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- Title
Targeted next-generation sequencing identification of mutations in patients with disorders of sex development.
- Authors
Yanling Dong; Yuting Yi; Hong Yao; Ziying Yang; Huamei Hu; Jiucheng Liu; Changxin Gao; Ming Zhang; Liying Zhou; Asan; Xin Yi; Zhiqing Liang
- Abstract
Background: The identification of causative mutations is important for treatment decisions and genetic counseling of patients with disorders of sex development (DSD). Here, we designed a new assay based on targeted nextgeneration sequencing (NGS) to diagnose these genetically heterogeneous disorders. Methods: All coding regions and flanking sequences of 219 genes implicated in DSD were designed to be included on a panel. A total of 45 samples were used for sex chromosome dosage validation by targeted sequencing using the NGS platform. Among these, 21 samples were processed to find the causative mutation. Results: The sex chromosome dosages of all 45 samples in this assay were concordant with their corresponding karyotyping results. Among the 21 DSD patients, a total of 11 mutations in SRY, NR0B1, AR, CYP17A1, GK, CHD7, and SRD5A2 were identified, including five single nucleotide variants, three InDels, one in-frame duplication, one SRYpositive 46,XX, and one gross duplication with an estimated size of more than 427,038 bp containing NR0B1 and GK. We also identified six novel mutations: c.230_231insA in SRY, c.7389delA in CHD7, c.273C>G in NR0B1, and c.2158G>A, c.1825A>G, and c.2057_2065dupTGTGTGCTG in AR. Conclusions: Our assay was able to make a genetic diagnosis for eight DSD patients (38.1%), and identified variants of uncertain clinical significance in the other three cases (14.3%). Targeted NGS is therefore a comprehensive and efficient method to diagnose DSD. This work also expands the pathogenic mutation spectrum of DSD.
- Subjects
GENETIC mutation; GENETIC counseling; SEX differentiation disorders; SEX chromosomes; KARYOTYPES
- Publication
BMC Medical Genetics, 2016, Vol 17, p1
- ISSN
1471-2350
- Publication type
Article
- DOI
10.1186/s12881-016-0286-2