Causal variants screened by whole exome sequencing in a patient with maternal uniparental isodisomy of chromosome 10 and a complicated phenotype

Li,Niu; Ding,Yu; Yu,Tingting; Li,Juan; Shen,Yongnian; Wang,Xiumin; Fu,Qihua; Shen,Yiping; Huang,Xiaodong; Wang,Jian

doi:10.3892/etm.2016.3241

Causal variants screened by whole exome sequencing in a patient with maternal uniparental isodisomy of chromosome 10 and a complicated phenotype

Authors:
- Niu Li
- Yu Ding
- Tingting Yu
- Juan Li
- Yongnian Shen
- Xiumin Wang
- Qihua Fu
- Yiping Shen
- Xiaodong Huang
- Jian Wang
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Affiliations: Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, P.R. China, Department of Endocrinology and Metabolism, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, P.R. China
Published online on: April 11, 2016 https://doi.org/10.3892/etm.2016.3241
Pages: 2247-2253
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Uniparental disomy (UPD), which is the abnormal situation in which both copies of a chromosomal pair have been inherited from one parent, may cause clinical abnormalities by affecting genomic imprinting or causing autosomal recessive variation. Whole Exome Sequencing (WES) and chromosomal microarray analysis (CMA) are powerful technologies used to search for underlying causal variants. In the present study, WES was used to screen for candidate causal variants in the genome of a Chinese pediatric patient, who had been shown by CMA to have maternal uniparental isodisomy of chromosome 10. This was associated with numerous severe medical problems, including bilateral deafness, binocular blindness, stunted growth and leukoderma. A total of 13 rare homozygous variants of these genes were identified on chromosome 10. These included a classical splice variant in the HPS1 gene (c.398+5G>A), which causes Hermansky‑Pudlak syndrome type 1 and may explain the patient's ocular and dermal disorders. In addition, six likely pathogenic genes on other chromosomes were found to be associated with the subject's ocular and aural disorders by phenotypic analysis. The results of the present study demonstrated that WES and CMA may be successfully combined in order to identify candidate causal genes. Furthermore, a connection between phenotype and genotype was established in this patient.

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