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

Autor(es)

Fonseca, A. C. S. ; Bonaldi, A. ; Costa, S. S. ; Freitas, M. R. ^[1] ; Kok, F. ^[1] ; Vianna-Morgante, A. M. ^[2]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Clinical Genetics; v. 83, n. 2, p. 169-174, FEB 2013.
• Citações Web of Science: 7

Resumo

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)

• Processo FAPESP: 09/03480-8 - Caracterização de rearranjos cromossômicos aparentemente equilibrados associados a quadros clínicos: mapeamento dos pontos de quebra e triagem de deleções e duplicações submicroscópicas
• Beneficiário: Ana Carolina dos Santos Fonseca
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 09/00898-1 - Desequilíbrios genômicos submicroscópicos em quadros clínicos específicos de anomalias congênitas e deficiência mental
• Beneficiário: Carla Rosenberg
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 98/14254-2 - Centro de Estudos do Genoma Humano
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs