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

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.