Genetics in Medicine

Article	Citations
Table of Contents	469
Desperately seeking solutions	407
Where there is no genetic counselor: An online decision-aid supports the majority of parents’ diagnostic genomic testing choices for their children	375
Educational considerations based on medical student use of polygenic risk information and apparent race in a simulated consultation	230
Expanding the phenotype and genotype spectrum of TAOK1 neurodevelopmental disorder and delineating TAOK2 neurodevelopmental disorder	201
Editorial Board	196
Editorial Board	182
Table of Contents	140
Systematic evidence-based review: The application of noninvasive prenatal screening using cell-free DNA in general-risk pregnancies	131
Editorial Board	125
eP234: SERPINA1 sequencing facilitates detection of undiagnosed Alpha-1 antitrypsin deficiency	114
eP256: Intrafamilial variability in chromosome 2q13 microdeletion: Case report and review of the literature	105
eP169: A case report of Ververi-Brady syndrome: Expanding the genotype and phenotype	105
eP162: Mosaic variant in ENG in infant with pulmonary arteriovenous malformations: Case report and review of hereditary hemorrhagic telangiectasia	104
eP498: Detection of congenital cytomegalovirus infection on high-risk newborn population	97
OP037: Assessing the impact of expanded ACMG secondary findings recommendations on population genomic screening in the Geisinger MyCode Community Health Initiative	94
eP033: COASY-associated pontocerebellar hypoplasia – A possible additional secondary target detectable by expanded newborn screening?	93
eP049: Discordant fluorescence in situ hybridization and RNASeq results in the identification of fusion partners in recurring translocations in hematological malignancies	77
eP179: Expanding the phenotype of CLCN6-associated early-onset neurodegeneration	72
eP290: A mosaic Angelman syndrome case with language apraxia and symptoms overlapping Prader-Willi syndrome	71
OP055: Comparing error rates in disclosure of genome sequencing results between non-genetics providers and genetic counselors	68
Paired-like homeobox gene (PHOX2B) nonpolyalanine repeat expansion mutations (NPARMs): genotype–phenotype correlation in congenital central hypoventilation syndrome (CCHS)	68
Cascade testing after exome sequencing: Retrospective analysis of linked family data at 2 US laboratories	67
Increasing inclusivity in precision medicine research: Views of deaf and hard of hearing individuals	66
Biallelic DAW1 variants cause a motile ciliopathy characterized by laterality defects and subtle ciliary beating abnormalities	63

Biallelic PRMT7 pathogenic variants are associated with a recognizable syndromic neurodevelopmental disorder with short stature, obesity, and craniofacial and digital abnormalities	62
Functional genomics for curation of variants in telomere biology disorder associated genes: A systematic review	61
Scoping review and classification of deep learning in medical genetics	60
From genes to public health: are we ready for DNA-based population screening?	60
Optical genome mapping improves clinical interpretation of constitutional copy number gains and reduces their VUS burden	60
The effect of early hormonal treatment (EHT) on expressive and receptive language capabilities in boys with 47,XXY (Klinefelter syndrome) during infancy and early childhood	60
Elucidating the clinical spectrum and molecular basis of HYAL2 deficiency	59
Correspondence on “Genomic insights from a deeply phenotyped highly consanguineous neurodevelopmental disorders cohort” by Akter et al	56
ClinGen recuration of hearing loss-associated genes demonstrates significant changes in gene-disease validity over time	56
Estimation of carrier frequencies of autosomal and X-linked recessive genetic conditions based on gnomAD v4.0 data in different ancestries	56
Inherited variants in CHD3 show variable expressivity in Snijders Blok-Campeau syndrome	54
Clinical likelihood ratios and balanced accuracy for 44 in silico tools against multiple large-scale functional assays of cancer susceptibility genes	52
The importance of automation in genetic diagnosis: Lessons from analyzing an inherited retinal degeneration cohort with the Mendelian Analysis Toolkit (MATK)	52
Cost-effectiveness of exome and genome sequencing for children with rare and undiagnosed conditions	51
The clinical geneticist workforce: Community forums to address challenges and opportunities	48
eP114: De novo prenatal diagnosis of X-linked Acromegaly Gigantism (X-LAG)	48
Improving racial diversity in the genomics workforce: An examination of challenges and opportunities	48
eP229: A case report of a complex chromosome 8 rearrangement with partial monosomy of 8p and partial trisomy of 8q	47
eP263: A pathogenic deletion at 13q32.1q33.1 presenting with bilateral sensorineural hearing loss and pigmentation anomalies, mimicking Waardenburg syndrome	47
eP358: Genetic findings in a cohort of patients with pulmonary arterial hypertension referred for NGS panel testing	46
eP509: Implementation and impact of dedicated inpatient genetic counselors in a children’s hospital	46
News	45
eP512: Identifying clinical and psychological factors associated with genomics-related outcomes in a centralized sequencing protocol	45
Editorial Board	45
CFTR genotype analysis of Asians in international registries highlights disparities in the diagnosis and treatment of Asian patients with cystic fibrosis	44
Calibrating variant curation by clinical context based on factors that influence patients’ tolerance of uncertainty	44
De novo variants are a common cause of genetic hearing loss	44
Characterization of central manifestations in patients with Niemann-Pick disease type C	43
Long-term effects of eliglustat on skeletal manifestations in clinical trials of patients with Gaucher disease type 1	43
“The truth should not be hidden”: Experiences and recommendations of individuals making NPE discoveries through genetic genealogy databases	42
Universal tumor screening in a population with MSH6- and PMS2-associated Lynch syndrome	42
OP048: The impact of route of delivery on surgical morbidity in fetuses affected by achondroplasia: A multicenter retrospective study	41
A novel DPH5-related diphthamide-deficiency syndrome causing embryonic lethality or profound neurodevelopmental disorder	41
Clinical implementation of genetic testing in adults for hereditary hematologic malignancy syndromes	41
Challenges for precision public health communication in the era of genomic medicine	41
eP462: Detection of clinically relevant exonic copy number changes in fetuses by chromosomal microarray analysis	40
eP018: Late-onset congenital erythropoietic porphyria associated with myeloid malignancy	40
eP321: Extending and adapting the functions of genetic laboratories in the continuing COVID pandemic–challenges and successes	40
eP073: Interstitial deletion of 3q21 in a child with multiple congenital anomalies; Expanding the phenotype	40
eP244: Rapid exome sequencing influences acute and long-term management of critically unwell children and their families	39
eP270: Incorporating genetic services into adult kidney disease care	39
eP088: Diagnosing a patient with progressive myoclonic epilepsy-12 with variants of uncertain significance on exome sequencing	39
eP005: Complex glycerol kinase deficiency and X-linked intellectual disability	38
eP354: A systematic approach for applying disease-specific phenotype in clinical variant interpretation	36
The splicing effect of variants at branchpoint elements in cancer genes	36
Masthead	35
Correspondence on “Genotypic and phenotypic spectrum of infantile liver failure due to pathogenic TRMU variants” by Vogel et al	35
Refining the risk for fragile X–associated primary ovarian insufficiency (FXPOI) by FMR1 CGG repeat size	34
Real-world diagnostic outcomes and cost-effectiveness of genome-wide sequencing for developmental and seizure disorders: Evidence from Canada	34
Biallelic CRELD1 variants cause a multisystem syndrome, including neurodevelopmental phenotypes, cardiac dysrhythmias, and frequent infections	34

Exploring Autistic adults’ perspectives on genetic testing for autism	33
Expanding SPTAN1 monoallelic variant associated disorders: From epileptic encephalopathy to pure spastic paraplegia and ataxia	33
Reproductive outcomes in individuals with chromosomal reciprocal translocations	33
Next-generation sequencing for constitutional variants in the clinical laboratory, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG)	33
Diagnosing, discarding, or de-VUSsing: A practical guide to (un)targeted metabolomics as variant-transcending functional tests	32
Updated clinical practice recommendations for managing adults with 22q11.2 deletion syndrome	32
Correspondence on “Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: A practice resource of the American College of Medical Genetics and Genomics (ACMG)” by	32
1-13C-propionate breath testing as a surrogate endpoint to assess efficacy of liver-directed therapies in methylmalonic acidemia (MMA)	32
Documentation of results and medication prescribing after combinatorial psychiatric pharmacogenetic testing: A case for discrete results	32
Genetics providers’ perspectives on the use of digital tools in clinical practice	32
Impact of genetic counseling strategy on diagnostic yield and workload for genome-sequencing-based tumor diagnostics	31
COVID-19 in people with neurofibromatosis 1, neurofibromatosis 2, or schwannomatosis	31
Pregnant Latinas’ views of adopting exome sequencing into newborn screening: A qualitative study	31
Correspondence on “Comparison of literature mining tools for variant classification: Through the lens of 50 RYR1 variants” by Wermers et al	30
Response to Shen et al.	30
Improved detection of mitochondrial DNA instability in mitochondrial genome maintenance disorders	30
Pubertal growth in osteogenesis imperfecta caused by pathogenic variants in COL1A1/COL1A2	30
Couple-based expanded carrier screening provided by general practitioners to couples in the Dutch general population: psychological outcomes and reproductive intentions	30
Novel insights into the phenotypic spectrum and pathogenesis of Hardikar syndrome	29
Response to Kiel and Kozaric	29
Masthead	29
Response to Stern	28
eP398: Searching beyond the exons in nuclear genes: Diagnostic deep intronic and mitochondrial variants in patients with monogenic diabetes	28
eP446: High rates of ‘atypical’ panorama noninvasive prenatal screening results among consanguineous Arab American women	28
eP082: Associated recessive retinitis pigmentosa caused by paternal uniparental disomy	28
Editorial Board	28
Biallelic variation in the choline and ethanolamine transporter FLVCR1 underlies a severe developmental disorder spectrum	28
eP342: Clinical testing of SHOX gene for SHOX deficiency disorders	28
eP006: Homocystinuria in an adolescent patient with Chr21q22.2q22.3 deletion	27
eP198: EIF3F compound heterozygous genotype-phenotype association	27
eP153: WASF2 variants contribute to heart failure phenotypes	27
eP091: Improving cytogenetic testing utilization in a tertiary care NICU through quality improvement	27
eP249: Practical implementation of inpatient rapid comprehensive sequencing for critically ill pediatric patients	27
eP364: Lessons from pathogenicity classifications for 251 RYR1 variants associated with malignant hyperthermia susceptibility using variant curation expert panel revised criteria	27
Systematic assessment of outcomes following a genetic diagnosis identified through a large-scale research study into developmental disorders	26
Secondary ACMG and non-ACMG genetic findings in a multiethnic cohort of 16,713 pediatric participants	26
OP012: Perceptions of breast and ovarian cancer risk and genetic testing among Non-Hispanic Black women	26
Evaluating the return of additional findings from the 100,000 Genomes Project: A mixed methods study exploring participant experiences of receiving secondary findings from genomic sequencing	26
Frequency of epistaxis and telangiectasia in patients with hereditary hemorrhagic telangiectasia (HHT) in comparison with the general population: Curaçao diagnostic criteria revisited	26
InpherNet accelerates monogenic disease diagnosis using patients’ candidate genes’ neighbors	26
Noncoding variants are a rare cause of recessive developmental disorders in trans with coding variants	26
Neurofilament light chain in cerebrospinal fluid as a novel biomarker in evaluating both clinical severity and therapeutic response in Niemann-Pick disease type C1	25
Genome sequencing detects a wide range of clinically relevant copy-number variants and other genomic alterations	25
The ACMG SF v3.0 gene list increases returnable variant detection by 22% when compared with v2.0 in the ClinSeq cohort	25
Rethinking Agency for Genetic Testing Intention among Latinos: Determining Predictors of Intention for Carrier Screening and Cancer Predisposition Testing	25
Laboratory business models and practices: implications for availability and access to germline genetic testing	25
The Parent PrU: A measure to assess personal utility of pediatric genomic results	24
Clinical spectrum of MTOR-related hypomelanosis of Ito with neurodevelopmental abnormalities	24
Awareness and use of genetic testing: An analysis of the Health Information National Trends Survey 2020	24
Expanding the genetics and phenotypes of ocular congenital cranial dysinnervation disorders	24
The opinions and experiences of people with intellectual disability regarding genetic testing and genetic medicine: A systematic review	24
Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders	24
Risk of cancer in heterozygous relatives of patients with Fanconi anemia	23
eP405: Clinical application of 24-hour ultra-rapid genome sequencing in a critically ill neonate	23
eP328: Establishing droplet digital PCR method for assessing mitochondrial DNA content in muscle	23
Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire	23
eP040: Breast cancer patients categorized as high-risk of recurrence and/or basal-type molecular subtype by Agendia should universally undergo germline genetic testing	23
eP052: Coding defects in chromosomal segregation and protein targeting are central to TGCT predisposition	23
ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG)	23
eP128: A novel CSNK1E variant in a patient with autism spectrum disorder	23
eP164: A case report of neurological manifestations and failure to thrive in neurobehavioural disease caused by a variant in RFX7	23
OP019: A tertiary care clinical sequencing program for patients with suspected immune defects: Results from the first 1000 families	22
eP094: Diagnostic yield of chromosomal microarray in congenital heart disease: A single center retrospective study	22
Novel loss-of-function variant in DENND5A impedes melanosomal cargo transport and predisposes to familial cutaneous melanoma	22
OP059: Clinical impact of a targeted pharmacogenomic assessment within a cohort of individuals with suspected inborn errors of immunity	22
Validation of the International Breast Cancer Intervention Study (IBIS) model in the High Risk Ontario Breast Screening Program: A retrospective cohort study	22
eP271: Bi-allelic loss of function variant of the ACTG2 gene that proposes a potential novel mechanism for visceral myopathies	22
eP391: Optical genome mapping for constitutional postnatal SV, CNV, and repeat array sizing: A multi-site clinical study	22
Editorial Board	22
Masthead	22
eP078: Phenotypes and genotypes in a cohort of children with single ventricle congenital heart disease	22
OP046: Stigma manifestations impact patient and clinical outcomes in cardiogenetic care: “Sometimes it’s depressing. Sometimes I feel like giving up.”	22
eP426: Utilization of the ACMG ACT sheets and algorithms on the ACMG website	22
Heterozygous UCHL1 loss-of-function variants cause a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy	22
Mapping the genetic landscape of treatable inherited metabolic disorders in a large Middle Eastern biobank	22
High-affinity FcγRIIIa genetic variants and potent NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) responses contributing to severe COVID-19	21
Optical genome mapping and revisiting short-read genome sequencing data reveal previously overlooked structural variants disrupting retinal disease−associated genes	21
eP384: Clinical, epidemiological and genetic characteristics of children diagnosed with Multisystem Inflammatory Syndrome (MIS-C) in Kuwait	21
Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies	21
High rate of hypomorphic variants as the cause of inherited ataxia and related diseases: study of a cohort of 366 families	21

Correspondence on “The evolving role of medical geneticists in the era of gene therapy: An urgency to prepare” by Vockley et al	21
Clinical and functional heterogeneity associated with the disruption of retinoic acid receptor beta	21
Focused Revision: Policy statement on folic acid and neural tube defects	21
Pancreatic cancer risk to siblings of probands in bilineal cancer settings	21
Privacy practices using genetic data from cell-free DNA aneuploidy screening	21
The 2019 medical genetics workforce: A focus on laboratory geneticists	21
ORCA, a values-based decision aid for selecting additional findings from genomic sequencing in adults: Efficacy results from a randomized trial	21
Automated reanalysis application to assist in detecting novel gene–disease associations after genome sequencing	20
Potential of polygenic risk scores for improving population estimates of women’s breast cancer genetic risks	20
The role of digital tools in the delivery of genomic medicine: enhancing patient-centered care	20
Editorial Board	20
Safety and efficacy of low-dose PI3K inhibitor taselisib in adult patients with CLOVES and Klippel–Trenaunay syndrome (KTS): the TOTEM trial, a phase 1/2 multicenter, open-label, single-arm study	20
Meta-analysis of the diagnostic and clinical utility of exome and genome sequencing in pediatric and adult patients with rare diseases across diverse populations	20
The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant	20
Validation of lung cancer polygenic risk scores in a high-risk case-control cohort	20
Editorial Board	20
Additional findings from the 100,000 Genomes Project: A qualitative study of recipient perspectives	20
Natural history of TANGO2 deficiency disorder: Baseline assessment of 73 patients	20
In This Issue	20
The impact of genetic counselor involvement in genetic and genomic test order review: A scoping review	20
eP208: GSD IX natural history and novel liver disease severity score: Multicenter international collaboration uncovers longitudinal trends in liver disease severity	19
eP248: Impact of DNA methylation signature exploration for variants of uncertain significance within epigenetic syndromes	19
Table of Contents	19
eP383: Mayo Clinic GeneGuide: A population-scale genetic interpretation software for reporting pathogenic and likely pathogenic variants impacting the CDC Tier1 genes	19
eP034: Novel use of global untargeted metabolomics in a patient with glycogen storage disease Ib receiving off label empagliflozin treatment	19
eP421: Development of an in-house whole transcriptome test for evaluation of splicing VUS variants: Experience and challenges in variant interpretation	19
Masthead	19
eP473: Patient attitudes and preferences about expanded noninvasive prenatal screening	19
eP265: Higher rates of non-skeletal complications in achondroplasia compared to the general population: A UK matched cohort study using CPRD-GOLD database	19
OP002: Secondary data analysis: Opportunities to advance genetic disease understanding and newborn screening research	19
Table of Contents	19
eP333: Tracking the emergence of SARS-CoV-2 variants of concern in vaccinated and unvaccinated patients	19
eP154: Predictive genomic medicine for thoracic aortic aneurysm and dissection	18
eP272: Familial pathogenic variant causing osteogenesis imperfecta identified in the Puerto Rican population	18
Fraud in genetic testing: Swindling the system	18
Correction to: The genetic architecture of Plakophilin 2 cardiomyopathy	18
OP040: Clinical validation of tagmentation-based genome sequencing for germline disorders	18
eP376: NGS detection of NUDT15 6-bp insertion and UGT1A1 (TA) repeat polymorphism on a preventative genomics assay	18
eP038: A new biochemical assay to measure plasmalogens with CLIR disease differentiation	18
Masthead	18
The Clinician-reported Genetic Testing Utility Index (C-GUIDE) for Prenatal Care: Initial evidence of content and construct validity	18
eP041: How long will they wait? Applying updated NCCN criteria to previously unqualified patients reveals missed opportunities for personalized cancer management	18
eP429: Factors associated with the time to complete clinical exome sequencing in a pediatric patient population	18
eP055: The Clinical Genome Resource (ClinGen) Somatic Cancer Clinical Domain Working Group	18
Germline variants in HEY2 functional domains lead to congenital heart defects and thoracic aortic aneurysms	18
PIGG variant pathogenicity assessment reveals characteristic features within 19 families	17
Genome-wide epigenetic signatures facilitated the variant classification of the PURA gene and uncovered the pathomechanism of PURA-related neurodevelopmental disorders	17
OP016: Mini-COMET: Safety and efficacy of ≥97 weeks’ avalglucosidase alfa in infantile-onset Pompe disease participants previously treated with alglucosidase alfa	17
Functional characteristics of a broad spectrum of TBX6 variants in Mayer-Rokitansky-Küster-Hauser syndrome	17
Improving care for rare genetic neurodevelopmental disorders: A systematic review and critical appraisal of clinical practice guidelines using AGREE II	17
Large scale clinical exome sequencing uncovers the scope and severity of skin disorders associated with MC1R genetic variants	17
“Doctors shouldn’t have to cheat the system”: Clinicians’ real-world experiences of the utility of genomic sequencing	17
The contribution of medical burden to 22q11.2 deletion syndrome quality of life and functioning	17
De novo PHF5A variants are associated with craniofacial abnormalities, developmental delay, and hypospadias	17
SOX11 variants cause a neurodevelopmental disorder with infrequent ocular malformations and hypogonadotropic hypogonadism and with distinct DNA methylation profile	17
Impact of integrated translational research on clinical exome sequencing	17
Response to Timothé Ménard	17
Cost-effectiveness of population-wide genomic screening for Lynch Syndrome and polygenic risk scores to inform colorectal cancer screening	17
Genetic testing in ambulatory cardiology clinics reveals high rate of findings with clinical management implications	17
Gene-specific ACMG/AMP classification criteria for germline APC variants: Recommendations from the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel	17
Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish	17
CIAO1 and MMS19 deficiency: A lethal neurodegenerative phenotype caused by cytosolic Fe-S cluster protein assembly disorders	17
Pathogenic variants in the paired-related homeobox 1 gene (PRRX1) cause craniosynostosis with incomplete penetrance	16
Classification of variants of reduced penetrance in high-penetrance cancer susceptibility genes: Framework for genetics clinicians and clinical scientists by CanVIG-UK (Cancer Variant Interpretation G	16
Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study	16
A systematic review of the methodological quality of economic evaluations in genetic screening and testing for monogenic disorders	16
Standardizing variation: Scaling up clinical genomics in Australia	16
Breast cancer polygenic risk scores: a 12-month prospective study of patient reported outcomes and risk management behavior	16
Clinical factors associated with genetic diagnosis in suspected neurogenetic disorders in a tertiary care clinic	16
Standards for the classification of pathogenicity of somatic variants in cancer (oncogenicity): Joint recommendations of Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC), and Varia	15
Mainstreaming of clinical genetic testing: a conceptual framework	15
Editorial Board	15
OP047: Timely diagnosis of mucopolysaccharidosis: Results from an innovative physician education program with a national outreach	15
eP108: PPP1CB-related Noonan syndrome with loose anagen hair presenting with focal cortical dysplasia and epilepsy	15
eP418: Enabling reclassification of missense variants in PKD1/2 – the power of a commercial laboratory database	15
Measurement of lysosomal enzyme activities: A technical standard of the American College of Medical Genetics and Genomics (ACMG)	15
A meta-analysis of diagnostic yield and clinical utility of genome and exome sequencing in pediatric rare and undiagnosed genetic diseases	15
Genomic testing for suspected monogenic kidney disease in children and adults: A health economic evaluation	15
eP125: Variants in obesity-related genes in a population with early-onset obesity	15
eP332: The importance of parental sequencing depth in the setting of rapid genome sequencing	15
eP520: Screening results in 186 any-health-status adults in primary care clinics receiving clinical NGS for 431 health risk and recessive genes	15
Economic evaluation of population-based, expanded reproductive carrier screening for genetic diseases in Australia	15
Genetic Determinants of Sudden Unexpected Death in Pediatrics	15
The mitochondrial seryl-tRNA synthetase SARS2 modifies onset in spastic paraplegia type 4	15
Table of Contents	15
eP341: The full (mutation) picture: One-third of patients with Fragile X syndrome present with neurodevelopmental disorders without dysmorphism or family history	15
eP330: Mosaicism for SMARCB1 or LZTR1 variants in patients with schwannomatosis in the UAB cohort	15
OP011: Physician recommendations after germline sequencing in pediatric cancer patients: Texas KidsCanSeq study	15
Inactivation of DRG1, encoding a translation factor GTPase, causes a recessive neurodevelopmental disorder	14
Biomarker testing for lysosomal diseases: A technical standard of the American College of Medical Genetics and Genomics (ACMG)	14
YWHAE loss of function causes a rare neurodevelopmental disease with brain abnormalities in human and mouse	14
In This Issue	14
Residual risk for additional recessive diseases in consanguineous couples	14
One is the loneliest number: genotypic matchmaking using the electronic health record	14
The difficulties of broad data sharing in genomic medicine: Empirical evidence from diverse participants in prenatal and pediatric clinical genomics research	14