NGS panel analysis in 24 ectopia lentis patients; a clinically relevant test with a high diagnostic yield
Abstract Background Several genetic causes of ectopia lentis (EL), with or without systemic features, are known. The differentiation between syndromic and isolated EL is crucial for further treatment, surveillance and counseling of patients and their relatives. Next generation sequencing (NGS) is a...
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| Veröffentlicht in: | European journal of medical genetics 2017-09, Vol.60 (9), p.465-473 |
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| creator | Overwater, E Floor, K van Beek, D de Boer, K van Dijk, T Hilhorst-Hofstee, Y Hoogeboom, A.J.M van Kaam, K.J van de Kamp, J.M Kempers, M Krapels, I.P.C Kroes, H.Y Loeys, B Salemink, S Stumpel, C.T.R.M Verhoeven, V.J.M Wijnands-van den Berg, E Cobben, J.M van Tintelen, J.P Weiss, M.M Houweling, A.C Maugeri, A |
| description | Abstract Background Several genetic causes of ectopia lentis (EL), with or without systemic features, are known. The differentiation between syndromic and isolated EL is crucial for further treatment, surveillance and counseling of patients and their relatives. Next generation sequencing (NGS) is a powerful tool enabling the simultaneous, highly-sensitive analysis of multiple target genes. Objective The aim of this study was to evaluate the diagnostic yield of our NGS panel in EL patients. Furthermore, we provide an overview of currently described mutations in ADAMTSL4 , the main gene involved in isolated EL. Methods A NGS gene panel was analysed in 24 patients with EL. Results A genetic diagnosis was confirmed in 16 patients (67%). Of these, four (25%) had a heterozygous FBN1 mutation, 12 (75%) were homozygous or compound heterozygous for ADAMTSL4 mutations. The known European ADAMTSL4 founder mutation c.767_786del was most frequently detected. Conclusion The diagnostic yield of our NGS panel was high. Causative mutations were exclusively identified in ADAMTSL4 and FBN1 . With this approach the risk of misdiagnosis or delayed diagnosis can be reduced. The value and clinical implications of establishing a genetic diagnosis in patients with EL is corroborated by the description of two patients with an unexpected underlying genetic condition. |
| doi_str_mv | 10.1016/j.ejmg.2017.06.005 |
| format | Article |
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The differentiation between syndromic and isolated EL is crucial for further treatment, surveillance and counseling of patients and their relatives. Next generation sequencing (NGS) is a powerful tool enabling the simultaneous, highly-sensitive analysis of multiple target genes. Objective The aim of this study was to evaluate the diagnostic yield of our NGS panel in EL patients. Furthermore, we provide an overview of currently described mutations in ADAMTSL4 , the main gene involved in isolated EL. Methods A NGS gene panel was analysed in 24 patients with EL. Results A genetic diagnosis was confirmed in 16 patients (67%). Of these, four (25%) had a heterozygous FBN1 mutation, 12 (75%) were homozygous or compound heterozygous for ADAMTSL4 mutations. The known European ADAMTSL4 founder mutation c.767_786del was most frequently detected. Conclusion The diagnostic yield of our NGS panel was high. Causative mutations were exclusively identified in ADAMTSL4 and FBN1 . With this approach the risk of misdiagnosis or delayed diagnosis can be reduced. The value and clinical implications of establishing a genetic diagnosis in patients with EL is corroborated by the description of two patients with an unexpected underlying genetic condition.</description><identifier>ISSN: 1769-7212</identifier><identifier>EISSN: 1878-0849</identifier><identifier>DOI: 10.1016/j.ejmg.2017.06.005</identifier><identifier>PMID: 28642162</identifier><language>eng</language><publisher>Netherlands: Elsevier Masson SAS</publisher><subject>ADAMTS Proteins - genetics ; ADAMTSL4 ; Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Ectopia lentis ; Ectopia Lentis - diagnosis ; Ectopia Lentis - genetics ; False Positive Reactions ; FBN1 ; Female ; Gene panel ; Genetic Testing - methods ; Genetic Testing - standards ; High-Throughput Nucleotide Sequencing - methods ; High-Throughput Nucleotide Sequencing - standards ; Humans ; Infant ; Male ; Medical Education ; Middle Aged ; Next generation sequencing ; Sensitivity and Specificity ; Sequence Analysis, DNA - methods ; Sequence Analysis, DNA - standards</subject><ispartof>European journal of medical genetics, 2017-09, Vol.60 (9), p.465-473</ispartof><rights>2017 Elsevier Masson SAS</rights><rights>Copyright © 2017 Elsevier Masson SAS. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c411t-af574af0d3b701fc93a00729184575e75bda7fa8364242106a41461a00d3f1903</citedby><cites>FETCH-LOGICAL-c411t-af574af0d3b701fc93a00729184575e75bda7fa8364242106a41461a00d3f1903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1769721216302117$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28642162$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Overwater, E</creatorcontrib><creatorcontrib>Floor, K</creatorcontrib><creatorcontrib>van Beek, D</creatorcontrib><creatorcontrib>de Boer, K</creatorcontrib><creatorcontrib>van Dijk, T</creatorcontrib><creatorcontrib>Hilhorst-Hofstee, Y</creatorcontrib><creatorcontrib>Hoogeboom, A.J.M</creatorcontrib><creatorcontrib>van Kaam, K.J</creatorcontrib><creatorcontrib>van de Kamp, J.M</creatorcontrib><creatorcontrib>Kempers, M</creatorcontrib><creatorcontrib>Krapels, I.P.C</creatorcontrib><creatorcontrib>Kroes, H.Y</creatorcontrib><creatorcontrib>Loeys, B</creatorcontrib><creatorcontrib>Salemink, S</creatorcontrib><creatorcontrib>Stumpel, C.T.R.M</creatorcontrib><creatorcontrib>Verhoeven, V.J.M</creatorcontrib><creatorcontrib>Wijnands-van den Berg, E</creatorcontrib><creatorcontrib>Cobben, J.M</creatorcontrib><creatorcontrib>van Tintelen, J.P</creatorcontrib><creatorcontrib>Weiss, M.M</creatorcontrib><creatorcontrib>Houweling, A.C</creatorcontrib><creatorcontrib>Maugeri, A</creatorcontrib><title>NGS panel analysis in 24 ectopia lentis patients; a clinically relevant test with a high diagnostic yield</title><title>European journal of medical genetics</title><addtitle>Eur J Med Genet</addtitle><description>Abstract Background Several genetic causes of ectopia lentis (EL), with or without systemic features, are known. The differentiation between syndromic and isolated EL is crucial for further treatment, surveillance and counseling of patients and their relatives. Next generation sequencing (NGS) is a powerful tool enabling the simultaneous, highly-sensitive analysis of multiple target genes. Objective The aim of this study was to evaluate the diagnostic yield of our NGS panel in EL patients. Furthermore, we provide an overview of currently described mutations in ADAMTSL4 , the main gene involved in isolated EL. Methods A NGS gene panel was analysed in 24 patients with EL. Results A genetic diagnosis was confirmed in 16 patients (67%). Of these, four (25%) had a heterozygous FBN1 mutation, 12 (75%) were homozygous or compound heterozygous for ADAMTSL4 mutations. The known European ADAMTSL4 founder mutation c.767_786del was most frequently detected. Conclusion The diagnostic yield of our NGS panel was high. Causative mutations were exclusively identified in ADAMTSL4 and FBN1 . With this approach the risk of misdiagnosis or delayed diagnosis can be reduced. The value and clinical implications of establishing a genetic diagnosis in patients with EL is corroborated by the description of two patients with an unexpected underlying genetic condition.</description><subject>ADAMTS Proteins - genetics</subject><subject>ADAMTSL4</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Ectopia lentis</subject><subject>Ectopia Lentis - diagnosis</subject><subject>Ectopia Lentis - genetics</subject><subject>False Positive Reactions</subject><subject>FBN1</subject><subject>Female</subject><subject>Gene panel</subject><subject>Genetic Testing - methods</subject><subject>Genetic Testing - standards</subject><subject>High-Throughput Nucleotide Sequencing - methods</subject><subject>High-Throughput Nucleotide Sequencing - standards</subject><subject>Humans</subject><subject>Infant</subject><subject>Male</subject><subject>Medical Education</subject><subject>Middle Aged</subject><subject>Next generation sequencing</subject><subject>Sensitivity and Specificity</subject><subject>Sequence Analysis, DNA - methods</subject><subject>Sequence Analysis, DNA - standards</subject><issn>1769-7212</issn><issn>1878-0849</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9v1DAQxS0Eon_gC3BAPnJJmLGTOBEICVW0RaraQ-FseR1n18GbhNhblG_fibblwIGTR_Z7I7_fY-wdQo6A1cc-d_1-mwtAlUOVA5Qv2CnWqs6gLpqXNKuqyZRAccLOYuwBZI2iec1ORF0VAitxyvzt1T2fzOACN4MJS_SR-4GLgjubxskbHtyQ6HIyydMUP3HDbfCDtyaEhc8uuAczJJ5cTPyPTzt63_ntjrfebIcxJm_54l1o37BXnQnRvX06z9nPy28_Lq6zm7ur7xdfbzJbIKbMdKUqTAet3CjAzjbSACjRYF2UqnSq3LRGdaaWlIAyQGUKLCokUSs7bECesw_HvdM8_j7Qr_TeR-tCoJDjIWpsUMpGkJKk4ii18xjj7Do9zX5v5kUj6BWx7vWKWK-INVSaEJPp_dP-w2bv2r-WZ6Yk-HwUOEr54N2soyV01rV-Jqi6Hf3_93_5x_6M-5dbXOzHw0xFUQ4dhQZ9v5a8doyVBIGo5CNhU6Cx</recordid><startdate>20170901</startdate><enddate>20170901</enddate><creator>Overwater, E</creator><creator>Floor, K</creator><creator>van Beek, D</creator><creator>de Boer, K</creator><creator>van Dijk, T</creator><creator>Hilhorst-Hofstee, Y</creator><creator>Hoogeboom, A.J.M</creator><creator>van Kaam, K.J</creator><creator>van de Kamp, J.M</creator><creator>Kempers, M</creator><creator>Krapels, I.P.C</creator><creator>Kroes, H.Y</creator><creator>Loeys, B</creator><creator>Salemink, S</creator><creator>Stumpel, C.T.R.M</creator><creator>Verhoeven, V.J.M</creator><creator>Wijnands-van den Berg, E</creator><creator>Cobben, J.M</creator><creator>van Tintelen, J.P</creator><creator>Weiss, M.M</creator><creator>Houweling, A.C</creator><creator>Maugeri, A</creator><general>Elsevier Masson SAS</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20170901</creationdate><title>NGS panel analysis in 24 ectopia lentis patients; a clinically relevant test with a high diagnostic yield</title><author>Overwater, E ; Floor, K ; van Beek, D ; de Boer, K ; van Dijk, T ; Hilhorst-Hofstee, Y ; Hoogeboom, A.J.M ; van Kaam, K.J ; van de Kamp, J.M ; Kempers, M ; Krapels, I.P.C ; Kroes, H.Y ; Loeys, B ; Salemink, S ; Stumpel, C.T.R.M ; Verhoeven, V.J.M ; Wijnands-van den Berg, E ; Cobben, J.M ; van Tintelen, J.P ; Weiss, M.M ; Houweling, A.C ; Maugeri, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c411t-af574af0d3b701fc93a00729184575e75bda7fa8364242106a41461a00d3f1903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>ADAMTS Proteins - genetics</topic><topic>ADAMTSL4</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Ectopia lentis</topic><topic>Ectopia Lentis - diagnosis</topic><topic>Ectopia Lentis - genetics</topic><topic>False Positive Reactions</topic><topic>FBN1</topic><topic>Female</topic><topic>Gene panel</topic><topic>Genetic Testing - methods</topic><topic>Genetic Testing - standards</topic><topic>High-Throughput Nucleotide Sequencing - methods</topic><topic>High-Throughput Nucleotide Sequencing - standards</topic><topic>Humans</topic><topic>Infant</topic><topic>Male</topic><topic>Medical Education</topic><topic>Middle Aged</topic><topic>Next generation sequencing</topic><topic>Sensitivity and Specificity</topic><topic>Sequence Analysis, DNA - methods</topic><topic>Sequence Analysis, DNA - standards</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Overwater, E</creatorcontrib><creatorcontrib>Floor, K</creatorcontrib><creatorcontrib>van Beek, D</creatorcontrib><creatorcontrib>de Boer, K</creatorcontrib><creatorcontrib>van Dijk, T</creatorcontrib><creatorcontrib>Hilhorst-Hofstee, Y</creatorcontrib><creatorcontrib>Hoogeboom, A.J.M</creatorcontrib><creatorcontrib>van Kaam, K.J</creatorcontrib><creatorcontrib>van de Kamp, J.M</creatorcontrib><creatorcontrib>Kempers, M</creatorcontrib><creatorcontrib>Krapels, I.P.C</creatorcontrib><creatorcontrib>Kroes, H.Y</creatorcontrib><creatorcontrib>Loeys, B</creatorcontrib><creatorcontrib>Salemink, S</creatorcontrib><creatorcontrib>Stumpel, C.T.R.M</creatorcontrib><creatorcontrib>Verhoeven, V.J.M</creatorcontrib><creatorcontrib>Wijnands-van den Berg, E</creatorcontrib><creatorcontrib>Cobben, J.M</creatorcontrib><creatorcontrib>van Tintelen, J.P</creatorcontrib><creatorcontrib>Weiss, M.M</creatorcontrib><creatorcontrib>Houweling, A.C</creatorcontrib><creatorcontrib>Maugeri, A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of medical genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Overwater, E</au><au>Floor, K</au><au>van Beek, D</au><au>de Boer, K</au><au>van Dijk, T</au><au>Hilhorst-Hofstee, Y</au><au>Hoogeboom, A.J.M</au><au>van Kaam, K.J</au><au>van de Kamp, J.M</au><au>Kempers, M</au><au>Krapels, I.P.C</au><au>Kroes, H.Y</au><au>Loeys, B</au><au>Salemink, S</au><au>Stumpel, C.T.R.M</au><au>Verhoeven, V.J.M</au><au>Wijnands-van den Berg, E</au><au>Cobben, J.M</au><au>van Tintelen, J.P</au><au>Weiss, M.M</au><au>Houweling, A.C</au><au>Maugeri, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NGS panel analysis in 24 ectopia lentis patients; a clinically relevant test with a high diagnostic yield</atitle><jtitle>European journal of medical genetics</jtitle><addtitle>Eur J Med Genet</addtitle><date>2017-09-01</date><risdate>2017</risdate><volume>60</volume><issue>9</issue><spage>465</spage><epage>473</epage><pages>465-473</pages><issn>1769-7212</issn><eissn>1878-0849</eissn><abstract>Abstract Background Several genetic causes of ectopia lentis (EL), with or without systemic features, are known. The differentiation between syndromic and isolated EL is crucial for further treatment, surveillance and counseling of patients and their relatives. Next generation sequencing (NGS) is a powerful tool enabling the simultaneous, highly-sensitive analysis of multiple target genes. Objective The aim of this study was to evaluate the diagnostic yield of our NGS panel in EL patients. Furthermore, we provide an overview of currently described mutations in ADAMTSL4 , the main gene involved in isolated EL. Methods A NGS gene panel was analysed in 24 patients with EL. Results A genetic diagnosis was confirmed in 16 patients (67%). Of these, four (25%) had a heterozygous FBN1 mutation, 12 (75%) were homozygous or compound heterozygous for ADAMTSL4 mutations. The known European ADAMTSL4 founder mutation c.767_786del was most frequently detected. Conclusion The diagnostic yield of our NGS panel was high. Causative mutations were exclusively identified in ADAMTSL4 and FBN1 . With this approach the risk of misdiagnosis or delayed diagnosis can be reduced. The value and clinical implications of establishing a genetic diagnosis in patients with EL is corroborated by the description of two patients with an unexpected underlying genetic condition.</abstract><cop>Netherlands</cop><pub>Elsevier Masson SAS</pub><pmid>28642162</pmid><doi>10.1016/j.ejmg.2017.06.005</doi><tpages>9</tpages></addata></record> |
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| ispartof | European journal of medical genetics, 2017-09, Vol.60 (9), p.465-473 |
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| subjects | ADAMTS Proteins - genetics ADAMTSL4 Adolescent Adult Aged Child Child, Preschool Ectopia lentis Ectopia Lentis - diagnosis Ectopia Lentis - genetics False Positive Reactions FBN1 Female Gene panel Genetic Testing - methods Genetic Testing - standards High-Throughput Nucleotide Sequencing - methods High-Throughput Nucleotide Sequencing - standards Humans Infant Male Medical Education Middle Aged Next generation sequencing Sensitivity and Specificity Sequence Analysis, DNA - methods Sequence Analysis, DNA - standards |
| title | NGS panel analysis in 24 ectopia lentis patients; a clinically relevant test with a high diagnostic yield |
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