Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith–Magenis syndrome with evident peripheral neuropathy

21 páginas

Autores:: Yuan, Bo
Neira, Juanita
Gu, Shen
Harel, Tamar
Liu, Pengfei
Briceño Balcázar, Ignacio
Elsea, Sarah H.
Gómez Gutiérrez, Alberto
Potocki, Lorraine
Lupski, James R.

Tipo de recurso:

Fecha de publicación:: 2017

Institución:: Universidad de la Sabana

Repositorio:: Repositorio Universidad de la Sabana

Idioma:: eng

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spelling	Yuan, BoNeira, JuanitaGu, ShenHarel, TamarLiu, PengfeiBriceño Balcázar, IgnacioElsea, Sarah H.Gómez Gutiérrez, AlbertoPotocki, LorraineLupski, James R.5/21/2018 9:422018-05-21T14:42:02Z2017-10-01Yuan, B. Neira, J. Gu, S, Harel, T. Liu, P. Briceño, I. Elsea, SH. Gómez, A. Potocki, L. Lupski JR (2016). Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith-Magenis syndrome with evident peripheral neuropathy. Human Genetics. 135(10), 1161-1174 doi 10.1007/s00439-016-1703-5 ISSN 03406717, 14321203https://www.ncbi.nlm.nih.gov/pubmed/27386852https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021589/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021589/pdf/nihms801552.pdfhttp://hdl.handle.net/10818/3297010.1007/s00439-016-1703-521 páginasHereditary neuropathy with liability to pressure palsies (HNPP) and Smith-Magenis syndrome (SMS) are genomic disorders associated with deletion copy number variants involving chromosome 17p12 and 17p11.2, respectively. Nonallelic homologous recombination (NAHR)-mediated recurrent deletions are responsible for the majority of HNPP and SMS cases; the rearrangement products encompass the key dosage-sensitive genes PMP22 and RAI1, respectively, and result in haploinsufficiency for these genes. Less frequently, nonrecurrent genomic rearrangements occur at this locus. Contiguous gene duplications encompassing both PMP22 and RAI1, i.e., PMP22-RAI1 duplications, have been investigated, and replication-based mechanisms rather than NAHR have been proposed for these rearrangements. In the current study, we report molecular and clinical characterizations of six subjects with the reciprocal phenomenon of deletions spanning both genes, i.e., PMP22-RAI1 deletions. Molecular studies utilizing high-resolution array comparative genomic hybridization and breakpoint junction sequencing identified mutational signatures that were suggestive of replication-based mechanisms. Systematic clinical studies revealed features consistent with SMS, including features of intellectual disability, speech and gross motor delays, behavioral problems and ocular abnormalities. Five out of six subjects presented clinical signs and/or objective electrophysiologic studies of peripheral neuropathy. Clinical profiling may improve the clinical management of this unique group of subjects, as the peripheral neuropathy can be more severe or of earlier onset as compared to SMS patients having the common recurrent deletion. Moreover, the current study, in combination with the previous report of PMP22-RAI1 duplications, contributes to the understanding of rare complex phenotypes involving multiple dosage-sensitive genes from a genetic mechanistic standpoint.application/pdfengHuman GeneticsHum Genet. 2016 Oct; 135(10): 1161–1174Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/http://purl.org/coar/access_right/c_abf2Universidad de La SabanaIntellectum Repositorio Universidad de La SabanaContiguous gene deletionPMP22RAI1FoSTeS/MMBIRNonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith–Magenis syndrome with evident peripheral neuropathyarticlepublishedVersionhttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-81223https://intellectum.unisabana.edu.co/bitstream/10818/32970/2/license_rdf7c9ab7f006165862d8ce9ac5eac01552MD5210818/32970oai:intellectum.unisabana.edu.co:10818/329702022-05-10 05:17:39.931Intellectum Universidad de la Sabanacontactointellectum@unisabana.edu.co
dc.title.es_CO.fl_str_mv	Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith–Magenis syndrome with evident peripheral neuropathy
title	Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith–Magenis syndrome with evident peripheral neuropathy
spellingShingle	Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith–Magenis syndrome with evident peripheral neuropathy Contiguous gene deletion PMP22 RAI1 FoSTeS/MMBIR
title_short	Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith–Magenis syndrome with evident peripheral neuropathy
title_full	Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith–Magenis syndrome with evident peripheral neuropathy
title_fullStr	Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith–Magenis syndrome with evident peripheral neuropathy
title_full_unstemmed	Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith–Magenis syndrome with evident peripheral neuropathy
title_sort	Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith–Magenis syndrome with evident peripheral neuropathy
dc.creator.fl_str_mv	Yuan, Bo Neira, Juanita Gu, Shen Harel, Tamar Liu, Pengfei Briceño Balcázar, Ignacio Elsea, Sarah H. Gómez Gutiérrez, Alberto Potocki, Lorraine Lupski, James R.
dc.contributor.author.none.fl_str_mv	Yuan, Bo Neira, Juanita Gu, Shen Harel, Tamar Liu, Pengfei Briceño Balcázar, Ignacio Elsea, Sarah H. Gómez Gutiérrez, Alberto Potocki, Lorraine Lupski, James R.
dc.subject.es_CO.fl_str_mv	Contiguous gene deletion PMP22 RAI1 FoSTeS/MMBIR
topic	Contiguous gene deletion PMP22 RAI1 FoSTeS/MMBIR
description	21 páginas
publishDate	2017
dc.date.issued.none.fl_str_mv	2017-10-01
dc.date.available.none.fl_str_mv	2018-05-21T14:42:02Z
dc.date.accessioned.none.fl_str_mv	5/21/2018 9:42
dc.type.en.fl_str_mv	article
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dc.identifier.citation.es_CO.fl_str_mv	Yuan, B. Neira, J. Gu, S, Harel, T. Liu, P. Briceño, I. Elsea, SH. Gómez, A. Potocki, L. Lupski JR (2016). Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith-Magenis syndrome with evident peripheral neuropathy. Human Genetics. 135(10), 1161-1174 doi 10.1007/s00439-016-1703-5 ISSN 03406717, 14321203
dc.identifier.other.none.fl_str_mv	https://www.ncbi.nlm.nih.gov/pubmed/27386852 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021589/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021589/pdf/nihms801552.pdf
dc.identifier.uri.none.fl_str_mv	http://hdl.handle.net/10818/32970
dc.identifier.doi.none.fl_str_mv	10.1007/s00439-016-1703-5
identifier_str_mv	Yuan, B. Neira, J. Gu, S, Harel, T. Liu, P. Briceño, I. Elsea, SH. Gómez, A. Potocki, L. Lupski JR (2016). Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith-Magenis syndrome with evident peripheral neuropathy. Human Genetics. 135(10), 1161-1174 doi 10.1007/s00439-016-1703-5 ISSN 03406717, 14321203 10.1007/s00439-016-1703-5
url	https://www.ncbi.nlm.nih.gov/pubmed/27386852 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021589/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021589/pdf/nihms801552.pdf http://hdl.handle.net/10818/32970
dc.language.iso.es_CO.fl_str_mv	eng
language	eng
dc.relation.ispartofseries.none.fl_str_mv	Hum Genet. 2016 Oct; 135(10): 1161–1174
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dc.publisher.es_CO.fl_str_mv	Human Genetics
dc.source.es_CO.fl_str_mv	Universidad de La Sabana Intellectum Repositorio Universidad de La Sabana
institution	Universidad de la Sabana
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Nonrecurrent PMP22-RAI1 contiguous gene deletions arise from replication-based mechanisms and result in Smith–Magenis syndrome with evident peripheral neuropathy

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