A female patient with retinoblastoma and severe intellectual disability carrying an X;13 balanced translocation without rearrangement in the RB1 gene: A case report

Makiko Tsutsumi, Hiroyoshi Hattori, Nobuhiro Akita, Naoko Maeda, Toshinobu Kubota, Keizo Horibe, Naoko Fujita, Miki Kawai, Yasuko Shinkai, Maki Kato, Takema Kato, Rie Kawamura, Fumihiko Suzuki, Hiroki Kurahashi

Research output: Contribution to journalArticle

Abstract

Background: Female carriers of a balanced X; autosome translocation generally undergo selective inactivation of the normal X chromosome. This is because inactivation of critical genes within the autosomal region of the derivative translocation chromosome would compromise cellular function. We here report a female patient with bilateral retinoblastoma and a severe intellectual disability who carries a reciprocal X-autosomal translocation. Case presentation: Cytogenetic and molecular analyses, a HUMARA (Human androgen receptor) assay, and methylation specific PCR (MSP) and bisulfite sequencing were performed using peripheral blood samples from the patient. The patient's karyotype was 46,X,t(X;13)(q28;q14.1) by G-banding analysis. Further cytogenetic analysis located the entire RB1 gene and its regulatory region on der(X) with no translocation disruption. The X-inactivation pattern in the peripheral blood was highly skewed but not completely selected. MSP and deep sequencing of bisulfite-treated DNA revealed that an extensive 13q region, including the RB1 promoter, was unusually methylated in a subset of cells. Conclusions: The der(X) region harboring the RB1 gene was inactivated in a subset of somatic cells, including the retinal cells, in the patient subject which acted as the first hit in the development of her retinoblastoma. In addition, the patient's intellectual disability may be attributable to the inactivation of the der(X), leading to a 13q deletion syndrome-like phenotype, or to an active X-linked gene on der (13) leading to Xq28 functional disomy.

Original languageEnglish
Article number182
JournalBMC Medical Genomics
Volume12
Issue number1
DOIs
Publication statusPublished - 05-12-2019

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Retinoblastoma
Intellectual Disability
X Chromosome Inactivation
Genes
Cytogenetic Analysis
Methylation
High-Throughput Nucleotide Sequencing
Polymerase Chain Reaction
X-Linked Genes
Nucleic Acid Regulatory Sequences
Gene Silencing
Karyotype
Chromosomes
Phenotype
DNA

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Tsutsumi, Makiko ; Hattori, Hiroyoshi ; Akita, Nobuhiro ; Maeda, Naoko ; Kubota, Toshinobu ; Horibe, Keizo ; Fujita, Naoko ; Kawai, Miki ; Shinkai, Yasuko ; Kato, Maki ; Kato, Takema ; Kawamura, Rie ; Suzuki, Fumihiko ; Kurahashi, Hiroki. / A female patient with retinoblastoma and severe intellectual disability carrying an X;13 balanced translocation without rearrangement in the RB1 gene : A case report. In: BMC Medical Genomics. 2019 ; Vol. 12, No. 1.
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A female patient with retinoblastoma and severe intellectual disability carrying an X;13 balanced translocation without rearrangement in the RB1 gene : A case report. / Tsutsumi, Makiko; Hattori, Hiroyoshi; Akita, Nobuhiro; Maeda, Naoko; Kubota, Toshinobu; Horibe, Keizo; Fujita, Naoko; Kawai, Miki; Shinkai, Yasuko; Kato, Maki; Kato, Takema; Kawamura, Rie; Suzuki, Fumihiko; Kurahashi, Hiroki.

In: BMC Medical Genomics, Vol. 12, No. 1, 182, 05.12.2019.

Research output: Contribution to journalArticle

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T1 - A female patient with retinoblastoma and severe intellectual disability carrying an X;13 balanced translocation without rearrangement in the RB1 gene

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AU - Tsutsumi, Makiko

AU - Hattori, Hiroyoshi

AU - Akita, Nobuhiro

AU - Maeda, Naoko

AU - Kubota, Toshinobu

AU - Horibe, Keizo

AU - Fujita, Naoko

AU - Kawai, Miki

AU - Shinkai, Yasuko

AU - Kato, Maki

AU - Kato, Takema

AU - Kawamura, Rie

AU - Suzuki, Fumihiko

AU - Kurahashi, Hiroki

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Y1 - 2019/12/5

N2 - Background: Female carriers of a balanced X; autosome translocation generally undergo selective inactivation of the normal X chromosome. This is because inactivation of critical genes within the autosomal region of the derivative translocation chromosome would compromise cellular function. We here report a female patient with bilateral retinoblastoma and a severe intellectual disability who carries a reciprocal X-autosomal translocation. Case presentation: Cytogenetic and molecular analyses, a HUMARA (Human androgen receptor) assay, and methylation specific PCR (MSP) and bisulfite sequencing were performed using peripheral blood samples from the patient. The patient's karyotype was 46,X,t(X;13)(q28;q14.1) by G-banding analysis. Further cytogenetic analysis located the entire RB1 gene and its regulatory region on der(X) with no translocation disruption. The X-inactivation pattern in the peripheral blood was highly skewed but not completely selected. MSP and deep sequencing of bisulfite-treated DNA revealed that an extensive 13q region, including the RB1 promoter, was unusually methylated in a subset of cells. Conclusions: The der(X) region harboring the RB1 gene was inactivated in a subset of somatic cells, including the retinal cells, in the patient subject which acted as the first hit in the development of her retinoblastoma. In addition, the patient's intellectual disability may be attributable to the inactivation of the der(X), leading to a 13q deletion syndrome-like phenotype, or to an active X-linked gene on der (13) leading to Xq28 functional disomy.

AB - Background: Female carriers of a balanced X; autosome translocation generally undergo selective inactivation of the normal X chromosome. This is because inactivation of critical genes within the autosomal region of the derivative translocation chromosome would compromise cellular function. We here report a female patient with bilateral retinoblastoma and a severe intellectual disability who carries a reciprocal X-autosomal translocation. Case presentation: Cytogenetic and molecular analyses, a HUMARA (Human androgen receptor) assay, and methylation specific PCR (MSP) and bisulfite sequencing were performed using peripheral blood samples from the patient. The patient's karyotype was 46,X,t(X;13)(q28;q14.1) by G-banding analysis. Further cytogenetic analysis located the entire RB1 gene and its regulatory region on der(X) with no translocation disruption. The X-inactivation pattern in the peripheral blood was highly skewed but not completely selected. MSP and deep sequencing of bisulfite-treated DNA revealed that an extensive 13q region, including the RB1 promoter, was unusually methylated in a subset of cells. Conclusions: The der(X) region harboring the RB1 gene was inactivated in a subset of somatic cells, including the retinal cells, in the patient subject which acted as the first hit in the development of her retinoblastoma. In addition, the patient's intellectual disability may be attributable to the inactivation of the der(X), leading to a 13q deletion syndrome-like phenotype, or to an active X-linked gene on der (13) leading to Xq28 functional disomy.

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