Abstract:
:Secondary genomic findings are increasingly being returned to individuals as opportunistic screening results. A secondary finding offers the chance to identify and mitigate disease that may otherwise be unrecognized in an individual. As a form of screening, secondary findings must be considered differently from sequencing results in a diagnostic setting. For these reasons, clinicians should employ an evaluation and long-term management strategy that accounts for both the increased disease risk associated with a secondary finding and the lower positive predictive value of a screening result compared to an indication-based testing result. Here we describe an approach to the clinical evaluation and management of an individual who presents with a secondary finding. This approach enumerates five domains of evaluation-(1) medical history, (2) physical exam, (3) family history, (4) diagnostic phenotypic testing, and (5) variant correlation-through which a clinician can distinguish a molecular finding from a clinicomolecular diagnosis of genomic disease. With this framework, both geneticists and non-geneticist clinicians can optimize their ability to detect and mitigate genomic disease while avoiding the pitfalls of overdiagnosis. Our goal with this approach is to help clinicians translate secondary findings into meaningful recognition, treatment, and prevention of disease.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Katz AE,Nussbaum RL,Solomon BD,Rehm HL,Williams MS,Biesecker LGdoi
10.1016/j.ajhg.2020.05.002subject
Has Abstractpub_date
2020-07-02 00:00:00pages
3-14issue
1eissn
0002-9297issn
1537-6605pii
S0002-9297(20)30149-Xjournal_volume
107pub_type
杂志文章,评审abstract::Joubert syndrome (JBTS) is an autosomal-recessive disorder characterized by a distinctive mid-hindbrain malformation, developmental delay with hypotonia, ocular-motor apraxia, and breathing abnormalities. Although JBTS was first described more than 40 years ago in French Canadian siblings, the causal mutations have no...
journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 杂志文章
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract::A high incidence of 46,XX true hermaphroditism exists among southern African blacks. The gonadal distribution and clinical presentation of 38 patients are described. The aim of our study on 11 families with histologically proven XX true hermaphroditism was to determine whether a common genetic or environmental etiolog...
journal_title:American journal of human genetics
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doi:
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abstract::Transthyretin (TTR) (122 Val----Ile), caused by a point mutation which destroys a MaeIII restriction site, is associated with cardiac amyloidosis in black individuals. To estimate the frequency of the MaeIII(-) gene in the black population without overt cardiac disease, DNA from 177 black individuals without amyloidos...
journal_title:American journal of human genetics
pub_type: 杂志文章,评审
doi:
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2012.08.004
更新日期:2012-09-07 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2011.01.019
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1981-03-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1976-05-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2019.07.007
更新日期:2019-09-05 00:00:00
abstract::The critical importance of cytoskeletal function for correct neuronal migration during development of the cerebral cortex has been underscored by the identities of germline mutations underlying a number of human neurodevelopmental disorders. The proteins affected include TUBA1A, a major alpha-tubulin isoform, and micr...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2009.10.007
更新日期:2009-11-01 00:00:00
abstract::Low serum HDL-cholesterol (HDL-C) is a major risk factor for coronary artery disease. We performed targeted genotyping of a 12.4 Mb linked region on 16q to test for association with low HDL-C by using a regional-tag SNP strategy. We identified one SNP, rs2548861, in the WW-domain-containing oxidoreductase (WWOX) gene ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2008.07.002
更新日期:2008-08-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.01.018
更新日期:2018-03-01 00:00:00
abstract::RNA sequencing (RNA-seq) is gaining popularity as a complementary assay to genome sequencing for precisely identifying the molecular causes of rare disorders. A powerful approach is to identify aberrant gene expression levels as potential pathogenic events. However, existing methods for detecting aberrant read counts ...
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pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.10.025
更新日期:2018-12-06 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/422013
更新日期:2004-07-01 00:00:00
abstract::The risk of epilepsy among individuals with intellectual disability (ID) is approximately ten times that of the general population. From a cohort of >5,000 families affected by neurodevelopmental disorders, we identified six consanguineous families harboring homozygous inactivating variants in MBOAT7, encoding lysopho...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2016.07.019
更新日期:2016-10-06 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 杂志文章,meta分析
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journal_title:American journal of human genetics
pub_type: 杂志文章
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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更新日期:1993-11-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
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