en Clinical Medicine Clinical Medicine گزارش موردی Case Report Article <p style="text-align: justify;"><span style="font-size:16px;"><span style="font-family:Times New Roman;"><span lang="EN-GB"><span style="color:black">Alport syndrome (AS) is an inherited disorder of collagen type IV</span></span><span style="color:black"> causing</span><span lang="EN-GB"><span style="color:black"> progressive renal disease, sensorineural hearing loss, and ocular abnormalities with variable severity.</span></span> <span lang="EN-GB"><span style="color:black">Here, we report a splice site variant in the <i>COL4A5</i> gene, leading to X-linked Alport syndrome (XLAS) in two </span></span><span style="color:black">siblings from a non-consanguineous Iranian family. </span><span lang="EN-GB"><span style="color:black">The proband was a 10-year-old boy with hematuria, proteinuria, and mild to moderate bilateral sensorineural hearing loss (BSNHL), who was diagnosed with AS based on renal pathology and genetic testing.</span></span> <span lang="EN-GB"><span style="color:black">Whole exome sequencing of the proband identified a hemizygous canonical splice site variant (c.4994+1G>A) in intron 52 of the <i>COL4A5</i> gene. The same mutation was detected in </span></span><span style="color:black">his affected brother and </span><span lang="EN-GB"><span style="color:black">heterozygous mother by Sanger sequencing</span></span><span style="color:black">, </span><span lang="EN-GB"><span style="color:black">confirming the diagnosis of XLAS in the two affected individuals with renal impairment in this family.</span></span><span style="color:black"> Our findings expand the geographic and mutational spectrum of <i>COL4A5</i> splice site variants. To the best of our knowledge, this is the first reported c.4994+1G>A variant (ClinVar: rs2524654509) in an Iranian family, underscoring the need for including splice site analysis in diagnostic testing.</span></span></span></p> Alport Syndrome, COL4A5 Protein, Human, RNA Splice Sites, Collagen Type IV, Exome Sequencing 341 347 http://journal.zums.ac.ir/browse.php?a_code=A-10-7202-1&slc_lang=en&sid=1 Amirhossein Abyar amirabiar@gmail.com 5200319475328460085854 0009-0006-5973-7228 No Department of Genetics and Molecular Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Akbar Mohammadzadeh akbarmohammadzadeh1348@gmail.com 5200319475328460085855 5200319475328460085855 No Department of Genetics and Molecular Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran Reyhaneh Dehghanzad reyhanedehghanzad71@gmail.com 5200319475328460085856 5200319475328460085856 No Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Mohammad Keramatipour m@keramati.org 5200319475328460085857 5200319475328460085857 Yes Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran