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Long‐term clinicopathologic observation in a case of steroid‐resistant nephrotic syndrome caused by a novel Crumbs homolog 2 mutation
Author(s) -
Watanabe Shojiro,
Aizawa Tomomi,
Tsukaguchi Hiroyasu,
Tsugawa Koji,
Tsuruga Kazushi,
Shono Akemi,
Nozu Kandai,
Iijima Kazumoto,
Joh Kensuke,
Tanaka Hiroshi
Publication year - 2018
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/nep.13244
Subject(s) - medicine , nephrotic syndrome , focal segmental glomerulosclerosis , biopsy , renal biopsy , mutation , minimal change disease , compound heterozygosity , phenotype , pathology , renal function , genetic testing , gastroenterology , glomerulonephritis , kidney , genetics , biology , gene
Recent advances in high‐throughput sequencing for clinical genetic testing have revealed novel disease‐causing genes, such as Crumbs homolog 2 ( CRB2 ) for early‐onset steroid‐resistant nephrotic syndrome (SRNS). We report the long‐term clinicopathologic observation of a Japanese female patient with SRNS caused by a newly identified compound heterozygous mutation of CRB2 (p.Arg628Cys and p.Gly839Trp located in the 10th and 11th epidermal growth factor‐like domains, respectively). She was initially examined during a mass urinary screening for 3.5‐year‐old children in Japan. Although she developed long‐standing SRNS without any extrarenal clinical signs thereafter, her renal function was well‐preserved over the next 17 years. In total, six sequential renal biopsy specimens revealed histologic alterations ranging from minor glomerular abnormalities to advanced focal segmental glomerulosclerosis (FSGS). A genetic analysis for SRNS performed at 19 years of age revealed a newly identified compound heterozygous mutation in CRB2 . Glomerular CRB2 immunoreactivity in biopsy specimens from the patient was scanty, whereas intense expression was observed in those from patients with idiopathic FSGS or in controls. To our knowledge, this is the first report regarding a long‐term outcome in a case of SRNS due to an identified CRB2 mutation. Although the phenotype of CRB2 mutation‐related syndrome is now expanding, we believe that this case might provide a novel clinicopathologic aspect of this syndrome.