Whole-exome sequencing identifies a novel compound heterozygous mutation of ANKS6 gene in a Chinese nephronophthisis patient

Abstract Background Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that leads to renal failure in childhood or adolescence. NPHP and the related syndromes have been termed 'ciliopathies' because most NPHP gene products localize to the cilium or its associated structures. Methods Here, we report a 2-year and 11-month-old Chinese girl with end-stage renal disease (ESRD), severe anemia, thrombocytopenia and myocardial hypertrophy. We performed trio-whole-exome sequencing to identify the causative variant of this patient. Results We identified an unreported compound heterozygous mutation (c.2420dupT, p.Thr808Aspfs*2 and c.1973-1G>A) in ANKS6 in the proband. The frameshift mutation c.2420dupT of ANKS6 was inherited from the proband’s unaffected father and the splicing mutation c.1973-1G>A of ANKS6 was inherited from the proband’s unaffected mother. Homozygous mutation in ANKS6 leads to NPHP16 (OMIM#615382) and this is the first case with a compound heterozygous mutation in the NPHP16 gene. Conclusion We have identified a patient with ANKS6 variants in the East-Asian population for the first time. This case report expands the clinical and genetic spectra of NPHP and emphasizes the usefulness of whole-exome sequencing for genetic diagnosis of kidney disease.