{Reference Type}: Journal Article
{Title}: 28 novel mutations identified from 33 Chinese patients with cilia-related kidney disorders.
{Author}: Liang N;Jiang X;Zeng L;Li Z;Liang D;Wu L;
{Journal}: Clin Chim Acta
{Volume}: 501
{Issue}: 0
{Year}: Feb 2020
{Factor}: 6.314
{DOI}: 10.1016/j.cca.2019.10.040
{Abstract}: <B>BACKGROUND: </B>Cilia play an important role in cellular signaling pathways. Defective ciliary function causes a variety of disorders involve retina, skeleton, liver, kidney or others. Cilia-related kidney disorders are characterized by cystic renal disease, nephronophthisis and renal failure in general.<BR><B>METHODS: </B>In this study, we collected 33 families clinically suspected of cilia-related kidney disorders. Capture-based next-generation sequencing (NGS) of 88 related genes, Sanger sequencing, pedigree analysis and functional study were performed to analyze their genetic cause.<BR><B>RESULTS: </B>40 mutations in PKD1, PKD2, PKHD1, DYNC2H1 and TMEM67 genes were identified from 27 of 33 affected families. 70% (28/40) of the mutations were first found in patients. We reported a very early-onset autosomal dominant polycystic kidney disease (ADPKD) family caused by a novel heterozygous PKD1 mutation; another fetus with DYNC2H1 compound heterozygous missense mutations showed mainly kidney dysplasia instead of skeletal abnormalities; and a novel PKD1 mutation, c.12445-3C > G, was confirmed to cause two wrong splicing modes. As for previously reported mutations, such as PKD1, c.6395 T > G (p.F2132C) and c.6868G > T (p.D2290Y), we had new and different findings.<BR><B>CONCLUSIONS: </B>The findings provided new references for genotype-phenotype analyses and broadened the mutation spectrum of detected genes, which were significantly valuable for prenatal diagnosis and genetic counseling.