Complex X-Chromosomal Rearrangements in Two Women with Ovarian Dysfunction

Implications of Chromothripsis/Chromoanasynthesis-Dependent and -Independent Origins of Complex Genomic Alterations

Erina Suzuki, Hirohito Shima, MacHiko Toki, Kunihiko Hanew, Keiko Matsubara, Hiroki Kurahashi, Satoshi Narumi, Tsutomu Ogata, Tsutomu Kamimaki, Maki Fukami

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Our current understanding of the phenotypic consequences and the molecular basis of germline complex chromosomal rearrangements remains fragmentary. Here, we report the clinical and molecular characteristics of 2 women with germline complex X-chromosomal rearrangements. Patient 1 presented with nonsyndromic ovarian dysfunction and hyperthyroidism; patient 2 exhibited various Turner syndrome- associated symptoms including ovarian dysfunction, short stature, and autoimmune hypothyroidism. The genomic abnormalities of the patients were characterized by array-based comparative genomic hybridization, high-resolution karyotyping, microsatellite genotyping, X-inactivation analysis, and bisulfite sequencing. Patient 1 carried a rearrangement of unknown parental origin with a 46,X,der(X)(pter→ p22.1::p11.23→q24::q21.3→q24::p11.4→pter) karyotype, indicative of a catastrophic chromosomal reconstruction due to chromothripsis/chromoanasynthesis. Patient 2 had a paternally derived isochromosome with a 46,X,der(X)(pter→ p22.31::q22.1→q10::q10→q22.1::p22.31→pter) karyotype, which likely resulted from 2 independent, sequential events. Both patients showed completely skewed X inactivation. CpG sites at Xp22.3 were hypermethylated in patient 2. The results indicate that germline complex X-chromosomal rearrangements underlie nonsyndromic ovarian dysfunction and Turner syndrome. Disease-causative mechanisms of these rearrangements likely include aberrant DNA methylation, in addition to X-chromosomal mispairing and haploinsufficiency of genes escaping X inactivation. Notably, our data imply that germline complex X-chromosomal rearrangements are created through both chromothripsis/chromoanasynthesis-dependent and -independent processes.

Original languageEnglish
Pages (from-to)86-92
Number of pages7
JournalCytogenetic and Genome Research
Volume150
Issue number2
DOIs
Publication statusPublished - 01-02-2017

Fingerprint

X Chromosome Inactivation
Turner Syndrome
Karyotype
Isochromosomes
Haploinsufficiency
Karyotyping
Comparative Genomic Hybridization
DNA Methylation
Hyperthyroidism
Chromothripsis
Microsatellite Repeats
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Suzuki, Erina ; Shima, Hirohito ; Toki, MacHiko ; Hanew, Kunihiko ; Matsubara, Keiko ; Kurahashi, Hiroki ; Narumi, Satoshi ; Ogata, Tsutomu ; Kamimaki, Tsutomu ; Fukami, Maki. / Complex X-Chromosomal Rearrangements in Two Women with Ovarian Dysfunction : Implications of Chromothripsis/Chromoanasynthesis-Dependent and -Independent Origins of Complex Genomic Alterations. In: Cytogenetic and Genome Research. 2017 ; Vol. 150, No. 2. pp. 86-92.
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Complex X-Chromosomal Rearrangements in Two Women with Ovarian Dysfunction : Implications of Chromothripsis/Chromoanasynthesis-Dependent and -Independent Origins of Complex Genomic Alterations. / Suzuki, Erina; Shima, Hirohito; Toki, MacHiko; Hanew, Kunihiko; Matsubara, Keiko; Kurahashi, Hiroki; Narumi, Satoshi; Ogata, Tsutomu; Kamimaki, Tsutomu; Fukami, Maki.

In: Cytogenetic and Genome Research, Vol. 150, No. 2, 01.02.2017, p. 86-92.

Research output: Contribution to journalArticle

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T2 - Implications of Chromothripsis/Chromoanasynthesis-Dependent and -Independent Origins of Complex Genomic Alterations

AU - Suzuki, Erina

AU - Shima, Hirohito

AU - Toki, MacHiko

AU - Hanew, Kunihiko

AU - Matsubara, Keiko

AU - Kurahashi, Hiroki

AU - Narumi, Satoshi

AU - Ogata, Tsutomu

AU - Kamimaki, Tsutomu

AU - Fukami, Maki

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