2,780 results match your criteria Genetics in Medicine [Journal]


Correction: Estimating the burden and economic impact of pediatric genetic disease.

Genet Med 2019 Feb 14. Epub 2019 Feb 14.

Illumina, Inc., 5200 Illumina Way, San Diego, CA, USA.

This Article was originally published under Nature Research's License to Publish, but has now been made available under a [CC BY-NC-ND 4.0] license. The PDF and HTML versions of the Article have been modified accordingly. Read More

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http://dx.doi.org/10.1038/s41436-019-0458-5DOI Listing
February 2019

Phenotype of CM-AVM2 caused by variants in EPHB4: how much overlap with hereditary hemorrhagic telangiectasia (HHT)?

Genet Med 2019 Feb 14. Epub 2019 Feb 14.

Department of Pathology, University of Utah, Salt Lake City, UT, USA.

Purpose: EPHB4 variants were recently reported to cause capillary malformation-arteriovenous malformation 2 (CM-AVM2). CM-AVM2 mimics RASA1-related CM-AVM1 and hereditary hemorrhagic telangiectasia (HHT), as clinical features include capillary malformations (CMs), telangiectasia, and arteriovenous malformations (AVMs). Epistaxis, another clinical feature that overlaps with HHT, was reported in several cases. Read More

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http://dx.doi.org/10.1038/s41436-019-0443-zDOI Listing
February 2019

Clinical impact and cost-effectiveness of a 176-condition expanded carrier screen.

Genet Med 2019 Feb 14. Epub 2019 Feb 14.

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

Purpose: Carrier screening identifies couples at high risk for conceiving offspring affected with serious heritable conditions. Minimal guidelines recommend offering testing for cystic fibrosis and spinal muscular atrophy, but expanded carrier screening (ECS) assesses hundreds of conditions simultaneously. Although medical societies consider ECS an acceptable practice, the health economics of ECS remain incompletely characterized. Read More

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http://dx.doi.org/10.1038/s41436-019-0455-8DOI Listing
February 2019

SERPINA1 Z allele is associated with cystic fibrosis liver disease.

Genet Med 2019 Feb 11. Epub 2019 Feb 11.

Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, Paris, France.

Purpose: The SERPINA1 Z allele is associated with cystic fibrosis (CF)-related liver disease (CFLD), a common manifestation in patients with CF. We estimated CFLD incidence based on the SERPINA1 genotype in 3328 CF patients with CFLD-phenotype information.

Methods: The associations of SERPINA1 Z (rs28929474) and S (rs17580) alleles with age at CFLD onset and the development of CFLD-related complications (severe liver disease with cirrhosis, portal hypertension, esophageal varices) were analyzed. Read More

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http://dx.doi.org/10.1038/s41436-019-0449-6DOI Listing
February 2019
1 Read

Variants in TCF20 in neurodevelopmental disability: description of 27 new patients and review of literature.

Genet Med 2019 Feb 11. Epub 2019 Feb 11.

GeneDx, Gaithersburg, MD, USA.

Purpose: To define the clinical characteristics of patients with variants in TCF20, we describe 27 patients, 26 of whom were identified via exome sequencing. We compare detailed clinical data with 17 previously reported patients.

Methods: Patients were ascertained through molecular testing laboratories performing exome sequencing (and other testing) with orthogonal confirmation; collaborating referring clinicians provided detailed clinical information. Read More

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http://dx.doi.org/10.1038/s41436-019-0454-9DOI Listing
February 2019
1 Read

Genetic diversity and pathogenic variants as possible predictors of severity in a French sample of nonsyndromic heritable thoracic aortic aneurysms and dissections (nshTAAD).

Genet Med 2019 Feb 11. Epub 2019 Feb 11.

Hôpital Bichat, Département de Génétique, Assistance Publique-Hôpitaux de Paris, Paris, France.

Purpose: Heritable thoracic aortic aneurysms and dissections (hTAAD) are life-threatening complications of well-known syndromic diseases or underdiagnosed nonsyndromic heritable forms (nshTAAD). Both have an autosomal dominant transmission and are genetically heterogeneous. Our objective was to describe the relevance of molecular diagnosis in these patients and the contribution of each gene in nshTAAD. Read More

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http://dx.doi.org/10.1038/s41436-019-0444-yDOI Listing
February 2019
1 Read
7.329 Impact Factor

CRISPR/Cas9-targeted enrichment and long-read sequencing of the Fuchs endothelial corneal dystrophy-associated TCF4 triplet repeat.

Genet Med 2019 Feb 8. Epub 2019 Feb 8.

UCL Institute of Ophthalmology, London, UK.

Purpose: To demonstrate the utility of an amplification-free long-read sequencing method to characterize the Fuchs endothelial corneal dystrophy (FECD)-associated intronic TCF4 triplet repeat (CTG18.1).

Methods: We applied an amplification-free method, utilizing the CRISPR/Cas9 system, in combination with PacBio single-molecule real-time (SMRT) long-read sequencing, to study CTG18. Read More

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http://dx.doi.org/10.1038/s41436-019-0453-xDOI Listing
February 2019

Impact of NUDT15 genetics on severe thiopurine-related hematotoxicity in patients with European ancestry.

Genet Med 2019 Feb 7. Epub 2019 Feb 7.

Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.

Purpose: Severe hematotoxicity in patients with thiopurine therapy has been associated with genetic polymorphisms in the thiopurine S-methyltransferase (TPMT). While TPMT genetic testing is clinically implemented for dose individualization, alterations in the nudix hydrolase 15 (NUDT15) emerged as independent determinant of thiopurine-related hematotoxicity. Because data for European patients are limited, we investigated the relevance of NUDT15 in Europeans. Read More

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http://dx.doi.org/10.1038/s41436-019-0448-7DOI Listing
February 2019
1 Read

Efficacy of the pharmacologic chaperone migalastat in a subset of male patients with the classic phenotype of Fabry disease and migalastat-amenable variants: data from the phase 3 randomized, multicenter, double-blind clinical trial and extension study.

Genet Med 2019 Feb 6. Epub 2019 Feb 6.

Amicus Therapeutics, Inc, Cranbury, NJ, USA.

Purpose: Outcomes in patients with Fabry disease receiving migalastat during the phase 3 FACETS trial (NCT00925301) were evaluated by phenotype.

Methods: Data were evaluated in two subgroups of patients with migalastat-amenable GLA variants: "classic phenotype" (n = 14; males with residual peripheral blood mononuclear cell α-galactosidase A <3% normal and multiorgan system involvement) and "other patients" (n = 36; males not meeting classic phenotype criteria and all females). Endpoints included estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMi), Gastrointestinal Symptoms Rating Scale diarrhea subscale (GSRS-D), renal peritubular capillary (PTC) globotriaosylceramide (GL-3) inclusions, and plasma globotriaosylsphingosine (lyso-Gb). Read More

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http://dx.doi.org/10.1038/s41436-019-0451-zDOI Listing
February 2019
1 Read

A suite of automated sequence analyses reduces the number of candidate deleterious variants and reveals a difference between probands and unaffected siblings.

Genet Med 2019 Jan 31. Epub 2019 Jan 31.

Office of the Clinical Director, National Human Genome Research Institute, and Undiagnosed Diseases Program and Network, Office of the Director, National Institutes of Health, Bethesda, MD, USA.

Purpose: Develop an automated exome analysis workflow that can produce a very small number of candidate variants yet still detect different numbers of deleterious variants between probands and unaffected siblings.

Methods: Ninety-seven outbred nuclear families from the Undiagnosed Diseases Program/Network included single probands and the corresponding unaffected sibling(s). Single-nucleotide polymorphism (SNP) chip and exome analyses were performed on all, with proband and unaffected sibling considered independently as the target. Read More

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http://www.nature.com/articles/s41436-019-0434-0
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http://dx.doi.org/10.1038/s41436-019-0434-0DOI Listing
January 2019
2 Reads

Correction: The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin-Siris syndrome.

Authors:
Pleuntje J van der Sluijs Sandra Jansen Samantha A Vergano Miho Adachi-Fukuda Yasemin Alanay Adila AlKindy Anwar Baban Allan Bayat Stefanie Beck-Wödl Katherine Berry Emilia K Bijlsma Levinus A Bok Alwin F J Brouwer Ineke van der Burgt Philippe M Campeau Natalie Canham Krystyna Chrzanowska Yoyo W Y Chu Brain H Y Chung Karin Dahan Marjan De Rademaeker Anne Destree Tracy Dudding-Byth Rachel Earl Nursel Elcioglu Ellen R Elias Christina Fagerberg Alice Gardham Blanca Gener Erica H Gerkes Ute Grasshoff Arie van Haeringen Karin R Heitink Johanna C Herkert Nicolette S den Hollander Denise Horn David Hunt Sarina G Kant Mitsuhiro Kato Hülya Kayserili Rogier Kersseboom Esra Kilic Malgorzata Krajewska-Walasek Kylin Lammers Lone W Laulund Damien Lederer Melissa Lees Vanesa López-González Saskia Maas Grazia M S Mancini Carlo Marcelis Francisco Martinez Isabelle Maystadt Marianne McGuire Shane McKee Sarju Mehta Kay Metcalfe Jeff Milunsky Seiji Mizuno John B Moeschler Christian Netzer Charlotte W Ockeloen Barbara Oehl-Jaschkowitz Nobuhiko Okamoto Sharon N M Olminkhof Carmen Orellana Laurent Pasquier Caroline Pottinger Vera Riehmer Stephen P Robertson Maian Roifman Caroline Rooryck Fabienne G Ropers Monica Rosello Claudia A L Ruivenkamp Mahmut S Sagiroglu Suzanne C E H Sallevelt Amparo Sanchis Calvo Pelin O Simsek-Kiper Gabriela Soares Lucia Solaeche Fatma Mujgan Sonmez Miranda Splitt Duco Steenbeek Alexander P A Stegmann Constance T R M Stumpel Saori Tanabe Eyyup Uctepe G Eda Utine Hermine E Veenstra-Knol Sunita Venkateswaran Catheline Vilain Catherine Vincent-Delorme Anneke T Vulto-van Silfhout Patricia Wheeler Golder N Wilson Louise C Wilson Bernd Wollnik Tomoki Kosho Dagmar Wieczorek Evan Eichler Rolph Pfundt Bert B A de Vries Jill Clayton-Smith Gijs W E Santen

Genet Med 2019 Jan 29. Epub 2019 Jan 29.

Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.

The original version of this Article contained an error in the spelling of the author Pleuntje J. van der Sluijs, which was incorrectly given as Eline (P. J. Read More

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http://dx.doi.org/10.1038/s41436-018-0368-yDOI Listing
January 2019
3 Reads
7.329 Impact Factor

Best practice guidelines regarding diagnosis and management of patients with type II collagen disorders.

Genet Med 2019 Jan 30. Epub 2019 Jan 30.

Department of Orthopedics and Sports Medicine, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.

Purpose: Skeletal dysplasias comprise a heterogeneous group of inherited disorders of development, growth, and maintenance of the human skeleton. Because of their relative rarity and wide phenotypic variability, patients should be accurately identified, uniformly assessed, and managed by clinicians who are aware of their potential complications and possess the knowledge and resources to treat them effectively. This study presents expert guidelines developed to improve the diagnosis and management of patients with type II collagen skeletal disorders to optimize clinical outcomes. Read More

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http://dx.doi.org/10.1038/s41436-019-0446-9DOI Listing
January 2019

Current conditions in medical genetics practice.

Genet Med 2019 Jan 28. Epub 2019 Jan 28.

American College of Medical Genetics and Genomics, Bethesda, MD, USA.

Purpose: This study of current conditions in medical genetics practice is designed to inform public policy development and present possible solutions for improving access to genetic services.

Methods: Using the American College of Medical Genetics and Genomics Member Directory, membership directories from regional collaborative partners, listservs from national partners, and social media, a 16-question survey was electronically distributed in 2015.

Results: The responses of 924 genetics professionals and related providers present a snapshot of current practice and an assessment of workforce needs. Read More

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http://dx.doi.org/10.1038/s41436-018-0417-6DOI Listing
January 2019

Pathogenic variants in USP7 cause a neurodevelopmental disorder with speech delays, altered behavior, and neurologic anomalies.

Genet Med 2019 Jan 25. Epub 2019 Jan 25.

Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX, USA.

Purpose: Haploinsufficiency of USP7, located at chromosome 16p13.2, has recently been reported in seven individuals with neurodevelopmental phenotypes, including developmental delay/intellectual disability (DD/ID), autism spectrum disorder (ASD), seizures, and hypogonadism. Further, USP7 was identified to critically incorporate into the MAGEL2-USP7-TRIM27 (MUST), such that pathogenic variants in USP7 lead to altered endosomal F-actin polymerization and dysregulated protein recycling. Read More

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http://www.nature.com/articles/s41436-019-0433-1
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http://dx.doi.org/10.1038/s41436-019-0433-1DOI Listing
January 2019
3 Reads

Xrare: a machine learning method jointly modeling phenotypes and genetic evidence for rare disease diagnosis.

Genet Med 2019 Jan 24. Epub 2019 Jan 24.

Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.

Purpose: Despite the successful progress next-generation sequencing technologies has achieved in diagnosing the genetic cause of rare Mendelian diseases, the current diagnostic rate is still far from satisfactory because of heterogeneity, imprecision, and noise in disease phenotype descriptions and insufficient utilization of expert knowledge in clinical genetics. To overcome these difficulties, we present a novel method called Xrare for the prioritization of causative gene variants in rare disease diagnosis.

Methods: We propose a new phenotype similarity scoring method called Emission-Reception Information Content (ERIC), which is highly tolerant of noise and imprecision in clinical phenotypes. Read More

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http://www.nature.com/articles/s41436-019-0439-8
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http://dx.doi.org/10.1038/s41436-019-0439-8DOI Listing
January 2019
7 Reads

Next-generation sequencing of 32 genes associated with hereditary aortopathies and related disorders of connective tissue in a cohort of 199 patients.

Genet Med 2019 Jan 24. Epub 2019 Jan 24.

Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Purpose: Heritable factors play an important etiologic role in connective tissue disorders (CTD) with vascular involvement, and a genetic diagnosis is getting increasingly important for gene-tailored, personalized patient management.

Methods: We analyzed 32 disease-associated genes by using targeted next-generation sequencing and exome sequencing in a clinically relevant cohort of 199 individuals. We classified and refined sequence variants according to their likelihood for pathogenicity. Read More

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http://www.nature.com/articles/s41436-019-0435-z
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http://dx.doi.org/10.1038/s41436-019-0435-zDOI Listing
January 2019
3 Reads

ABCA4-associated disease as a model for missing heritability in autosomal recessive disorders: novel noncoding splice, cis-regulatory, structural, and recurrent hypomorphic variants.

Genet Med 2019 Jan 23. Epub 2019 Jan 23.

Center for Medical Genetics Ghent, Ghent University and Ghent University Hospital, Ghent, Belgium.

Purpose: ABCA4-associated disease, a recessive retinal dystrophy, is hallmarked by a large proportion of patients with only one pathogenic ABCA4 variant, suggestive for missing heritability.

Methods: By locus-specific analysis of ABCA4, combined with extensive functional studies, we aimed to unravel the missing alleles in a cohort of 67 patients (p), with one (p = 64) or no (p = 3) identified coding pathogenic variants of ABCA4.

Results: We identified eight pathogenic (deep-)intronic ABCA4 splice variants, of which five are novel and six structural variants, four of which are novel, including two duplications. Read More

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http://dx.doi.org/10.1038/s41436-018-0420-yDOI Listing
January 2019

Untargeted metabolomic profiling reveals multiple pathway perturbations and new clinical biomarkers in urea cycle disorders.

Genet Med 2019 Jan 23. Epub 2019 Jan 23.

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

Purpose: Untargeted metabolomic analysis is increasingly being used in the screening and management of individuals with inborn errors of metabolism (IEM). We aimed to test whether untargeted metabolomic analysis in plasma might be useful for monitoring the disease course and management of urea cycle disorders (UCDs).

Methods: Untargeted mass spectrometry-based metabolomic analysis was used to generate z-scores for more than 900 metabolites in plasma from 48 individuals with various UCDs. Read More

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http://dx.doi.org/10.1038/s41436-019-0442-0DOI Listing
January 2019

CYP2D6-guided opioid therapy improves pain control in CYP2D6 intermediate and poor metabolizers: a pragmatic clinical trial.

Genet Med 2019 Jan 23. Epub 2019 Jan 23.

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

Purpose: CYP2D6 bioactivates codeine and tramadol, with intermediate and poor metabolizers (IMs and PMs) expected to have impaired analgesia. This pragmatic proof-of-concept trial tested the effects of CYP2D6-guided opioid prescribing on pain control.

Methods: Participants with chronic pain (94% on an opioid) from seven clinics were enrolled into CYP2D6-guided (n = 235) or usual care (n = 135) arms using a cluster design. Read More

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http://www.nature.com/articles/s41436-018-0431-8
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January 2019
12 Reads

Response to Juang et al.

Genet Med 2019 Jan 22. Epub 2019 Jan 22.

Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.

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http://www.nature.com/articles/s41436-019-0437-x
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January 2019
3 Reads

Constructing identities: the implications of DTC ancestry testing for tribal communities.

Genet Med 2019 Jan 21. Epub 2019 Jan 21.

Department of Bioethics, Clinical Center, National Institutes of Health, Bethesda, MD, USA.

Purpose: Direct-to-consumer (DTC) genetic ancestry companies have rapidly increased in popularity, with top testing services maintaining genetic databases of several million consumers. While genetic ancestry tests are often characterized as recreational, companies invoke deeply personal concepts of individual identity, group membership, and kinship when marketing their services. In particular, many companies claim to be able to determine Native American heritage, claims that are not supported by the state of the science and may have significant cultural and political consequences for US tribal communities. Read More

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http://www.nature.com/articles/s41436-018-0429-2
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http://dx.doi.org/10.1038/s41436-018-0429-2DOI Listing
January 2019
3 Reads

Diagnosis and management of glycogen storage diseases type VI and IX: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).

Genet Med 2019 Jan 19. Epub 2019 Jan 19.

American College of Medical Genetics and Genomics, Bethesda, MD, USA.

Purpose: Glycogen storage disease (GSD) types VI and IX are rare diseases of variable clinical severity affecting primarily the liver. GSD VI is caused by deficient activity of hepatic glycogen phosphorylase, an enzyme encoded by the PYGL gene. GSD IX is caused by deficient activity of phosphorylase kinase (PhK), the enzyme subunits of which are encoded by various genes: ɑ (PHKA1, PHKA2), β (PHKB), ɣ (PHKG1, PHKG2), and δ (CALM1, CALM2, CALM3). Read More

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http://dx.doi.org/10.1038/s41436-018-0364-2DOI Listing
January 2019
9 Reads

Insights into genetics, human biology and disease gleaned from family based genomic studies.

Genet Med 2019 Jan 18. Epub 2019 Jan 18.

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

Identifying genes and variants contributing to rare disease phenotypes and Mendelian conditions informs biology and medicine, yet potential phenotypic consequences for variation of >75% of the ~20,000 annotated genes in the human genome are lacking. Technical advances to assess rare variation genome-wide, particularly exome sequencing (ES), enabled establishment in the United States of the National Institutes of Health (NIH)-supported Centers for Mendelian Genomics (CMGs) and have facilitated collaborative studies resulting in novel "disease gene" discoveries. Pedigree-based genomic studies and rare variant analyses in families with suspected Mendelian conditions have led to the elucidation of hundreds of novel disease genes and highlighted the impact of de novo mutational events, somatic variation underlying nononcologic traits, incompletely penetrant alleles, phenotypes with high locus heterogeneity, and multilocus pathogenic variation. Read More

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http://www.nature.com/articles/s41436-018-0408-7
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January 2019
13 Reads

Correction: A new microdeletion syndrome involving TBC1D24, ATP6V0C, and PDPK1 causes epilepsy, microcephaly, and developmental delay.

Genet Med 2019 Jan 14. Epub 2019 Jan 14.

Department of Pediatrics, Université de Montréal, Montreal, QC, Canada.

The original version of this Article contained an error in the spelling of the author Siddharth Banka, which was incorrectly given as Siddhart Banka. This has now been corrected in both the PDF and HTML versions of the Article. Read More

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http://www.nature.com/articles/s41436-018-0413-x
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http://dx.doi.org/10.1038/s41436-018-0413-xDOI Listing
January 2019
6 Reads
7.329 Impact Factor

Deep-intronic ABCA4 variants explain missing heritability in Stargardt disease and allow correction of splice defects by antisense oligonucleotides.

Genet Med 2019 Jan 15. Epub 2019 Jan 15.

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

Purpose: Using exome sequencing, the underlying variants in many persons with autosomal recessive diseases remain undetected. We explored autosomal recessive Stargardt disease (STGD1) as a model to identify the missing heritability.

Methods: Sequencing of ABCA4 was performed in 8 STGD1 cases with one variant and p. Read More

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http://dx.doi.org/10.1038/s41436-018-0414-9DOI Listing
January 2019
2 Reads

Revising the Psychiatric Phenotype of Homocystinuria.

Genet Med 2019 Jan 15. Epub 2019 Jan 15.

Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Purpose: Associations of psychiatric and psychological symptoms with homocystinuria (HCU) have been described in multiple reports. This retrospective study was undertaken to refine the psychological phenotype among HCU patients and identify biomedical markers that could be used for prediction of those psychiatric or psychological symptoms.

Methods: This study examines the prevalence of psychological symptoms within a sample of 25 patients with classical homocystinuria. Read More

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http://www.nature.com/articles/s41436-018-0419-4
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http://dx.doi.org/10.1038/s41436-018-0419-4DOI Listing
January 2019
3 Reads

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

Genet Med 2019 Jan 15. Epub 2019 Jan 15.

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

Purpose: Breast cancer (BC) risk prediction allows systematic identification of individuals at highest and lowest risk. We extend the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk model to incorporate the effects of polygenic risk scores (PRS) and other risk factors (RFs).

Methods: BOADICEA incorporates the effects of truncating variants in BRCA1, BRCA2, PALB2, CHEK2, and ATM; a PRS based on 313 single-nucleotide polymorphisms (SNPs) explaining 20% of BC polygenic variance; a residual polygenic component accounting for other genetic/familial effects; known lifestyle/hormonal/reproductive RFs; and mammographic density, while allowing for missing information. Read More

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http://dx.doi.org/10.1038/s41436-018-0406-9DOI Listing
January 2019
1 Read

TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model.

Genet Med 2019 Jan 14. Epub 2019 Jan 14.

Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Purpose: To characterize clinically measurable endophenotypes, implicating the TBX6 compound inheritance model.

Methods: Patients with congenital scoliosis (CS) from China(N = 345, cohort 1), Japan (N = 142, cohort 2), and the United States (N = 10, cohort 3) were studied. Clinically measurable endophenotypes were compared according to the TBX6 genotypes. Read More

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http://www.nature.com/articles/s41436-018-0377-x
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January 2019
7 Reads
7.329 Impact Factor

Response to Gammal et al.

Genet Med 2019 Jan 11. Epub 2019 Jan 11.

Pharmacogenomics Analysis Laboratory, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.

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http://www.nature.com/articles/s41436-018-0422-9
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http://dx.doi.org/10.1038/s41436-018-0422-9DOI Listing
January 2019
1 Read

The illusion of polygenic disease risk prediction.

Genet Med 2019 Jan 12. Epub 2019 Jan 12.

Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, UK.

A problem at the interface of genomic medicine and medical screening is that genetic associations of etiological significance are often interpreted as having predictive significance. Genome-wide association studies (GWAS) have identified many thousands of associations between common DNA variants and hundreds of diseases and benign traits. This knowledge has generated many publications with the understandable expectation that it can be used to derive polygenic risk scores for predicting disease to identify those at sufficiently high risk to benefit from preventive intervention. Read More

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http://dx.doi.org/10.1038/s41436-018-0418-5DOI Listing
January 2019

Transcription alterations of KCNQ1 associated with imprinted methylation defects in the Beckwith-Wiedemann locus.

Genet Med 2019 Jan 12. Epub 2019 Jan 12.

Dipartimento di Scienze e Tecnologie Ambientali, Biologiche e Farmaceutiche, Università della Campania "Luigi Vanvitelli", Caserta, Italy.

Purpose: Beckwith-Wiedemann syndrome (BWS) is a developmental disorder caused by dysregulation of the imprinted gene cluster of chromosome 11p15.5 and often associated with loss of methylation (LOM) of the imprinting center 2 (IC2) located in KCNQ1 intron 10. To unravel the etiological mechanisms underlying these epimutations, we searched for genetic variants associated with IC2 LOM. Read More

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http://www.nature.com/articles/s41436-018-0416-7
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http://dx.doi.org/10.1038/s41436-018-0416-7DOI Listing
January 2019
5 Reads

Considerations for pharmacogenomic testing in a health system.

Genet Med 2019 Jan 9. Epub 2019 Jan 9.

Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.

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http://www.nature.com/articles/s41436-018-0421-x
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http://dx.doi.org/10.1038/s41436-018-0421-xDOI Listing
January 2019
3 Reads

Are women with pathogenic variants in PMS2 and MSH6 really at high lifetime risk of breast cancer?

Genet Med 2018 Dec 14. Epub 2018 Dec 14.

Hereditary Cancer Program, Institut Catal. d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.

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http://www.nature.com/articles/s41436-018-0401-1
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http://dx.doi.org/10.1038/s41436-018-0401-1DOI Listing
December 2018
1 Read

Phenylalanine and tyrosine measurements across gestation by tandem mass spectrometer on dried blood spot cards from normal pregnant women.

Genet Med 2019 Jan 10. Epub 2019 Jan 10.

Division of Genetic and Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, 43205, USA.

Purpose: Maternal phenylketonuria (MPKU) requires strict control of phenylalanine (Phe) and supplemental tyrosine (Tyr). Monitoring during pregnancy using dried blood spot (DBS) cards by tandem mass spectrometry (MS/MS) is now standard practice, however there are no Phe and Tyr reference ranges for DBS MS/MS method in healthy pregnant women.

Methods: DBS cards (63-1364 days in storage) from healthy women with singleton pregnancies were analyzed by MS/MS. Read More

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http://dx.doi.org/10.1038/s41436-018-0407-8DOI Listing
January 2019

Correction: Biallelic sequence and structural variants in RAX2 are a novel cause for autosomal recessive inherited retinal disease.

Genet Med 2019 Jan 3. Epub 2019 Jan 3.

Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.

The original version of this Article contained an incorrect version of Fig. 3, which included two variants initially shown in black text in Fig. 3a that the authors removed from the final manuscript. Read More

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http://www.nature.com/articles/s41436-018-0392-y
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http://dx.doi.org/10.1038/s41436-018-0392-yDOI Listing
January 2019
6 Reads

Loss of function of SVBP leads to autosomal recessive intellectual disability, microcephaly, ataxia, and hypotonia.

Genet Med 2019 Jan 4. Epub 2019 Jan 4.

Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Purpose: Identifying and characterizing novel causes of autosomal recessive intellectual disability based on systematic clinical and genetic evaluation, followed by functional experiments.

Methods: Clinical examinations, genome-wide positional mapping, and sequencing were followed by quantitative polymerase chain reaction and western blot of the protein SVBP and its interaction partners. We then knocked down the gene in rat primary hippocampal neurons and evaluated the consequences on synapses. Read More

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http://dx.doi.org/10.1038/s41436-018-0415-8DOI Listing
January 2019
2 Reads
7.329 Impact Factor

A CRISPR focus on attitudes and beliefs toward somatic genome editing from stakeholders within the sickle cell disease community.

Genet Med 2018 Dec 24. Epub 2018 Dec 24.

Social and Behavioral Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.

Purpose: Genome editing holds both tremendous therapeutic promise and significant potential risk. Sickle cell disease (SCD), the most commonly inherited blood disorder, is a frontline candidate for the clinical applications of this tool. However, there is limited knowledge of patient community values and concerns regarding this new technology. Read More

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http://www.nature.com/articles/s41436-018-0409-6
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http://dx.doi.org/10.1038/s41436-018-0409-6DOI Listing
December 2018
10 Reads

Patient re-contact after revision of genomic test results: points to consider-a statement of the American College of Medical Genetics and Genomics (ACMG).

Genet Med 2018 Dec 22. Epub 2018 Dec 22.

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

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http://dx.doi.org/10.1038/s41436-018-0391-zDOI Listing
December 2018
1 Read

Cancer communication research in the era of genomics and precision medicine: a scoping review.

Genet Med 2018 Dec 21. Epub 2018 Dec 21.

National Cancer Institute, Bethesda, MD, USA.

Effective use of genetic and genomic data in cancer prevention and treatment depends on adequate communication with patients and the public. Although relevant empirical work has emerged, the scope and outcomes of this communication research have not been characterized. We conducted a comprehensive scoping review of recent published research (2010-2017) on communication of cancer-related genetic and genomic testing (CGT) information. Read More

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http://dx.doi.org/10.1038/s41436-018-0402-0DOI Listing
December 2018
1 Read

Biallelic germline nonsense variant of MLH3 underlies polyposis predisposition.

Genet Med 2018 Dec 21. Epub 2018 Dec 21.

Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki, Finland.

Purpose: Some 10% of familial adenomatous polyposis (FAP) and 80% of attenuated polyposis (AFAP) cases remain molecularly unexplained. We scrutinized such cases by exome-wide and targeted methods to search for novel susceptibility genes.

Methods: Exome sequencing was conducted on 40 unexplained (mainly sporadic) cases with FAP or AFAP from Finland. Read More

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http://www.nature.com/articles/s41436-018-0405-x
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http://dx.doi.org/10.1038/s41436-018-0405-xDOI Listing
December 2018
41 Reads

Marfan syndrome: improved clinical history results in expanded natural history.

Authors:
Reed E Pyeritz

Genet Med 2018 Dec 21. Epub 2018 Dec 21.

Departments of Medicine and Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Life expectancy for a person with Marfan syndrome has essentially doubled over the past four decades. During this period, the clinical histories of the organs managed routinely have improved, and will continue to be. Prominent examples are the eyes, the heart and aorta, and some features of the skeletal system. Read More

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http://dx.doi.org/10.1038/s41436-018-0399-4DOI Listing
December 2018

45,X mosaicism in a population-based biobank: implications for Turner syndrome.

Genet Med 2018 Dec 21. Epub 2018 Dec 21.

Medical Genetics Unit, Department of Pediatrics, MassGeneral Hospital for Children, Boston, MA, USA.

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http://www.nature.com/articles/s41436-018-0411-z
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http://dx.doi.org/10.1038/s41436-018-0411-zDOI Listing
December 2018
13 Reads

Next-generation phenotyping using computer vision algorithms in rare genomic neurodevelopmental disorders.

Genet Med 2018 Dec 20. Epub 2018 Dec 20.

Princess Máxima Center for Pediatric Oncology, Bilthoven, The Netherlands.

Purpose: The interpretation of genetic variants after genome-wide analysis is complex in heterogeneous disorders such as intellectual disability (ID). We investigate whether algorithms can be used to detect if a facial gestalt is present for three novel ID syndromes and if these techniques can help interpret variants of uncertain significance.

Methods: Facial features were extracted from photos of ID patients harboring a pathogenic variant in three novel ID genes (PACS1, PPM1D, and PHIP) using algorithms that model human facial dysmorphism, and facial recognition. Read More

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http://dx.doi.org/10.1038/s41436-018-0404-yDOI Listing
December 2018