Clinical Diagnosis by Whole-Genome Sequencing of a Prenatal Sample

• Published in: The New England journal of medicine Vol. 367; no. 23; pp. 2226 - 2232
• Main Authors: Talkowski, Michael E, Ordulu, Zehra, Pillalamarri, Vamsee, Benson, Carol B, Blumenthal, Ian, Connolly, Susan, Hanscom, Carrie, Hussain, Naveed, Pereira, Shahrin, Picker, Jonathan, Rosenfeld, Jill A, Shaffer, Lisa G, Wilkins-Haug, Louise E, Gusella, James F, Morton, Cynthia C
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 06.12.2012
• Series: Brief Report
• Subjects: Adult; Amniocentesis; Biological and medical sciences; Cesarean section; CHARGE syndrome; CHARGE Syndrome - diagnosis; CHARGE Syndrome - genetics; Chromosome Aberrations; Chromosome Disorders - diagnosis; Congenital diseases; Deoxyribonucleic acid; Diagnosis; DNA; DNA sequencing; Female; Fetal Diseases - diagnosis; Fetuses; General aspects; Genetic counseling; Genetic Testing - methods; Genome, Human; Genomes; Genomic Library; Heart Defects, Congenital - diagnostic imaging; Heart Defects, Congenital - genetics; Humans; Karyotype; Medical diagnosis; Medical sciences; Metabolism; Mutation; Oligonucleotide Array Sequence Analysis; Pregnancy; Prenatal care; Prenatal Diagnosis - methods; Translocation, Genetic; Ultrasonic imaging; Ultrasonography, Prenatal; Ultrasound; Whole genome sequencing; United States > US; Medicine; Prenatal; Diagnosis; Nucleotide sequence; Genome; Sequencing
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa1208594

Translocation of chromosomes can result in disruption of genes. In this case report, a sequencing approach was used to identify the cause and effect of a translocation within 13 days, a period consistent with use of the approach in prenatal diagnosis. Deep sequencing of the whole genome holds diagnostic promise but is currently thought to be impractical for routine prenatal care. In contrast, large-insert mate-pair, or jumping-library, sequencing provides a tractable approach for immediate clinical application and could complement conventional prenatal diagnostics. The risk of major structural birth defects among live births in the United States is approximately 3% 1 and is associated with inherited or de novo genetic rearrangements and mutations as well as with maternal factors, such as advanced age, certain clinical conditions, and exposure to teratogenic factors. Approximately 1 in 2000 prenatal cases analyzed with conventional karyotyping has a . . .