{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:36:15Z","timestamp":1762079775375,"version":"build-2065373602"},"reference-count":19,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,4]],"date-time":"2022-12-04T00:00:00Z","timestamp":1670112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Nephrotic syndrome (NS) is a kidney disease where the patient has a classic triad of signs and symptoms including hypercholesterolemia, hypoalbuminemia, proteinuria (&gt;3.5 g\/24 h), and peripheral edema. In case of NS, the damaged nephrons (structural and functional unit of the kidney) filter unwanted blood contents to make urine. Thus, the urine contains unwanted proteins (proteinuria) and blood cells (hematuria), while the bloodstream lacks enough protein albumin (hypoalbuminemia). Nephrotic syndrome is divided into two types, primary NS, and secondary NS. Primary NS, also known as primary glomerulonephrosis, is the result of a glomerular disease that is limited to the kidney, while secondary NS is a condition that affects the kidney and other parts of the body. The main causes of primary NS are minimal change disease, membranous glomerulonephritis, and focal segmental glomerulosclerosis. In the present study we recruited a family segregating primary NS with the aim to identify the underlying genetic etiology. Such type of study is important in children because it allows counseling of other family members who may be at risk of developing NS, predicts risk of recurrent disease phenotypes after kidney transplant, and predicts response to immunosuppressive therapy. Materials and Methods: All affected individuals were clinically evaluated. Clinical examination, results of laboratory tests, and biopsy investigations led us to the diagnosis. The next-generation sequencing technique (whole-exome sequencing) followed by Sanger sequencing identified a novel homozygous splice site variant (NM_173689.7: c.941-3C&gt;T) in the CRB2 gene. The variant was present in a homozygous state in the affected individuals, while in a heterozygous state in phenotypically normal parents. Results: The study expanded the spectrum of the mutations in the gene CRB2 responsible for causing NS. Conclusions: In addition, the study will also help in genetic counseling, carrier testing, and prenatal and\/or postnatal early diagnosis of the disease in the affected family.<\/jats:p>","DOI":"10.3390\/medicina58121784","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T02:56:26Z","timestamp":1670208986000},"page":"1784","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exome Sequencing Revealed a Novel Splice Site Variant in the CRB2 Gene Underlying Nephrotic Syndrome"],"prefix":"10.3390","volume":"58","author":[{"given":"Anam","family":"Simaab","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University (QAU), Islamabad 45320, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jai","family":"Krishin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pakistan Institute of Medical Sciences, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad 44000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sultan Rashid","family":"Alaradi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Sciences, Al Wajh General Hospital, Al-Wajh City 48722, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nighat","family":"Haider","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pakistan Institute of Medical Sciences, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad 44000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muqadar","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pakistan Institute of Medical Sciences, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad 44000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asmat","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pakistan Institute of Medical Sciences, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad 44000, Pakistan"},{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdullah","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University (QAU), Islamabad 45320, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wasim","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University (QAU), Islamabad 45320, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torben","family":"Hansen","sequence":"additional","affiliation":[{"name":"Center for Genetics and Inherited Diseases, Taibah University, Medina 42318, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4294-6825","authenticated-orcid":false,"given":"Sulman","family":"Basit","sequence":"additional","affiliation":[{"name":"Center for Genetics and Inherited Diseases, Taibah University, Medina 42318, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ajhg.2014.11.014","article-title":"Defects of CRB2 cause steroid-resistant nephrotic syndrome","volume":"96","author":"Ebarasi","year":"2015","journal-title":"Am. 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