAPESP's process: 98/14254-2 - The Human Genome Research Center
Grantee:Mayana Zatz
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 09/00898-1 - Submicroscopic genomic imbalances associated with specific congenital abnormalities and mental deficiency phenotypes
Grantee:Carla Rosenberg
Support type: Research Projects - Thematic Grants