Pronounced maternal parent-of-origin bias for type-1 NF1 microdeletions
Neurofibromatosis type 1 (NF1) is caused, in 4.7–11% of cases, by large deletions encompassing the NF1 gene and its flanking regions within 17q11.2. Different types of large NF1 deletion occur which are distinguishable by their breakpoint location and underlying mutational mechanism. Most common are...
Gespeichert in:
| Veröffentlicht in: | Human genetics 2018-05, Vol.137 (5), p.365-373 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 373 |
|---|---|
| container_issue | 5 |
| container_start_page | 365 |
| container_title | Human genetics |
| container_volume | 137 |
| creator | Neuhäusler, Lisa Summerer, Anna Cooper, David N. Mautner, Victor-F. Kehrer-Sawatzki, Hildegard |
| description | Neurofibromatosis type 1 (NF1) is caused, in 4.7–11% of cases, by large deletions encompassing the
NF1
gene and its flanking regions within 17q11.2. Different types of large
NF1
deletion occur which are distinguishable by their breakpoint location and underlying mutational mechanism. Most common are the type-1
NF1
deletions of 1.4 Mb which exhibit recurrent breakpoints caused by nonallelic homologous recombination (NAHR), also termed unequal crossover. Here, we analyzed 37 unrelated families of patients with de novo type-1
NF1
deletions by means of short tandem repeat (STR) profiling to determine the parental origin of the deletions. We observed that 33 of the 37 type-1 deletions were of maternal origin (89.2% of cases;
p
|
| doi_str_mv | 10.1007/s00439-018-1888-x |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2035705949</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A540830939</galeid><sourcerecordid>A540830939</sourcerecordid><originalsourceid>FETCH-LOGICAL-c516t-a98272e3c69ada51a8eeb2d71b518cb16c544b77dc9fc7c430625a51944dbb723</originalsourceid><addsrcrecordid>eNp1kc1rFTEUxYMo9ln9A9zIgBtdpObmYzJZlmJroaj4sQ6ZzJ3HlJnkmczA639vxlctT5S7CNz8zoFzDyEvgZ0BY_pdZkwKQxk0FJqmoftHZANScAqcicdkw4RktNagT8iznG8ZA2W4ekpOuNGCaYANufqcYohL8NhVk5sxBTdWO5cwzDT2NKZhO4SqHVyu-piq-W6HFKqPl1BNg0-xwxHnIYb8nDzp3Zjxxf17Sr5fvv928YHefLq6vji_oV5BPVNnGq45Cl8b1zkFrkFseaehVdD4FmqvpGy17rzpvfZSsJqrwhkpu7bVXJySNwffXYo_FsyznYbscRxdwLhkW4IrzZSRpqCv_0Jv47Lm-0XJRnMp2QO1dSPaIfRxTs6vpvZcSdYIZsTqdfYPqkyH5Q4xYD-U_ZHg7ZGgMDPu561bcrbXX78cs3Bgy0FzTtjbXRoml-4sMLsWbQ9F21K0XYu2-6J5dR9uaSfs_ih-N1sAfgBy-QpbTA_p_-_6E3Xvr8A</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2034872440</pqid></control><display><type>article</type><title>Pronounced maternal parent-of-origin bias for type-1 NF1 microdeletions</title><source>SpringerLink Journals - AutoHoldings</source><creator>Neuhäusler, Lisa ; Summerer, Anna ; Cooper, David N. ; Mautner, Victor-F. ; Kehrer-Sawatzki, Hildegard</creator><creatorcontrib>Neuhäusler, Lisa ; Summerer, Anna ; Cooper, David N. ; Mautner, Victor-F. ; Kehrer-Sawatzki, Hildegard</creatorcontrib><description>Neurofibromatosis type 1 (NF1) is caused, in 4.7–11% of cases, by large deletions encompassing the
NF1
gene and its flanking regions within 17q11.2. Different types of large
NF1
deletion occur which are distinguishable by their breakpoint location and underlying mutational mechanism. Most common are the type-1
NF1
deletions of 1.4 Mb which exhibit recurrent breakpoints caused by nonallelic homologous recombination (NAHR), also termed unequal crossover. Here, we analyzed 37 unrelated families of patients with de novo type-1
NF1
deletions by means of short tandem repeat (STR) profiling to determine the parental origin of the deletions. We observed that 33 of the 37 type-1 deletions were of maternal origin (89.2% of cases;
p
< 0.0001). Analysis of the patients’ siblings indicated that, in 14 informative cases, ten (71.4%) deletions resulted from interchromosomal unequal crossover during meiosis I. Our findings indicate a strong maternal parent-of-origin bias for type-1
NF1
deletions. A similarly pronounced maternal transmission bias has been reported for recurrent copy number variants (CNVs) within 16p11.2 associated with autism, but not so far for any other NAHR-mediated pathogenic CNVs. Region-specific genomic features are likely to be responsible for the maternal bias in the origin of both the 16p11.2 CNVs and type-1
NF1
deletions.</description><identifier>ISSN: 0340-6717</identifier><identifier>EISSN: 1432-1203</identifier><identifier>DOI: 10.1007/s00439-018-1888-x</identifier><identifier>PMID: 29730711</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Autism ; Bias ; Biomedical and Life Sciences ; Biomedicine ; Breakpoints ; Copy number ; Gene Function ; Genetic disorders ; Homologous recombination ; Human Genetics ; Meiosis ; Metabolic Diseases ; Molecular Medicine ; Neurofibromatosis ; Neurofibromin 1 ; Neurological disorders ; Original Investigation ; Recklinghausen's disease ; Tumors</subject><ispartof>Human genetics, 2018-05, Vol.137 (5), p.365-373</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2018</rights><rights>COPYRIGHT 2018 Springer</rights><rights>Human Genetics is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c516t-a98272e3c69ada51a8eeb2d71b518cb16c544b77dc9fc7c430625a51944dbb723</citedby><cites>FETCH-LOGICAL-c516t-a98272e3c69ada51a8eeb2d71b518cb16c544b77dc9fc7c430625a51944dbb723</cites><orcidid>0000-0002-3398-5913</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00439-018-1888-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00439-018-1888-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29730711$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Neuhäusler, Lisa</creatorcontrib><creatorcontrib>Summerer, Anna</creatorcontrib><creatorcontrib>Cooper, David N.</creatorcontrib><creatorcontrib>Mautner, Victor-F.</creatorcontrib><creatorcontrib>Kehrer-Sawatzki, Hildegard</creatorcontrib><title>Pronounced maternal parent-of-origin bias for type-1 NF1 microdeletions</title><title>Human genetics</title><addtitle>Hum Genet</addtitle><addtitle>Hum Genet</addtitle><description>Neurofibromatosis type 1 (NF1) is caused, in 4.7–11% of cases, by large deletions encompassing the
NF1
gene and its flanking regions within 17q11.2. Different types of large
NF1
deletion occur which are distinguishable by their breakpoint location and underlying mutational mechanism. Most common are the type-1
NF1
deletions of 1.4 Mb which exhibit recurrent breakpoints caused by nonallelic homologous recombination (NAHR), also termed unequal crossover. Here, we analyzed 37 unrelated families of patients with de novo type-1
NF1
deletions by means of short tandem repeat (STR) profiling to determine the parental origin of the deletions. We observed that 33 of the 37 type-1 deletions were of maternal origin (89.2% of cases;
p
< 0.0001). Analysis of the patients’ siblings indicated that, in 14 informative cases, ten (71.4%) deletions resulted from interchromosomal unequal crossover during meiosis I. Our findings indicate a strong maternal parent-of-origin bias for type-1
NF1
deletions. A similarly pronounced maternal transmission bias has been reported for recurrent copy number variants (CNVs) within 16p11.2 associated with autism, but not so far for any other NAHR-mediated pathogenic CNVs. Region-specific genomic features are likely to be responsible for the maternal bias in the origin of both the 16p11.2 CNVs and type-1
NF1
deletions.</description><subject>Autism</subject><subject>Bias</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Breakpoints</subject><subject>Copy number</subject><subject>Gene Function</subject><subject>Genetic disorders</subject><subject>Homologous recombination</subject><subject>Human Genetics</subject><subject>Meiosis</subject><subject>Metabolic Diseases</subject><subject>Molecular Medicine</subject><subject>Neurofibromatosis</subject><subject>Neurofibromin 1</subject><subject>Neurological disorders</subject><subject>Original Investigation</subject><subject>Recklinghausen's disease</subject><subject>Tumors</subject><issn>0340-6717</issn><issn>1432-1203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kc1rFTEUxYMo9ln9A9zIgBtdpObmYzJZlmJroaj4sQ6ZzJ3HlJnkmczA639vxlctT5S7CNz8zoFzDyEvgZ0BY_pdZkwKQxk0FJqmoftHZANScAqcicdkw4RktNagT8iznG8ZA2W4ekpOuNGCaYANufqcYohL8NhVk5sxBTdWO5cwzDT2NKZhO4SqHVyu-piq-W6HFKqPl1BNg0-xwxHnIYb8nDzp3Zjxxf17Sr5fvv928YHefLq6vji_oV5BPVNnGq45Cl8b1zkFrkFseaehVdD4FmqvpGy17rzpvfZSsJqrwhkpu7bVXJySNwffXYo_FsyznYbscRxdwLhkW4IrzZSRpqCv_0Jv47Lm-0XJRnMp2QO1dSPaIfRxTs6vpvZcSdYIZsTqdfYPqkyH5Q4xYD-U_ZHg7ZGgMDPu561bcrbXX78cs3Bgy0FzTtjbXRoml-4sMLsWbQ9F21K0XYu2-6J5dR9uaSfs_ih-N1sAfgBy-QpbTA_p_-_6E3Xvr8A</recordid><startdate>20180501</startdate><enddate>20180501</enddate><creator>Neuhäusler, Lisa</creator><creator>Summerer, Anna</creator><creator>Cooper, David N.</creator><creator>Mautner, Victor-F.</creator><creator>Kehrer-Sawatzki, Hildegard</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3398-5913</orcidid></search><sort><creationdate>20180501</creationdate><title>Pronounced maternal parent-of-origin bias for type-1 NF1 microdeletions</title><author>Neuhäusler, Lisa ; Summerer, Anna ; Cooper, David N. ; Mautner, Victor-F. ; Kehrer-Sawatzki, Hildegard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c516t-a98272e3c69ada51a8eeb2d71b518cb16c544b77dc9fc7c430625a51944dbb723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Autism</topic><topic>Bias</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Breakpoints</topic><topic>Copy number</topic><topic>Gene Function</topic><topic>Genetic disorders</topic><topic>Homologous recombination</topic><topic>Human Genetics</topic><topic>Meiosis</topic><topic>Metabolic Diseases</topic><topic>Molecular Medicine</topic><topic>Neurofibromatosis</topic><topic>Neurofibromin 1</topic><topic>Neurological disorders</topic><topic>Original Investigation</topic><topic>Recklinghausen's disease</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Neuhäusler, Lisa</creatorcontrib><creatorcontrib>Summerer, Anna</creatorcontrib><creatorcontrib>Cooper, David N.</creatorcontrib><creatorcontrib>Mautner, Victor-F.</creatorcontrib><creatorcontrib>Kehrer-Sawatzki, Hildegard</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Neuhäusler, Lisa</au><au>Summerer, Anna</au><au>Cooper, David N.</au><au>Mautner, Victor-F.</au><au>Kehrer-Sawatzki, Hildegard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pronounced maternal parent-of-origin bias for type-1 NF1 microdeletions</atitle><jtitle>Human genetics</jtitle><stitle>Hum Genet</stitle><addtitle>Hum Genet</addtitle><date>2018-05-01</date><risdate>2018</risdate><volume>137</volume><issue>5</issue><spage>365</spage><epage>373</epage><pages>365-373</pages><issn>0340-6717</issn><eissn>1432-1203</eissn><abstract>Neurofibromatosis type 1 (NF1) is caused, in 4.7–11% of cases, by large deletions encompassing the
NF1
gene and its flanking regions within 17q11.2. Different types of large
NF1
deletion occur which are distinguishable by their breakpoint location and underlying mutational mechanism. Most common are the type-1
NF1
deletions of 1.4 Mb which exhibit recurrent breakpoints caused by nonallelic homologous recombination (NAHR), also termed unequal crossover. Here, we analyzed 37 unrelated families of patients with de novo type-1
NF1
deletions by means of short tandem repeat (STR) profiling to determine the parental origin of the deletions. We observed that 33 of the 37 type-1 deletions were of maternal origin (89.2% of cases;
p
< 0.0001). Analysis of the patients’ siblings indicated that, in 14 informative cases, ten (71.4%) deletions resulted from interchromosomal unequal crossover during meiosis I. Our findings indicate a strong maternal parent-of-origin bias for type-1
NF1
deletions. A similarly pronounced maternal transmission bias has been reported for recurrent copy number variants (CNVs) within 16p11.2 associated with autism, but not so far for any other NAHR-mediated pathogenic CNVs. Region-specific genomic features are likely to be responsible for the maternal bias in the origin of both the 16p11.2 CNVs and type-1
NF1
deletions.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>29730711</pmid><doi>10.1007/s00439-018-1888-x</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-3398-5913</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0340-6717 |
| ispartof | Human genetics, 2018-05, Vol.137 (5), p.365-373 |
| issn | 0340-6717 1432-1203 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2035705949 |
| source | SpringerLink Journals - AutoHoldings |
| subjects | Autism Bias Biomedical and Life Sciences Biomedicine Breakpoints Copy number Gene Function Genetic disorders Homologous recombination Human Genetics Meiosis Metabolic Diseases Molecular Medicine Neurofibromatosis Neurofibromin 1 Neurological disorders Original Investigation Recklinghausen's disease Tumors |
| title | Pronounced maternal parent-of-origin bias for type-1 NF1 microdeletions |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T17%3A54%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pronounced%20maternal%20parent-of-origin%20bias%20for%20type-1%20NF1%20microdeletions&rft.jtitle=Human%20genetics&rft.au=Neuh%C3%A4usler,%20Lisa&rft.date=2018-05-01&rft.volume=137&rft.issue=5&rft.spage=365&rft.epage=373&rft.pages=365-373&rft.issn=0340-6717&rft.eissn=1432-1203&rft_id=info:doi/10.1007/s00439-018-1888-x&rft_dat=%3Cgale_proqu%3EA540830939%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2034872440&rft_id=info:pmid/29730711&rft_galeid=A540830939&rfr_iscdi=true |