Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72 400 specimens

Spinal muscular atrophy (SMA) is a leading inherited cause of infant death with a reported incidence of ∼1 in 10 000 live births and is second to cystic fibrosis as a common, life-shortening autosomal recessive disorder. The American College of Medical Genetics has recommended population carrier screening for SMA, regardless of race or ethnicity, to facilitate informed reproductive options, although other organizations have cited the need for additional large-scale studies before widespread implementation. We report our data from carrier testing (n=72 453) and prenatal diagnosis (n=121) for this condition. Our analysis of large-scale population carrier screening data (n=68 471) demonstrates the technical feasibility of high throughput testing and provides mutation carrier and allele frequencies at a level of accuracy afforded by large data sets. In our United States pan-ethnic population, the calculated a priori carrier frequency of SMA is 1/54 with a detection rate of 91.2%, and the pan-ethnic disease incidence is calculated to be 1/11 000. Carrier frequency and detection rates provided for six major ethnic groups in the United States range from 1/47 and 94.8% in the Caucasian population to 1/72 and 70.5% in the African American population, respectively. This collective experience can be utilized to facilitate accurate pre- and post-test counseling in the settings of carrier screening and prenatal diagnosis for SMA.

• Publication year

  2011

• Venue

  European Journal of Human Genetics

• Publication date

  2011-08-03

• Fields of study

  Medicine

• Identifiers
  DOI 10.1038/ejhg.2011.134PMID 21811307PMCID 3234503
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Population carrier screening for spinal muscular atrophy a position statement of the association for molecular pathology.

  2011cited by this paper
• Large-scale population screening for spinal muscular atrophy: Clinical implications

  2011cited by this paper
• Nuchal translucency measurement in fetuses with spinal muscular atrophy

  2011cited by this paper
• Large-Scale Population Carrier Screening for Spinal Muscular Atrophy in Israel—Effect of Ethnicity on the False-Negative Rate

  2010cited by this paper
• Molecular characterization of SMN copy number derived from carrier screening and from core families with SMA in a Chinese population

  2010cited by this paper
• Newborn and carrier screening for spinal muscular atrophy

  2010cited by this paper
• Carrier testing for spinal muscular atrophy

  2010cited by this paper
• Determination of SMN1 and SMN2 copy numbers in a Korean population using multiplex ligation-dependent probe amplification.

  2010cited by this paper
• Increased nuchal translucency in euploid fetuses—what should we be telling the parents?

  2010cited by this paper
• Deaths: preliminary data for 2008.

  2010cited by this paper
• ACOG committee opinion No. 432: spinal muscular atrophy.

  2009cited by this paper
• Differences in SMN1 allele frequencies among ethnic groups within North America

  2009cited by this paper
• A positive modifier of spinal muscular atrophy in the SMN2 gene.

  2009cited by this paper
• The impact of family history of breast cancer and cancer death on women's mammography practices and beliefs

  2008cited by this paper
• Carrier screening for spinal muscular atrophy

  2008cited by this paper
• Spinal muscular atrophy.

  2008cited by this paper
• Population screening and cascade testing for carriers of SMA

  2007cited by this paper
• Spinal muscular atrophy genotyping by gene dosage using multiple ligation-dependent probe amplification

  2006cited by this paper
• Quantitative analysis of SMN1 and SMN2 genes based on DHPLC: A highly efficient and reliable carrier‐screening test

  2005cited by this paper
• New insights on the evolution of the SMN1 and SMN2 region: simulation and meta-analysis for allele and haplotype frequency calculations

  2004cited by this paper
• Homozygous SMN1 deletions in unaffected family members and modification of the phenotype by SMN2

  2004cited by this paper
• Determination of SMN1 and SMN2 copy number using TaqMan™ technology

  2003cited by this paper
• Spinal muscular atrophy genetic testing experience at an academic medical center.

  2002cited by this paper
• Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy.

  2002cited by this paper
• Hybrids monosomal for human chromosome 5 reveal the presence of a spinal muscular atrophy (SMA) carrier with two SMN1 copies on one chromosome

  2001cited by this paper
• A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy.

  1999cited by this paper
• Quantitative analysis of survival motor neuron copies: identification of subtle SMN1 mutations in patients with spinal muscular atrophy, genotype-phenotype correlation, and implications for genetic counseling.

  1999cited by this paper
• Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number.

  1997cited by this paper
• Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications.

  1995cited by this paper

• Disparities in Spinal Muscular Atrophy-Related Mortality in the United States, 2018-2023.

  2026cites this paper
• Real-world treatment patterns and unmet needs in spinal muscular atrophy: a caregiver-centric survey study from China.

  2026cites this paper
• Sleep in children with spinal muscular atrophy and their caregivers: Exploring sleep problems and the need for care.

  2026cites this paper
• Spinal Muscular Atrophy-Survivorship and Care in a New Therapeutic Landscape.

  2026cites this paper
• CORRELAÇÃO DO USO DE RIDISPLAM COM A ESCALA CHOP INTEND: UMA REVISÃO DE LITERATURA

  2026cites this paper
• From policy to practice: premarital spinal muscular atrophy screening as a public health initiative in northern Türkiye

  2026cites this paper
• Research trends on spinal muscular atrophy from 1995 to 2023: A bibliometric analysis

  2025cites this paper
• Preliminary psychometric validation of patient-reported outcomes relevant to individuals with spinal muscular atrophy and their caregivers

  2025cites this paper
• Prenatal genetic counseling challenges with indeterminate SMA results

  2025cites this paper
• Multisystemic Evaluation in Pediatric Spinal Muscular Atrophy: Linking Biochemical Markers to Functional Outcomes and Family Quality of Life

  2025cites this paper
• An Exploratory 12-Month Observational Study of Adults with Spinal Muscular Atrophy: Learning from our Tools.

  2025cites this paper
• Research Advances in Home Care for Children with Spinal Muscular Atrophy

  2025cites this paper
• Carrier screening for survival motor neuron variants in 7709 pregnant women from Foshan, Guangdong Province.

  2025cites this paper
• A de novo deletion underlying spinal muscular atrophy: implications for carrier testing and genetic counseling

  2025cites this paper
• Prenatal carrier screening for spinal muscular atrophy among pregnant Thai women

  2025cites this paper
• Systemic mRNA-LNP administration in fetuses improves survival in a mouse model of spinal muscular atrophy

  2025cites this paper
• Outcomes of a Pilot Newborn Screening Program for Spinal Muscular Atrophy in the Valencian Community

  2025cites this paper
• Exploring the Prevalence of SMN1 Duplication and Deletion in Russia and Its Impact on Carrier Screening

  2025influential citation
• Pilocytic Astrocytoma in a Child with Spinal Muscular Atrophy Treated with Onasemnogene Abeparvovec.

  2025cites this paper
• Views of the Public and Healthcare Professionals on Newborn Screening for Spinal Muscular Atrophy and the Potential for Detecting Adult-Onset Types in Patients-in-Waiting in Hong Kong

  2025cites this paper
• Genomic analysis of the SMN1 gene region in patients with clinically diagnosed spinal muscular atrophy: a retrospective observational study

  2025cites this paper
• AN EXPLORATORY QUALITATIVE ASSESSMENT OF PATIENT AND CLINICIAN PERSPECTIVES ON PATIENT-REPORTED OUTCOME MEASURES AND DISEASE-MODIFYING THERAPIES IN ADULTS WITH SPINAL MUSCULAR ATROPHY

  2025cites this paper
• Outcomes of genetic testing and prenatal diagnosis of spinal muscular atrophy in Jordan

  2025cites this paper
• Pediatric Pulmonology

  2025cites this paper
• Carrier Screening and Prenatal Diagnosis for Spinal Muscular Atrophy in Ningde City, Fujian Province

  2025cites this paper
• Thrombotic microangiopathy following gene therapy for 5q-spinal muscular atrophy

  2025cites this paper
• TERIPARATIDE IN SEQUENTAL TREATMENT OF OSTEOPOROSIS IN A PATIENT WITH SPINAL MUSCULAR ATROPHY: A CASE REPORT AND LITERATURE REVIEW

  2025cites this paper
• Family doctor and paediatrician care for a patient with spinal muscular atrophy

  2025cites this paper
• Cerebellar defects are a primary pathology in mouse models of spinal muscular atrophy

  2025cites this paper
• Newborn screening for spinal muscular atrophy: The potential of digital polymerase chain reaction technique.

  2025cites this paper
• Comparison of fluoroscopy-guided and blind techniques in intrathecal nusinersen administration

  2025cites this paper
• Clinically Discordant Siblings with Spinal Muscular Atrophy: Insights from Patient-Specific iPSC-Derived Motor Neurons and Literature Review

  2025cites this paper
• Longitudinal evaluation of fatigue in adult patients with spinal muscular atrophy and the impact of disease-modifying drugs

  2025cites this paper
• Managing Spinal Muscular Atrophy: A Look at the Biology and Treatment Strategies

  2025cites this paper
• Elevated Urinary Titin in Adult Spinal Muscular Atrophy: A Multicenter, Cross-Sectional Observational Study

  2025cites this paper
• Genotype Structure Alterations in 5q SMA Patients as a Result of the Newborn Screening Program Implementation in the Russian Federation

  2025cites this paper
• Considerations for repetitive intrathecal procedures in long-term nusinersen treatment for non-ambulatory spinal muscular atrophy

  2025cites this paper
• Fulfilling the needs of caregivers in delivering health services to children with developmental and epileptic encephalopathies.

  2025cites this paper
• Natural History of Spinal Muscular Atrophy Type I

  2025cites this paper
• Calculation of the Minimal Clinically Important Difference in Upper and Lower Limb Motor Assessment in Spinal Muscular Atrophy

  2025cites this paper
• Algoritmo de orientación para la identificación temprana de los signos y síntomas y el diagnóstico de AME 5q 1-3 en Colombia: Panel Delphi Modificado

  2025cites this paper
• Saliva Sample‐Based Non‐Invasive Carrier Screening for Spinal Muscular Atrophy, Hereditary Hearing Loss, and Thalassemia in 13,926 Women of Reproductive Age From South Zhejiang

  2025cites this paper
• Effectiveness and safety of Risdiplam for types 1–3 spinal muscular atrophy in a single center

  2025cites this paper
• Safety and Efficacy of Nusinersen Focusing on Renal and Hematological Parameters in Spinal Muscular Atrophy

  2025cites this paper
• Spinal Muscular Atrophy (SMA): Treatment strategies, challenges and future prospects

  2025cites this paper
• Prenatal SMN-dependent defects in translation uncover reversible primary cilia phenotypes in spinal muscular atrophy

  2025cites this paper
• In utero therapy for spinal muscular atrophy: closer to clinical translation

  2025cites this paper
• A Convenient, Pd-Free Approach to the Synthesis of Risdiplam

  2025cites this paper
• Elucidating the Pathogenic Mechanism of Spinal Muscular Atrophy Through the Investigation of UTS2.

  2025cites this paper
• Real-world analysis of the efficacy and safety of nusinersen in pediatric patients with spinal muscular atrophy

  2025cites this paper
• Assessing disease progression in spinal muscular atrophy, current gaps, and opportunities: a narrative review.

  2025cites this paper
• Evaluating the clinical efficacy of a long-read sequencing-based approach for carrier screening of spinal muscular atrophy

  2024cites this paper
• Current Treatment Process and Challenges for Spinal Muscular Atrophy (SMA)

  2024cites this paper
• Clinical decision making around commercial use of gene and genetic therapies for spinal muscular atrophy

  2024cites this paper
• Clinical significance of Spinal Muscular Atrophy carrier detection in Guangdong Province, China: Insights from quantitative polymerase chain reaction and multiplex ligation-dependent probe amplification analysis

  2024cites this paper
• Intrathecal nusinersen treatment in a Chinese patient with spinal muscular atrophy type 3 after ventriculo-peritoneal shunt placement: A case report and review of literature

  2024cites this paper
• Newborn Screening for Spinal Muscular Atrophy: Variations in Practice and Early Management of Infants with Spinal Muscular Atrophy in the United States

  2024cites this paper
• Secondary outcomes of scoliosis surgery in disease‐modifying treatment‐naïve patients with spinal muscular atrophy type 2 and nonambulant type 3

  2024cites this paper
• Outcomes for patients in the RESTORE registry with spinal muscular atrophy and four or more SMN2 gene copies treated with onasemnogene abeparvovec.

  2024cites this paper
• Timing of SMN replacement therapies in mouse models of spinal muscular atrophy: a systematic review and meta-analysis

  2024cites this paper
• Physiological Features of the Neural Stem Cells Obtained from an Animal Model of Spinal Muscular Atrophy and Their Response to Antioxidant Curcumin

  2024cites this paper
• SMArt Retro study: a retrospective data analysis of the Russian registry of patients with spinal muscular atrophy

  2024cites this paper
• Outcomes of early‐treated infants with spinal muscular atrophy: A multicenter, retrospective cohort study

  2024cites this paper
• SMN1 c.5C>G (p.Ala2Gly) missense variant, a challenging molecular SMA diagnosis associated with mild disease, preserves SMN nuclear gems in patient-specific fibroblasts

  2024cites this paper
• A rapid and easy-to-use spinal muscular atrophy screening tool based on primers with high specificity and amplification efficiency for SMN1 combined with single-stranded tag hybridization assay

  2024cites this paper
• The prevalence of SMN gene deletion/duplication in spinal muscular atrophy families referred to neuro-genetic centers of Mashhad, Iran

  2024cites this paper
• Fiberoptic endoscopic evaluation of swallowing (FEES) in children with spinal muscular atrophy type 1: feasibility, swallowing safety and efficacy, and dysphagia phenotype

  2024cites this paper
• Analysis of blood concentrations and clinical application of risdiplam in patients with spinal muscular atrophy using ultra-high performance liquid chromatography-tandem mass spectrometry.

  2024cites this paper
• Complex SMN Hybrids Detected in a Cohort of 31 Patients With Spinal Muscular Atrophy

  2024cites this paper
• Large-scale neurophysiology and single-cell profiling in human neuroscience

  2024cites this paper
• Analysis of the efficacy and adverse effects of nusinersen in the treatment of children with spinal muscular atrophy in China

  2024cites this paper
• Gene replacement therapy for spinal muscular atrophy: safety and preliminary efficacy in a Brazilian cohort

  2024cites this paper
• The association between gait speed and falls in ambulatory adults with spinal muscular atrophy: a retrospective pilot study

  2024cites this paper
• Therapeutic Role of Nusinersen on Respiratory Progression in Pediatric Patients With Spinal Muscular Atrophy Type 2 and Nonambulant Type 3.

  2024cites this paper
• Analysis of spinal muscular atrophy patients from the spinal muscular atrophy and muscular dystrophy registry of Pakistan

  2024cites this paper
• Peripheral defects precede neuromuscular pathology in the Smn2B/− mouse model of spinal muscular atrophy

  2024cites this paper
• Potential of Cell-Penetrating Peptide-Conjugated Antisense Oligonucleotides for the Treatment of SMA

  2024cites this paper
• Antisense Oligonucleotides (ASOs) in Motor Neuron Diseases: A Road to Cure in Light and Shade

  2024cites this paper
• A Five-Year Review of Newborn Screening for Spinal Muscular Atrophy in the State of Utah: Lessons Learned

  2024cites this paper
• Genetic study on candidates for oocyte donation

  2024cites this paper
• Spinal muscular atrophy: A comprehensive case report

  2024cites this paper
• Analysis of spinal muscular atrophy carrier screening results in 32,416 pregnant women and 7,231 prepregnant women

  2024cites this paper
• A self-reported Brazilian registry of 5q-spinal muscular atrophy: data on natural history, genetic characteristics, and multidisciplinary care

  2024cites this paper
• Motor pool selectivity of neuromuscular degeneration in type I spinal muscular atrophy is conserved between human and mouse

  2024cites this paper
• Knowledge and Awareness of Spinal Muscular Atrophy in Pre-Marital Health Screenings: A Cross-Sectional Study

  2024cites this paper
• Altered mitochondrial function in fibroblast cell lines derived from disease carriers of spinal muscular atrophy

  2024cites this paper
• In Search of Spinal Muscular Atrophy Disease Modifiers

  2024cites this paper
• Variants located in intron 6 of SMN1 lead to misdiagnosis in genetic detection and screening for SMA

  2024cites this paper
• MicroRNAs as Biomarkers in Spinal Muscular Atrophy

  2024cites this paper
• Real-world evidence: Risdiplam in a patient with spinal muscular atrophy type I with a novel splicing mutation and one SMN2 copy

  2024cites this paper
• Diagnosis of challenging spinal muscular atrophy cases with long-read sequencing.

  2024cites this paper
• Clinicogenetic characterization and response to disease-modifying therapies in spinal muscular atrophy: real-world experience from a reference center in Southern Brazil

  2024cites this paper
• A modified glycosylase base editor without predictable DNA off‐target effects

  2024cites this paper
• Newborn Screening and Birth Prevalence for Spinal Muscular Atrophy in the US

  2024cites this paper
• Hereditary Neuromuscular Disorders in Reproductive Medicine

  2024cites this paper
• [Risdiplam for the treatment of spinal muscular atrophy].

  2024cites this paper
• No significant sex differences in incidence or phenotype for the SMNΔ7 mouse model of spinal muscular atrophy.

  2024cites this paper
• Breaking genetic shackles: The advance of base editing in genetic disorder treatment

  2024cites this paper
• Spinal muscular atrophy: Molecular mechanism of pathogenesis, diagnosis, therapeutics, and clinical trials in the Indian context

  2024cites this paper
• Assessment of Barriers to Referral and Appointment Wait Times for the Evaluation of Spinal Muscular Atrophy (SMA): Findings from a Web-Based Physician Survey

  2024cites this paper