Related Experiment Video
Updated: Apr 21, 2026
A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
Exome sequencing for the diagnosis of 46,XY disorders of sex development
Ruth M Baxter1, Valerie A Arboleda, Hane Lee
1Departments of Human Genetics (R.M.B., V.A.A., H.B., A.E., S.F.N., E.D., E.V.) and Pathology and Laboratory Medicine (V.A.A., H.L., S.F.N.), David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California 90095; Department of Pediatrics (M.P.A.), University of Washington, Seattle, Washington 98195; Department of Endocrinology (P.Y.F.), Seattle Children's Hospital, Seattle, Washington 98105; Nassau University Medical Center (R.B.), East Meadow, New York 11554; Departments of Pediatrics and Human Genetics (C.K.), Ann Arbor, Michigan 48109; The Children's Hospital Colorado (S.T.), Aurora, Colorado 80045; Division of Medical Genetics (S.S., L.H.), Stanford University, Lucile Packard Children's Hospital, Stanford, California 94305; TriStar Children's Specialists (R.P.M.), Nashville, Tennessee 37203; Division of Pediatric Genetics and Metabolism (H.J.S., R.Z.), University of Florida, Gainesville, Florida 32610; Cedars-Sinai Medical Center (O.K.G.), Los Angeles, California 90048; Children's Hospital of Los Angeles (L.R.-P.), Los Angeles, California 90027; and Departments of Pediatrics (A.P.-H., E.D., E.V.) and Urology (E.V.), David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California 90095.
Context:
Disorders of sex development (DSD) are clinical conditions where there is a discrepancy between the chromosomal sex and the phenotypic (gonadal or genital) sex of an individual. Such conditions can be stressful for patients and their families and have historically been difficult to diagnose, especially at the genetic level. In particular, for cases of 46,XY gonadal dysgenesis, once variants in SRY and NR5A1 have been ruled out, there are few other single gene tests available.
Objective:
We used exome sequencing followed by analysis with a list of all known human DSD-associated genes to investigate the underlying genetic etiology of 46,XY DSD patients who had not previously received a genetic diagnosis.
Design:
Samples were either submitted to the research laboratory or submitted as clinical samples to the UCLA Clinical Genomic Center. Sequencing data were filtered using a list of genes known to be involved in DSD.
Results:
We were able to identify a likely genetic diagnosis in more than a third of cases, including 22.5% with a pathogenic finding, an additional 12.5% with likely pathogenic findings, and 15% with variants of unknown clinical significance.
Conclusions:
Early identification of the genetic cause of a DSD will in many cases streamline and direct the clinical management of the patient, with more focused endocrine and imaging studies and better-informed surgical decisions. Exome sequencing proved an efficient method toward such a goal in 46,XY DSD patients.
More Related Videos
08:22A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
Published on: December 1, 2017
09:30Pre-Implantation Genetic Testing for Aneuploidy on a Semiconductor Based Next-Generation Sequencing Platform
Published on: August 17, 2022
Related Concept Videos
01:43Sex-linked Disorders
02:32X and Y Chromosomes
The germline cells such as egg and sperm cells carry only half the number of chromosomes, i.e., 22 autosomes and one sex chromosome. All eggs have an X chromosome, while sperm cells can carry an X or...
01:43Sex Linked Disorders
01:17Karyotyping
02:45The Ratio of X Chromosome to Autosomes
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female...
01:35Pedigree Analysis