2,832 results match your criteria Genetics in Medicine [Journal]


Mutant RAMP2 causes primary open-angle glaucoma via the CRLR-cAMP axis.

Genet Med 2019 Apr 19. Epub 2019 Apr 19.

The Key Laboratory for Human Disease Gene Study of Sichuan Province and Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.

Purpose: Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide and mutations in known genes can only explain 5-6% of POAG. This study was conducted to identify novel POAG-causing genes and explore the pathogenesis of this disease.

Methods: Exome sequencing was performed in a Han Chinese cohort comprising 398 sporadic cases with POAG and 2010 controls, followed by replication studies by Sanger sequencing. Read More

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http://www.nature.com/articles/s41436-019-0507-0
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http://dx.doi.org/10.1038/s41436-019-0507-0DOI Listing
April 2019
1 Read

Pancreatic cancer and melanoma related perceptions and behaviors following disclosure of CDKN2A variant status as a research result.

Genet Med 2019 Apr 17. Epub 2019 Apr 17.

Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, Mayo Clinic, Rochester, MN, USA.

Purpose: This study examined whether participants who learned research results related to a germline CDKN2A variant known to be associated with increased risk of pancreatic cancer and malignant melanoma would pursue confirmatory testing and cancer screening, share the genetic information with health care providers and family, and change risk perceptions.

Methods: Participants were pancreas research registry enrollees whose biological sample was tested in a research laboratory for the variant. In total, 133 individuals were invited to learn a genetic research result and participate in a study about the disclosure process. Read More

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http://www.nature.com/articles/s41436-019-0517-y
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http://dx.doi.org/10.1038/s41436-019-0517-yDOI Listing
April 2019
1 Read

Aberrant DNA methylation as a diagnostic biomarker of diabetic embryopathy.

Genet Med 2019 Apr 17. Epub 2019 Apr 17.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Purpose: Maternal diabetes is a known teratogen that can cause a wide spectrum of birth defects, collectively referred to as diabetic embryopathy (DE). However, the pathogenic mechanisms underlying DE remain uncertain and there are no definitive tests to establish the diagnosis. Here, we explore the potential of DNA methylation as a diagnostic biomarker for DE and to inform disease pathogenesis. Read More

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http://www.nature.com/articles/s41436-019-0516-z
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http://dx.doi.org/10.1038/s41436-019-0516-zDOI Listing
April 2019
1 Read
7.329 Impact Factor

Research participants' preferences for receiving genetic risk information: a discrete choice experiment.

Genet Med 2019 Apr 17. Epub 2019 Apr 17.

Centre for Research Ethics & Bioethics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.

Purpose: This study aims to determine research participants' preferences for receiving genetic risk information when participating in a scientific study that uses genome sequencing.

Methods: A discrete choice experiment questionnaire was sent to 650 research participants (response rate 60.5%). Read More

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http://dx.doi.org/10.1038/s41436-019-0511-4DOI Listing

PIGT-CDG, a disorder of the glycosylphosphatidylinositol anchor: description of 13 novel patients and expansion of the clinical characteristics.

Genet Med 2019 Apr 12. Epub 2019 Apr 12.

Danish Epilepsy Centre, Dianalund, Denmark.

Purpose: To provide a detailed electroclinical description and expand the phenotype of PIGT-CDG, to perform genotype-phenotype correlation, and to investigate the onset and severity of the epilepsy associated with the different genetic subtypes of this rare disorder. Furthermore, to use computer-assisted facial gestalt analysis in PIGT-CDG and to the compare findings with other glycosylphosphatidylinositol (GPI) anchor deficiencies.

Methods: We evaluated 13 children from eight unrelated families with homozygous or compound heterozygous pathogenic variants in PIGT. Read More

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http://www.nature.com/articles/s41436-019-0512-3
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http://dx.doi.org/10.1038/s41436-019-0512-3DOI Listing
April 2019
2 Reads

Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests.

Genet Med 2019 Apr 12. Epub 2019 Apr 12.

BGI Genomics, BGI-Shenzhen, Shenzhen, Guangdong, China.

Purpose: Multiple chromosomal aneuploidies may be associated with maternal malignancies and can cause failure of noninvasive prenatal screening (NIPS) tests. However, multiple chromosomal aneuploidies show poor specificity and selectivity for diagnosing maternal malignancies.

Methods: This multicenter retrospective analysis evaluated 639 pregnant women who tested positive for multiple chromosomal aneuploidies on initial NIPS test between January 2016 and December 2017. Read More

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http://dx.doi.org/10.1038/s41436-019-0510-5DOI Listing
April 2019
1 Read

CRISPR in the North American popular press.

Genet Med 2019 Apr 12. Epub 2019 Apr 12.

Faculty of Law and School of Public Health, Health Law Institute, University of Alberta, Edmonton, AB, Canada.

Purpose: CRISPR is often called one of the century's most important discoveries and is commonly discussed in terms of its momentous potential impacts. This study analyzed how CRISPR is discussed in the North American popular press, including how it is defined, and which benefits and risks/concerns are attributed to the technology.

Methods: Using the Factiva database, we identified 228 relevant, nonduplicated articles containing either "CRISPR" or "C. Read More

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http://dx.doi.org/10.1038/s41436-019-0482-5DOI Listing

Letter: Relearning the 3 R's? Reinterpretation, recontact, and return of genetic variants.

Genet Med 2019 Apr 11. Epub 2019 Apr 11.

Centre of Genomics and Policy, McGill University, Montreal, QC, Canada.

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http://dx.doi.org/10.1038/s41436-019-0494-1DOI Listing

Commentary: Expanded carrier screening: how much is too much?

Genet Med 2019 Apr 11. Epub 2019 Apr 11.

Women's Service, Ochsner Health System, New Orleans, LA, USA.

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http://dx.doi.org/10.1038/s41436-019-0514-1DOI Listing

Response to Knoppers et al.

Genet Med 2019 Apr 11. Epub 2019 Apr 11.

Division of Translational Medicine and Human Genetics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

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http://dx.doi.org/10.1038/s41436-019-0496-zDOI Listing

Variant classification changes over time in BRCA1 and BRCA2.

Genet Med 2019 Apr 11. Epub 2019 Apr 11.

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.

Purpose: To report BRCA1 and BRCA2 (BRCA1/2) variant reassessments and reclassifications between 2012 and 2017 at the Advanced Molecular Diagnostics Laboratory (AMDL) in Toronto, Canada, which provides BRCA1/2 testing for patients in Ontario, and to compare AMDL variant classifications with submissions in ClinVar.

Methods: Variants were assessed using a standardized variant assessment tool based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology's guidelines and tracked in an in-house database. Variants were shared through the Canadian Open Genetics Repository and submitted to ClinVar for comparison against other laboratories. Read More

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http://dx.doi.org/10.1038/s41436-019-0493-2DOI Listing
April 2019
7.329 Impact Factor

ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder.

Genet Med 2019 Apr 10. Epub 2019 Apr 10.

Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA.

Purpose: To identify the molecular cause in five unrelated families with a distinct autosomal dominant ocular systemic disorder we called ROSAH syndrome due to clinical features of retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache.

Methods: Independent discovery exome and genome sequencing in families 1, 2, and 3, and confirmation in families 4 and 5. Expression of wild-type messenger RNA and protein in human and mouse tissues and cell lines. Read More

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http://www.nature.com/articles/s41436-019-0476-3
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http://dx.doi.org/10.1038/s41436-019-0476-3DOI Listing
April 2019
4 Reads
7.329 Impact Factor

All-cause mortality and survival in adults with 22q11.2 deletion syndrome.

Genet Med 2019 Apr 5. Epub 2019 Apr 5.

Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON, Canada.

Purpose: Given limited data available on long-term outcomes in 22q11.2 deletion syndrome (22q11.2DS), we investigated mortality risk in adults with this microdeletion syndrome. Read More

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http://dx.doi.org/10.1038/s41436-019-0509-yDOI Listing
April 2019
2 Reads

Successful recruitment and retention of diverse participants in a genomics clinical trial: a good invitation to a great party.

Genet Med 2019 Apr 5. Epub 2019 Apr 5.

Center for Health Equity and Community Engaged Research and Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Purpose: African ancestry (AA) individuals are inadequately included in translational genomics research, limiting generalizability of findings and benefits of genomic discoveries for populations already facing disproportionately poor health outcomes. We aimed to determine the impact of stakeholder-engaged strategies on recruitment and retention of AA adult patients into a clinical trial testing them for renal risk variants nearly exclusive to AAs.

Methods: Our academic-clinical-community team developed ten key strategies that recognize AAs' barriers and facilitators for participation. Read More

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http://dx.doi.org/10.1038/s41436-019-0498-xDOI Listing
April 2019
1 Read

A high-resolution X chromosome copy-number variation map in fertile females and women with primary ovarian insufficiency.

Genet Med 2019 Apr 5. Epub 2019 Apr 5.

Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.

Purpose: Sex-biased expression of genes on the X chromosome is accomplished by a complex mechanism of dosage regulation that leads to anatomical and physiological differences between males and females. Copy-number variations (CNVs) may impact the human genome by either affecting gene dosage or disturbing a chromosome structural and/or functional integrity.

Methods: We performed a high-resolution CNV profiling to investigate the X chromosome integrity in cohorts of 269 fertile females and 111 women affected with primary ovarian insufficiency (POI) and assessed CNVs impact into functional and nonfunctional genomic elements. Read More

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http://www.nature.com/articles/s41436-019-0505-2
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http://dx.doi.org/10.1038/s41436-019-0505-2DOI Listing
April 2019
10 Reads

Correction: Clinical and genetic spectrum of children with congenital diarrhea and enteropathy in China.

Genet Med 2019 Apr 4. Epub 2019 Apr 4.

Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China.

There is an error in the figure legend of Figure 1(a). The correct figure legend for this figure should be "Fig.1 (a) Hematoxylin and eosin (H&E) analysis of the descending duodenum shows the loss of goblet cells and Paneth cells and the presence of apoptotic cells in patient 48. Read More

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http://dx.doi.org/10.1038/s41436-019-0513-2DOI Listing

Correction: Population genomic screening of all young adults in a health-care system: a cost-effectiveness analysis.

Genet Med 2019 Apr 4. Epub 2019 Apr 4.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

In the original version of this Article, the affiliation details for Lei Zhang were given as Monash University. While working on the Article Dr. Zhang was also affiliated with the Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, PR China. Read More

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http://dx.doi.org/10.1038/s41436-019-0515-0DOI Listing
April 2019
7.329 Impact Factor

Biallelic loss-of-function P4HTM gene variants cause hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy, and eye abnormalities (HIDEA syndrome).

Genet Med 2019 Apr 3. Epub 2019 Apr 3.

PEDEGO Research Unit and Medical Research Centre Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland.

Purpose: A new syndrome with hypotonia, intellectual disability, and eye abnormalities (HIDEA) was previously described in a large consanguineous family. Linkage analysis identified the recessive disease locus, and genome sequencing yielded three candidate genes with potentially pathogenic biallelic variants: transketolase (TKT), transmembrane prolyl 4-hydroxylase (P4HTM), and ubiquitin specific peptidase 4 (USP4). However, the causative gene remained elusive. Read More

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http://www.nature.com/articles/s41436-019-0503-4
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http://dx.doi.org/10.1038/s41436-019-0503-4DOI Listing
April 2019
3 Reads

Adherence of cell-free DNA noninvasive prenatal screens to ACMG recommendations.

Genet Med 2019 Apr 3. Epub 2019 Apr 3.

Departments of Obstetrics and Gynecology and Maternal Fetal Medicine, Baylor University Medical Center, Dallas, TX, USA.

Purpose: Noninvasive prenatal screening (NIPS) for fetal aneuploidy via cell-free DNA has been commercially available in the United States since 2011. In 2016, the American College of Medical Genetics and Genomics (ACMG) issued a position statement with specific recommendations for testing laboratories. We sought to evaluate adherence to these recommendations. Read More

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http://dx.doi.org/10.1038/s41436-019-0485-2DOI Listing
April 2019
2 Reads

Evaluation of the cost and effectiveness of diverse recruitment methods for a genetic screening study.

Genet Med 2019 Apr 1. Epub 2019 Apr 1.

Department of Medicine, Columbia University Medical Center, New York, NY, USA.

Purpose: Recruitment of participants from diverse backgrounds is crucial to the generalizability of genetic research, but has proven challenging. We retrospectively evaluated recruitment methods used for a study on return of genetic results.

Methods: The costs of study design, development, and participant enrollment were calculated, and the characteristics of the participants enrolled through the seven recruitment methods were examined. Read More

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http://dx.doi.org/10.1038/s41436-019-0497-yDOI Listing
April 2019
1 Read
7.329 Impact Factor

Challenges and lessons learned from clinical pharmacogenetic implementation of multiple gene-drug pairs across ambulatory care settings.

Genet Med 2019 Mar 30. Epub 2019 Mar 30.

Department of Pharmacotherapy and Translational Research, University of Florida College of Pharmacy, Gainesville, FL, USA.

Purpose: Incorporating a patient's genotype into the clinical decision-making process is one approach to precision medicine. The University of Florida (UF) Health Precision Medicine Program is a pharmacist-led multidisciplinary effort that has led the clinical implementation of six gene-drug(s) pairs to date. This study focuses on the challenges encountered and lessons learned with implementing pharmacogenetic testing for three of these: CYP2D6-opioids, CYP2D6/CYP2C19-selective serotonin reuptake inhibitors, and CYP2C19-proton pump inhibitors within six pragmatic clinical trials at UF Health and partners. Read More

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http://dx.doi.org/10.1038/s41436-019-0500-7DOI Listing

A case-control collapsing analysis identifies retinal dystrophy genes associated with ophthalmic disease in patients with no pathogenic ABCA4 variants.

Genet Med 2019 Mar 30. Epub 2019 Mar 30.

Department of Ophthalmology, Columbia University, New York, NY, USA.

Purpose: Variants in the ABCA4 gene are causal for a variety of retinal dystrophy phenotypes, including Stargardt disease (STGD1). However, 15% of patients who present with symptoms compatible with STGD1/ABCA4 disease do not have identifiable causal ABCA4 variants. We hypothesized that a case-control collapsing analysis in ABCA4-negative patients with compatible symptoms would provide an objective measure to identify additional disease genes. Read More

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http://dx.doi.org/10.1038/s41436-019-0495-0DOI Listing

De novo and biallelic DEAF1 variants cause a phenotypic spectrum.

Genet Med 2019 Mar 29. Epub 2019 Mar 29.

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Purpose: To investigate the effect of different DEAF1 variants on the phenotype of patients with autosomal dominant and recessive inheritance patterns and on DEAF1 activity in vitro.

Methods: We assembled a cohort of 23 patients with de novo and biallelic DEAF1 variants, described the genotype-phenotype correlation, and investigated the differential effect of de novo and recessive variants on transcription assays using DEAF1 and Eif4g3 promoter luciferase constructs.

Results: The proportion of the most prevalent phenotypic features, including intellectual disability, speech delay, motor delay, autism, sleep disturbances, and a high pain threshold, were not significantly different in patients with biallelic and pathogenic de novo DEAF1 variants. Read More

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http://dx.doi.org/10.1038/s41436-019-0473-6DOI Listing
March 2019
1 Read

Mobility in osteogenesis imperfecta: a multicenter North American study.

Genet Med 2019 Mar 28. Epub 2019 Mar 28.

Orthopaedic Rehabilitation and Engineering Center, Marquette University, Milwaukee, WI, USA.

Purpose: Osteogenesis imperfecta (OI) is a genetic connective tissue disorder that causes bone fragility. Phenotypic severity influences ability to walk, however, little is known about ambulatory characteristics of individuals with OI, especially in more severe forms. The purpose of this work was to characterize mobility in OI using standard clinical assessment tools and determine if patient characteristics could be used to predict mobility outcomes. Read More

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http://dx.doi.org/10.1038/s41436-019-0491-4DOI Listing
March 2019
2 Reads

The Manchester International Consensus Group recommendations for the management of gynecological cancers in Lynch syndrome.

Genet Med 2019 Mar 28. Epub 2019 Mar 28.

Prevention Early Detection Theme, NIHR Biomedical Research Centre, The Christie NHS Foundation Trust, Manchester, UK.

Purpose: There are no internationally agreed upon clinical guidelines as to which women with gynecological cancer would benefit from Lynch syndrome screening or how best to manage the risk of gynecological cancer in women with Lynch syndrome. The Manchester International Consensus Group was convened in April 2017 to address this unmet need. The aim of the Group was to develop clear and comprehensive clinical guidance regarding the management of the gynecological sequelae of Lynch syndrome based on existing evidence and expert opinion from medical professionals and patients. Read More

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http://dx.doi.org/10.1038/s41436-019-0489-yDOI Listing
March 2019
7.329 Impact Factor

From diagnostic yield to clinical impact: a pilot study on the implementation of prenatal exome sequencing in routine care.

Genet Med 2019 Mar 28. Epub 2019 Mar 28.

Department of Clinical Genetics, Leiden University Medical Centre, Leiden, the Netherlands.

Purpose: Exome sequencing (ES) is an efficient tool to diagnose genetic disorders postnatally. Recent studies show that it may have a considerable diagnostic yield in fetuses with structural anomalies on ultrasound. We report on the clinical impact of the implementation of prenatal ES (pES) for ongoing pregnancies in routine care. Read More

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http://dx.doi.org/10.1038/s41436-019-0499-9DOI Listing

What do we do now?: Responding to claims of germline gene editing in humans.

Genet Med 2019 Mar 27. Epub 2019 Mar 27.

Department of Genetics and Stanford Center for Biomedical Ethics, Stanford School of Medicine, Stanford, CA, USA.

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http://dx.doi.org/10.1038/s41436-019-0492-3DOI Listing

Disability inclusion in precision medicine research: a first national survey.

Genet Med 2019 Mar 22. Epub 2019 Mar 22.

Center for Research on Ethical, Legal & Social Implications of Psychiatric, Neurologic & Behavioral Genetics, Department of Psychiatry, Columbia University, New York, NY, USA.

Purpose: Including people with disabilities in precision medicine research (PMR) is key for increasing cohorts' diversity, improving understanding of population health, and attaining social justice for the United States' largest health disparities group. We conducted a national survey to explore the views of people with disabilities about PMR.

Methods: An online survey was developed in disability-accessible formats. Read More

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http://dx.doi.org/10.1038/s41436-019-0486-1DOI Listing
March 2019
4 Reads
7.329 Impact Factor

Clinical characteristics of 248 patients with Krabbe disease: quantitative natural history modeling based on published cases.

Genet Med 2019 Mar 22. Epub 2019 Mar 22.

Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.

Purpose: Krabbe disease (OMIM 245200) is an orphan neurometabolic disorder caused by a deficiency of the lysosomal enzyme galactocerebrosidase (GALC). Hard clinical endpoints and biomarker-phenotype correlations are useful for future clinical trials.

Methods: We performed a quantitative analysis of published cases (N = 248) with Krabbe disease, stratified by age at disease onset: early infantile (age 0-6 months), late infantile (age 7-36 months), juvenile/adolescent (age 37-180 months), and adult onset (>180 months). Read More

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http://dx.doi.org/10.1038/s41436-019-0480-7DOI Listing
March 2019
1 Read

Correction: Toward automation of germline variant curation in clinical cancer genetics.

Genet Med 2019 Mar 21. Epub 2019 Mar 21.

Niehaus Center For Inherited Cancer Genomics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

An update to the original published conflict of interest for author Liying Zhang, PhD. L.Z. Read More

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http://dx.doi.org/10.1038/s41436-019-0490-5DOI Listing
March 2019
1 Read

A retrospective review of multiple findings in diagnostic exome sequencing: half are distinct and half are overlapping diagnoses.

Genet Med 2019 Mar 21. Epub 2019 Mar 21.

Clinical Genomics, Ambry Genetics, Aliso Viejo, CA, USA.

Purpose: We evaluated clinical and genetic features enriched in patients with multiple Mendelian conditions to determine which patients are more likely to have multiple potentially relevant genetic findings (MPRF).

Methods: Results of the first 7698 patients who underwent exome sequencing at Ambry Genetics were reviewed. Clinical and genetic features were examined and degree of phenotypic overlap between the genetic diagnoses was evaluated. Read More

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http://dx.doi.org/10.1038/s41436-019-0477-2DOI Listing
March 2019
2 Reads

Clinical and genetic spectrum of children with congenital diarrhea and enteropathy in China.

Genet Med 2019 Mar 21. Epub 2019 Mar 21.

Department of Neonatology, Children's Hospital of Fudan University, Shanghai, China.

Purpose: Genetic sequencing for children with congenital diarrhea and enteropathy (CODE) has important implications for the diagnosis, prognosis, and implementation of precision medicine.

Methods: We performed exome sequencing or targeted panel sequencing on 137 children with CODE. Endoscopic, imaging, histological, and immunological assessments were also applied. Read More

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http://dx.doi.org/10.1038/s41436-019-0488-zDOI Listing
March 2019
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Multi-site investigation of strategies for the clinical implementation of CYP2D6 genotyping to guide drug prescribing.

Genet Med 2019 Mar 21. Epub 2019 Mar 21.

Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA.

Purpose: A number of institutions have clinically implemented CYP2D6 genotyping to guide drug prescribing. We compared implementation strategies of early adopters of CYP2D6 testing, barriers faced by both early adopters and institutions in the process of implementing CYP2D6 testing, and approaches taken to overcome these barriers.

Methods: We surveyed eight early adopters of CYP2D6 genotyping and eight institutions in the process of adoption. Read More

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http://dx.doi.org/10.1038/s41436-019-0484-3DOI Listing

Rethinking the "open future" argument against predictive genetic testing of children.

Genet Med 2019 Mar 21. Epub 2019 Mar 21.

Department of Pediatrics, University of Louisville, Louisville, KY, USA.

Professional consensus has traditionally discouraged predictive genetic testing when no childhood interventions can reduce future morbidity or mortality. However, advances in genome sequencing and accumulating evidence that children and families cope adequately with predictive genetic information have weakened this consensus. The primary argument remaining against testing appeals to children's "right to an open future. Read More

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http://dx.doi.org/10.1038/s41436-019-0483-4DOI Listing

ClinGen expert clinical validity curation of 164 hearing loss gene-disease pairs.

Genet Med 2019 Mar 21. Epub 2019 Mar 21.

Laboratory for Molecular Medicine, Partners Healthcare Personalized Medicine, Cambridge, MA, USA.

Purpose: Proper interpretation of genomic variants is critical to successful medical decision making based on genetic testing results. A fundamental prerequisite to accurate variant interpretation is the clear understanding of the clinical validity of gene-disease relationships. The Clinical Genome Resource (ClinGen) has developed a semiquantitative framework to assign clinical validity to gene-disease relationships. Read More

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http://dx.doi.org/10.1038/s41436-019-0487-0DOI Listing
March 2019
7.329 Impact Factor

Nationwide population genetic screening improves outcomes of newborn screening for hearing loss in China.

Genet Med 2019 Mar 20. Epub 2019 Mar 20.

BGI Genomics, BGI-Shenzhen, Shenzhen, China.

Purpose: The benefits of concurrent newborn hearing and genetic screening have not been statistically proven due to limited sample sizes and outcome data. To fill this gap, we analyzed outcomes of newborns with genetic screening results.

Methods: Newborns in China were screened for 20 hearing-loss-related genetic variants from 2012 to 2017. Read More

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http://dx.doi.org/10.1038/s41436-019-0481-6DOI Listing

Atlas-CNV: a validated approach to call single-exon CNVs in the eMERGESeq gene panel.

Genet Med 2019 Mar 20. Epub 2019 Mar 20.

Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.

Purpose: To provide a validated method to confidently identify exon-containing copy-number variants (CNVs), with a low false discovery rate (FDR), in targeted sequencing data from a clinical laboratory with particular focus on single-exon CNVs.

Methods: DNA sequence coverage data are normalized within each sample and subsequently exonic CNVs are identified in a batch of samples, when the target log ratio of the sample to the batch median exceeds defined thresholds. The quality of exonic CNV calls is assessed by C-scores (Z-like scores) using thresholds derived from gold standard samples and simulation studies. Read More

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http://dx.doi.org/10.1038/s41436-019-0475-4DOI Listing
March 2019
1 Read

Correction: Analysis of fetal DNA in maternal plasma with markers designed for forensic DNA mixture resolution.

Genet Med 2019 Mar 11. Epub 2019 Mar 11.

Unité de Génétique Forensique, Centre Universitaire Romand de Médecine Légale, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland.

In the original version of this Article, the data for Mother ID 8; 13; 25; 31; and 47 of Table 2 was merged. This has now been corrected in both the PDF and HTML versions of the Article. Read More

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http://dx.doi.org/10.1038/s41436-019-0465-6DOI Listing

Carrier frequency estimation of Zellweger spectrum disorder using ExAC database and bioinformatics tools.

Genet Med 2019 Mar 8. Epub 2019 Mar 8.

Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Purpose: We aimed to estimate the carrier frequency of Zellweger spectrum disorder (ZSD), a rare autosomal recessive disease, and the associated disease incidence based on data from the Exome Aggregation Consortium (ExAC) of approximately 60,000 individuals.

Methods: We obtained variants from ExAC in 13 PEX genes associated with ZSD. Potentially pathogenic missense variants were identified with computational variant analysis tools according to three stringency levels. Read More

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http://dx.doi.org/10.1038/s41436-019-0468-3DOI Listing

Estimating yields of prenatal carrier screening and implications for design of expanded carrier screening panels.

Genet Med 2019 Mar 8. Epub 2019 Mar 8.

Department of Obstetrics and Gynecology, Baylor University Medical Center, Dallas, TX, 75246, USA.

Purpose: Prenatal genetic carrier screening can identify parents at risk of having a child affected by a recessive condition. However, the conditions/genes most appropriate for screening remain a matter of debate. Estimates of carrier rates across genes are needed to guide construction of carrier screening panels. Read More

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http://dx.doi.org/10.1038/s41436-019-0472-7DOI Listing

Elucidation of the phenotypic spectrum and genetic landscape in primary and secondary microcephaly.

Genet Med 2019 Mar 7. Epub 2019 Mar 7.

Institute of Medical Genetics, University of Zurich, Schlieren, Zurich, Switzerland.

Purpose: Microcephaly is a sign of many genetic conditions but has been rarely systematically evaluated. We therefore comprehensively studied the clinical and genetic landscape of an unselected cohort of patients with microcephaly.

Methods: We performed clinical assessment, high-resolution chromosomal microarray analysis, exome sequencing, and functional studies in 62 patients (58% with primary microcephaly [PM], 27% with secondary microcephaly [SM], and 15% of unknown onset). Read More

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http://www.nature.com/articles/s41436-019-0464-7
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http://dx.doi.org/10.1038/s41436-019-0464-7DOI Listing
March 2019
10 Reads

The transformation of medical genetics by clinical genomics: hubris meets humility.

Authors:
Wayne W Grody

Genet Med 2019 Mar 7. Epub 2019 Mar 7.

Divisions of Medical Genetics and Molecular Diagnostics, Departments of Path. & Lab. Medicine, Pediatrics, and Human Genetics, UCLA School of Medicine, UCLA Institute for Society and Genetics, Molecular Diagnostic Laboratories and Clinical Genomics Center, UCLA Medical Center, Los Angeles, CA, USA.

There is no question that the advent of massively parallel ("next-generation") DNA sequencing has thrust Medical Genetics and Molecular Diagnostics into a new era, availing practitioners and patients of a form of genetic testing unprecedented in its scope and comprehensiveness. It has produced impressive diagnostic yield, ended the "diagnostic odyssey" for many patients and families, expanded the known phenotypes of countless disorders, and led to almost weekly new disease gene discoveries. Nevertheless, it still fails to identify the molecular cause of many patients who clearly exhibit genetic/syndromic conditions, while at the same time unmasking other sequence changes of uncertain significance or unexpected consequences. Read More

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http://dx.doi.org/10.1038/s41436-019-0450-0DOI Listing
March 2019
22 Reads

Atypical COL3A1 variants (glutamic acid to lysine) cause vascular Ehlers-Danlos syndrome with a consistent phenotype of tissue fragility and skin hyperextensibility.

Genet Med 2019 Mar 6. Epub 2019 Mar 6.

Ehlers-Danlos Syndrome National Diagnostic Service London, North West Thames Regional Genetics Service, London North West Healthcare University NHS Trust, Harrow, Middlesex, UK.

Purpose: The Ehlers-Danlos syndromes (EDS) are a group of rare inherited connective tissue disorders. Vascular EDS (vEDS) is caused by pathogenic variants in COL3A1, most frequently glycine substitutions. We describe the phenotype of the largest series of vEDS patients with glutamic acid to lysine substitutions (Glu>Lys) in COL3A1, which were all previously considered to be variants of unknown significance. Read More

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http://dx.doi.org/10.1038/s41436-019-0470-9DOI Listing
March 2019
2 Reads
7.329 Impact Factor

Clinical utility of noninvasive prenatal screening for expanded chromosome disease syndromes.

Genet Med 2019 Mar 4. Epub 2019 Mar 4.

Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.

Purpose: To assess the clinical performance of an expanded noninvasive prenatal screening (NIPS) test ("NIPS-Plus") for detection of both aneuploidy and genome-wide microdeletion/microduplication syndromes (MMS).

Methods: A total of 94,085 women with a singleton pregnancy were prospectively enrolled in the study. The cell-free plasma DNA was directly sequenced without intermediate amplification and fetal abnormalities identified using an improved copy-number variation (CNV) calling algorithm. Read More

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http://dx.doi.org/10.1038/s41436-019-0467-4DOI Listing
March 2019
2 Reads
7.329 Impact Factor

Response to Wang et al.

Genet Med 2019 Mar 1. Epub 2019 Mar 1.

Department of Pediatrics and Medicine, Columbia University, New York, NY, USA.

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http://dx.doi.org/10.1038/s41436-019-0469-2DOI Listing
March 2019
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A data-driven evaluation of the size and content of expanded carrier screening panels.

Genet Med 2019 Feb 28. Epub 2019 Feb 28.

Myriad Women's Health, Inc. (formerly Counsyl, Inc.), South San Francisco, CA, USA.

Purpose: The American College of Obstetricians and Gynecologists (ACOG) proposed seven criteria for expanded carrier screening (ECS) panel design. To ensure that screening for a condition is sufficiently sensitive to identify carriers and reduce residual risk of noncarriers, one criterion requires a per-condition carrier rate greater than 1 in 100. However, it is unestablished whether this threshold corresponds with a loss in clinical detection. Read More

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http://dx.doi.org/10.1038/s41436-019-0466-5DOI Listing
February 2019
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Response to Roberts et al. 2018: cohort ascertainment and methods of analysis impact the association between cancer and genetic predisposition - the tale of breast cancer risk and Lynch syndrome genes MSH6/PMS2.

Genet Med 2019 Feb 28. Epub 2019 Feb 28.

Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

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http://dx.doi.org/10.1038/s41436-019-0471-8DOI Listing
February 2019
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Correction: Experiences and perspectives on the return of secondary findings among genetic epidemiologists.

Genet Med 2019 Feb 22. Epub 2019 Feb 22.

Department of Bioethics, Case Western Reserve University, Cleveland, OH, USA.

In the original published version of Table 2 the number of respondents who said "No" to the question "Does your consent form distinguish between targeted and incidental findings?" was indicated as "4." It should have read "44." This has now been corrected in both the PDF and HTML versions of the Article. Read More

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http://dx.doi.org/10.1038/s41436-019-0462-9DOI Listing
February 2019

Correction: BOADICEA: a comprehensive breast cancer risk prediction model incorporating genetic and nongenetic risk factors.

Genet Med 2019 Feb 21. Epub 2019 Feb 21.

Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, The Strangeways Research Laboratory, University of Cambridge, Cambridge, UK.

This has now been corrected in both the PDF and HTML versions of the Article. The authors regret this error. Read More

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http://dx.doi.org/10.1038/s41436-019-0459-4DOI Listing
February 2019
1 Read