Diagnosis of one case of Williams-Beuren syndrome presenting with hypothyroidism by low-coverage massively parallel CNV sequencing

Objective To explore the clinical phenotypes and the genetic causes for a 5 years old boy with unexplained growth retardation, developmental delay, special face, and hypothyroidism. Methods Routine G-banding was performed to analyze the karyotype of the patient and his parents. In addition, whole exome sequencing and low-coverage massively parallel CNV sequencing (CNV-seq) were used to determine the potentially pathogenic variants as well as the copy number variations (CNVs). Results The child′s karyotype was 46, XY, and his parents′ karyotypes were normal.However, CNV-seq identified a heterozygous deletion of 1.56 Mb on chromosome region 7q11.23 in the patient, including 24 protein-coding genes, which were associated with Williams-Beuren syndrome. His parents′ results of CNV-seq were normal, indicating a de novo CNVs. Conclusion A Williams-Beuren syndrome child presenting with hypothyroidism was diagnosed by CNV-seq, which would contribute to further understanding the clinical phenotypes and pathogenesis of this disease. Key words: Hypothyroidism; Low-coverage massively parallel copy number variation sequencing; Williams-Beuren syndrome; Copy number variations