AUTHOR=Zhong Zhengxia , Yan Xiaoyong , Fang Zhengying , Dong Yijun , Tan Jiaxing , Xie Jingyuan , Hu Linhong , Zhang Shibin , Qin Wei 

TITLE=Case Report: Adolescent-Onset Isolated Nephronophthisis Caused by a Novel Homozygous Inversin Mutation

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.847397

DOI=10.3389/fgene.2022.847397

ISSN=1664-8021

ABSTRACT=<p><bold>Objective:</bold> Nephronophthisis (NPHP) is a rare autosomal recessive inherited kidney disease that can cause cystic enlargement of the kidneys, and lead to end-stage renal disease (ESRD) before the age of 30 years. Herein we describe a case of adolescent-onset NPHP with a novel homozygous mutation in the inversin gene (<italic>INVS</italic>).</p><p><bold>Methods:</bold> The patient was a 15-year-old Chinese boy who presented with ESRD. Genetic testing was performed via whole exome sequencing and validated <italic>via</italic> Sanger sequencing. A novel homozygous <italic>INVS</italic> mutation was identified (c. 1909C &gt; T; p. Gln637Ter).</p><p><bold>Results:</bold> The results of laboratory examinations included urinary protein 1.05 g/24 h, urine erythrocyte count 5/high-power field, serum creatinine 1,026.2 μmol/L, and estimated glomerular filtration rate 5.8 ml/min/1.73 mm<sup>2</sup>. Extrarenal features included hypertension and moderate anemia, and his parents were consanguineous (first cousins). A homozygous 1-bp substitution resulting in a nonsense mutation (c. 1909C &gt; T; p. Gln637Ter) in exon 15 of <italic>INVS</italic> was detected via whole exome sequencing, and validated via Sanger sequencing. According to the classification system of the American College of Medical Genetics and Genomics, the mutated gene in <italic>INVS</italic> is strongly pathogenic (PVS1+PM2+<italic>P</italic>P3+<italic>P</italic>P5). His parents and a younger brother were heterozygous carriers. Based on the above results he was diagnosed with juvenile type 2 NPHP. He underwent hemodialysis, and received a kidney transplant after 2 months. He is currently recovering well, with a serum creatinine level of 117 μmol/L and an estimated glomerular filtration rate of 79.6 ml/min/1.73 mm<sup>2</sup>.</p><p><bold>Conclusion:</bold> Here we have described an extremely rare case of adolescent-onset type 2 NPHP caused by a homozygous <italic>INVS</italic> mutation. The patient had progressed to ESRD by the age of 15 years. The current report will deepen our understanding of the clinical and genetic basis of this disease.</p>