Clinical utility of genetic testing in 201 preschool children with inherited eye disorders

Eva Lenassi; Jill Clayton-Smith; Sofia Douzgou; Simon C Ramsden; Stuart Ingram; Georgina Hall; Claire L Hardcastle; Tracy A Fletcher; Rachel L Taylor; Jamie M Ellingford; William D Newman; Cecilia Fenerty; Vinod Sharma; I Chris Lloyd; Susmito Biswas; Jane L Ashworth; Graeme C Black; Panagiotis I Sergouniotis

doi:10.1038/s41436-019-0722-8

Clinical utility of genetic testing in 201 preschool children with inherited eye disorders

Eva Lenassi, Jill Clayton-Smith, Sofia Douzgou, Simon C Ramsden, Stuart Ingram, Georgina Hall, Claire L Hardcastle, Tracy A Fletcher, Rachel L Taylor, Jamie M Ellingford, William D Newman, Cecilia Fenerty, Vinod Sharma, I Chris Lloyd, Susmito Biswas, Jane L Ashworth, Graeme C Black, Panagiotis I Sergouniotis

Research output: Contribution to journal › Article › peer-review

Abstract

PURPOSE: A key property to consider in all genetic tests is clinical utility, the ability of the test to influence patient management and health outcomes. Here we assess the current clinical utility of genetic testing in diverse pediatric inherited eye disorders (IEDs).

METHODS: Two hundred one unrelated children (0-5 years old) with IEDs were ascertained through the database of the North West Genomic Laboratory Hub, Manchester, UK. The cohort was collected over a 7-year period (2011-2018) and included 74 children with bilateral cataracts, 8 with bilateral ectopia lentis, 28 with bilateral anterior segment dysgenesis, 32 with albinism, and 59 with inherited retinal disorders. All participants underwent panel-based genetic testing.

RESULTS: The diagnostic yield of genetic testing for the cohort was 64% (ranging from 39% to 91% depending on the condition). The test result led to altered management (including preventing additional investigations or resulting in the introduction of personalized surveillance measures) in 33% of probands (75% for ectopia lentis, 50% for cataracts, 33% for inherited retinal disorders, 7% for anterior segment dysgenesis, 3% for albinism).

CONCLUSION: Genetic testing helped identify an etiological diagnosis in the majority of preschool children with IEDs. This prevented additional unnecessary testing and provided the opportunity for anticipatory guidance in significant subsets of patients.

Original language	English
Pages (from-to)	745-751
Number of pages	7
Journal	Genetics in Medicine
Volume	22
Issue number	4
DOIs	https://doi.org/10.1038/s41436-019-0722-8
Publication status	Published - 1 Apr 2020

Keywords

Cataract/diagnosis
Child, Preschool
Eye
Eye Abnormalities/genetics
Genetic Testing
Humans
Infant
Infant, Newborn
Retinal Diseases/diagnosis

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10.1038/s41436-019-0722-8

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Lenassi, E., Clayton-Smith, J., Douzgou, S., Ramsden, S. C., Ingram, S., Hall, G., Hardcastle, C. L., Fletcher, T. A., Taylor, R. L., Ellingford, J. M., Newman, W. D., Fenerty, C., Sharma, V., Lloyd, I. C., Biswas, S., Ashworth, J. L., Black, G. C., & Sergouniotis, P. I. (2020). Clinical utility of genetic testing in 201 preschool children with inherited eye disorders. Genetics in Medicine, 22(4), 745-751. https://doi.org/10.1038/s41436-019-0722-8

@article{1cebc4447cc9401c8f72241d105d4f55,

title = "Clinical utility of genetic testing in 201 preschool children with inherited eye disorders",

abstract = "PURPOSE: A key property to consider in all genetic tests is clinical utility, the ability of the test to influence patient management and health outcomes. Here we assess the current clinical utility of genetic testing in diverse pediatric inherited eye disorders (IEDs).METHODS: Two hundred one unrelated children (0-5 years old) with IEDs were ascertained through the database of the North West Genomic Laboratory Hub, Manchester, UK. The cohort was collected over a 7-year period (2011-2018) and included 74 children with bilateral cataracts, 8 with bilateral ectopia lentis, 28 with bilateral anterior segment dysgenesis, 32 with albinism, and 59 with inherited retinal disorders. All participants underwent panel-based genetic testing.RESULTS: The diagnostic yield of genetic testing for the cohort was 64% (ranging from 39% to 91% depending on the condition). The test result led to altered management (including preventing additional investigations or resulting in the introduction of personalized surveillance measures) in 33% of probands (75% for ectopia lentis, 50% for cataracts, 33% for inherited retinal disorders, 7% for anterior segment dysgenesis, 3% for albinism).CONCLUSION: Genetic testing helped identify an etiological diagnosis in the majority of preschool children with IEDs. This prevented additional unnecessary testing and provided the opportunity for anticipatory guidance in significant subsets of patients.",

keywords = "Cataract/diagnosis, Child, Preschool, Eye, Eye Abnormalities/genetics, Genetic Testing, Humans, Infant, Infant, Newborn, Retinal Diseases/diagnosis",

author = "Eva Lenassi and Jill Clayton-Smith and Sofia Douzgou and Ramsden, {Simon C} and Stuart Ingram and Georgina Hall and Hardcastle, {Claire L} and Fletcher, {Tracy A} and Taylor, {Rachel L} and Ellingford, {Jamie M} and Newman, {William D} and Cecilia Fenerty and Vinod Sharma and Lloyd, {I Chris} and Susmito Biswas and Ashworth, {Jane L} and Black, {Graeme C} and Sergouniotis, {Panagiotis I}",

note = "Funding Information: We acknowledge the following sources of funding: the Wellcome Trust (200990/Z/16/Z, Transforming Genetic Medicine Initiative), Retina UK and Fight for Sight (GR586, RP Genome Project), the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre, and the NIHR Clinical Lecturer Programme (CL-2017-06-001, PIS). This study was supported by the ERN-EYE project (which is cofunded by the Health Program of the European Union under the Framework Partnership Agreement 739534) and by the ERN-ITHACA project (Framework Partnership Agreement 739516). Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2020",

month = apr,

day = "1",

doi = "10.1038/s41436-019-0722-8",

language = "English",

volume = "22",

pages = "745--751",

journal = "Genetics in Medicine",

issn = "1098-3600",

publisher = "Elsevier BV",

number = "4",

}

Lenassi, E, Clayton-Smith, J, Douzgou, S, Ramsden, SC, Ingram, S, Hall, G, Hardcastle, CL, Fletcher, TA, Taylor, RL, Ellingford, JM, Newman, WD, Fenerty, C, Sharma, V, Lloyd, IC, Biswas, S, Ashworth, JL, Black, GC & Sergouniotis, PI 2020, 'Clinical utility of genetic testing in 201 preschool children with inherited eye disorders', Genetics in Medicine, vol. 22, no. 4, pp. 745-751. https://doi.org/10.1038/s41436-019-0722-8

TY - JOUR

T1 - Clinical utility of genetic testing in 201 preschool children with inherited eye disorders

AU - Lenassi, Eva

AU - Clayton-Smith, Jill

AU - Douzgou, Sofia

AU - Ramsden, Simon C

AU - Ingram, Stuart

AU - Hall, Georgina

AU - Hardcastle, Claire L

AU - Fletcher, Tracy A

AU - Taylor, Rachel L

AU - Ellingford, Jamie M

AU - Newman, William D

AU - Fenerty, Cecilia

AU - Sharma, Vinod

AU - Lloyd, I Chris

AU - Biswas, Susmito

AU - Ashworth, Jane L

AU - Black, Graeme C

AU - Sergouniotis, Panagiotis I

N1 - Funding Information: We acknowledge the following sources of funding: the Wellcome Trust (200990/Z/16/Z, Transforming Genetic Medicine Initiative), Retina UK and Fight for Sight (GR586, RP Genome Project), the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre, and the NIHR Clinical Lecturer Programme (CL-2017-06-001, PIS). This study was supported by the ERN-EYE project (which is cofunded by the Health Program of the European Union under the Framework Partnership Agreement 739534) and by the ERN-ITHACA project (Framework Partnership Agreement 739516). Publisher Copyright: © 2019, The Author(s).

PY - 2020/4/1

Y1 - 2020/4/1

N2 - PURPOSE: A key property to consider in all genetic tests is clinical utility, the ability of the test to influence patient management and health outcomes. Here we assess the current clinical utility of genetic testing in diverse pediatric inherited eye disorders (IEDs).METHODS: Two hundred one unrelated children (0-5 years old) with IEDs were ascertained through the database of the North West Genomic Laboratory Hub, Manchester, UK. The cohort was collected over a 7-year period (2011-2018) and included 74 children with bilateral cataracts, 8 with bilateral ectopia lentis, 28 with bilateral anterior segment dysgenesis, 32 with albinism, and 59 with inherited retinal disorders. All participants underwent panel-based genetic testing.RESULTS: The diagnostic yield of genetic testing for the cohort was 64% (ranging from 39% to 91% depending on the condition). The test result led to altered management (including preventing additional investigations or resulting in the introduction of personalized surveillance measures) in 33% of probands (75% for ectopia lentis, 50% for cataracts, 33% for inherited retinal disorders, 7% for anterior segment dysgenesis, 3% for albinism).CONCLUSION: Genetic testing helped identify an etiological diagnosis in the majority of preschool children with IEDs. This prevented additional unnecessary testing and provided the opportunity for anticipatory guidance in significant subsets of patients.

AB - PURPOSE: A key property to consider in all genetic tests is clinical utility, the ability of the test to influence patient management and health outcomes. Here we assess the current clinical utility of genetic testing in diverse pediatric inherited eye disorders (IEDs).METHODS: Two hundred one unrelated children (0-5 years old) with IEDs were ascertained through the database of the North West Genomic Laboratory Hub, Manchester, UK. The cohort was collected over a 7-year period (2011-2018) and included 74 children with bilateral cataracts, 8 with bilateral ectopia lentis, 28 with bilateral anterior segment dysgenesis, 32 with albinism, and 59 with inherited retinal disorders. All participants underwent panel-based genetic testing.RESULTS: The diagnostic yield of genetic testing for the cohort was 64% (ranging from 39% to 91% depending on the condition). The test result led to altered management (including preventing additional investigations or resulting in the introduction of personalized surveillance measures) in 33% of probands (75% for ectopia lentis, 50% for cataracts, 33% for inherited retinal disorders, 7% for anterior segment dysgenesis, 3% for albinism).CONCLUSION: Genetic testing helped identify an etiological diagnosis in the majority of preschool children with IEDs. This prevented additional unnecessary testing and provided the opportunity for anticipatory guidance in significant subsets of patients.

KW - Cataract/diagnosis

KW - Child, Preschool

KW - Eye

KW - Eye Abnormalities/genetics

KW - Genetic Testing

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Retinal Diseases/diagnosis

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U2 - 10.1038/s41436-019-0722-8

DO - 10.1038/s41436-019-0722-8

M3 - Article

C2 - 31848469

SN - 1098-3600

VL - 22

SP - 745

EP - 751

JO - Genetics in Medicine

JF - Genetics in Medicine

IS - 4

ER -

Clinical utility of genetic testing in 201 preschool children with inherited eye disorders

Abstract

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Transforming the management of people with inherited eye disorders: a paradigm for the implementation of genomic medicine

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Clinical utility of genetic testing in 201 preschool children with inherited eye disorders

Abstract

Keywords

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Transforming the management of people with inherited eye disorders: a paradigm for the implementation of genomic medicine

Cite this