دورية أكاديمية
أعرض في EDS

Position effect, cryptic complexity, and direct gene disruption as disease mechanisms in de novo apparently balanced translocation cases.

التفاصيل البيبلوغرافية
العنوان: Position effect, cryptic complexity, and direct gene disruption as disease mechanisms in de novo apparently balanced translocation cases.
المؤلفون: Aristidou C; Department of Cytogenetics and Genomics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.; The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus., Theodosiou A; Department of Cytogenetics and Genomics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus., Bak M; Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen N., Denmark., Mehrjouy MM; Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen N., Denmark., Constantinou E; Department of Cytogenetics and Genomics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus., Alexandrou A; Department of Cytogenetics and Genomics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus., Papaevripidou I; Department of Cytogenetics and Genomics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus., Christophidou-Anastasiadou V; Department of Clinical Genetics, The Cyprus Institute of Neurology and Genetics and Archbishop Makarios III Medical Centre, Nicosia, Cyprus., Skordis N; Division of Pediatric Endocrinology, Paedi Center for Specialized Pediatrics, Nicosia, Cyprus.; St George's University of London Medical School at the University of Nicosia, Nicosia, Cyprus., Kitsiou-Tzeli S; Department of Medical Genetics, Medical School, University of Athens, Athens, Greece., Tommerup N; Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen N., Denmark., Sismani C; Department of Cytogenetics and Genomics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.; The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
المصدر: PloS one [PLoS One] 2018 Oct 05; Vol. 13 (10), pp. e0205298. Date of Electronic Publication: 2018 Oct 05 (Print Publication: 2018).
نوع المنشور: Case Reports; Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Facies* , Translocation, Genetic*, Hearing Loss/*genetics , Intellectual Disability/*genetics , Language Development Disorders/*genetics, Base Sequence ; Chromosome Breakpoints ; Female ; Gene Expression ; Hearing Loss/diagnosis ; Hearing Loss/physiopathology ; Humans ; Intellectual Disability/diagnosis ; Intellectual Disability/physiopathology ; Karyotype ; Language Development Disorders/diagnosis ; Language Development Disorders/physiopathology ; NFI Transcription Factors/deficiency ; NFI Transcription Factors/genetics ; POU Domain Factors/deficiency ; POU Domain Factors/genetics ; Phenotype ; SOXD Transcription Factors/deficiency ; SOXD Transcription Factors/genetics ; Whole Genome Sequencing
مستخلص: The majority of apparently balanced translocation (ABT) carriers are phenotypically normal. However, several mechanisms were proposed to underlie phenotypes in affected ABT cases. In the current study, whole-genome mate-pair sequencing (WG-MPS) followed by Sanger sequencing was applied to further characterize de novo ABTs in three affected individuals. WG-MPS precisely mapped all ABT breakpoints and revealed three possible underlying molecular mechanisms. Firstly, in a t(X;1) carrier with hearing loss, a highly skewed X-inactivation pattern was observed and the der(X) breakpoint mapped ~87kb upstream an X-linked deafness gene namely POU3F4, thus suggesting an underlying long-range position effect mechanism. Secondly, cryptic complexity and a chromothripsis rearrangement was identified in a t(6;7;8;12) carrier with intellectual disability. Two translocations and a heterozygous deletion disrupted SOX5; a dominant nervous system development gene previously reported in similar patients. Finally, a direct gene disruption mechanism was proposed in a t(4;9) carrier with dysmorphic facial features and speech delay. In this case, the der(9) breakpoint directly disrupted NFIB, a gene involved in lung maturation and development of the pons with important functions in main speech processes. To conclude, in contrast to familial ABT cases with identical rearrangements and discordant phenotypes, where translocations are considered coincidental, translocations seem to be associated with phenotype presentation in affected de novo ABT cases. In addition, this study highlights the importance of investigating both coding and non-coding regions to decipher the underlying pathogenic mechanisms in these patients, and supports the potential introduction of low coverage WG-MPS in the clinical investigation of de novo ABTs.
Competing Interests: The authors have declared that no competing interests exist.
References: Hum Mol Genet. 1996 Sep;5(9):1229-35. (PMID: 8872461)
Ann Genet. 1983;26(3):133-7. (PMID: 6606374)
Eur J Med Genet. 2009 Sep-Oct;52(5):291-6. (PMID: 19505601)
Am J Hum Genet. 1991 Nov;49(5):995-1013. (PMID: 1928105)
Eur J Hum Genet. 2004 Aug;12(8):647-53. (PMID: 15162125)
J Neurosci. 1999 Jul 15;19(14):5980-9. (PMID: 10407036)
Cell. 2014 Dec 18;159(7):1665-80. (PMID: 25497547)
Am J Hum Genet. 2005 Jan;76(1):8-32. (PMID: 15549674)
PLoS One. 2017 Jan 10;12(1):e0169935. (PMID: 28072833)
Ophthalmic Genet. 2000 Sep;21(3):185-9. (PMID: 11035551)
Neuron. 2008 Jan 24;57(2):232-47. (PMID: 18215621)
Am J Audiol. 2014 Mar;23(1):1-6. (PMID: 24096866)
Genome Res. 2009 Sep;19(9):1639-45. (PMID: 19541911)
Hum Mol Genet. 1998;7(10):1611-8. (PMID: 9735382)
Hum Mutat. 2012 Apr;33(4):728-40. (PMID: 22290657)
Hum Mol Genet. 1995 Nov;4(11):2145-50. (PMID: 8589693)
Neurogenetics. 2015 Oct;16(4):287-98. (PMID: 26163108)
Nature. 2012 Apr 11;485(7398):376-80. (PMID: 22495300)
Nat Neurosci. 2016 Sep;19(9):1194-6. (PMID: 27479843)
J Comp Neurol. 2009 Mar 1;513(1):98-112. (PMID: 19107796)
Chin Med J (Engl). 2017 5th Jan 2017;130(1):88-92. (PMID: 28051029)
Am J Hum Genet. 2018 Jun 7;102(6):1090-1103. (PMID: 29805044)
PLoS Genet. 2010 Oct 14;6(10):e1001154. (PMID: 20976243)
Hum Genet. 2010 Oct;128(4):411-9. (PMID: 20668882)
Clin Genet. 2009 Dec;76(6):558-63. (PMID: 19930154)
J Med Genet. 1993 Sep;30(9):713-27. (PMID: 8411066)
Semin Reprod Med. 2001 Jun;19(2):183-91. (PMID: 11480916)
Neuro Endocrinol Lett. 2006 Oct;27(5):579-85. (PMID: 17159828)
Mol Cytogenet. 2008 Jul 21;1:15. (PMID: 18644119)
Methods Mol Biol. 2000;132:365-86. (PMID: 10547847)
Am J Hum Genet. 1992 Dec;51(6):1229-39. (PMID: 1281384)
Science. 1995 Feb 3;267(5198):685-8. (PMID: 7839145)
Bioinformatics. 2010 Aug 1;26(15):1895-6. (PMID: 20639544)
Arch Otolaryngol Head Neck Surg. 2005 Dec;131(12):1057-63. (PMID: 16365218)
Mol Cell Biol. 2005 Jan;25(2):685-98. (PMID: 15632069)
Development. 2004 Sep;131(18):4455-65. (PMID: 15306568)
Physiology (Bethesda). 2005 Feb;20:60-9. (PMID: 15653841)
Behav Neurosci. 1989 Oct;103(5):998-1008. (PMID: 2679667)
Am J Hum Genet. 2001 Aug;69(2):261-8. (PMID: 11431708)
المشرفين على المادة: 0 (NFI Transcription Factors)
0 (NFIB protein, human)
0 (POU Domain Factors)
0 (POU3F4 protein, human)
0 (SOX5 protein, human)
0 (SOXD Transcription Factors)
تواريخ الأحداث: Date Created: 20181006 Date Completed: 20190320 Latest Revision: 20190320
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC6173455
DOI: 10.1371/journal.pone.0205298
PMID: 30289920
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0205298