Open AccessA novel compound heterozygous COL4A4 mutation in a Chinese family with Alport syndrome
Author(s) -
Jiyu Chen,
Jingjing Cui,
Xiran Yang,
Yanfang Li,
Yanhua Zhang,
Jiani Chen,
Junyu Lin,
Bo Zhao
Publication year - 2021
Publication title -
medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 148
eISSN - 1536-5964
pISSN - 0025-7974
DOI - 10.1097/md.0000000000027890
Subject(s) - alport syndrome , medicine , compound heterozygosity , proteinuria , mutation , splice site mutation , gene mutation , kidney disease , kidney , pathology , glomerulonephritis , genetics , gene , exon , alternative splicing , biology
Rationale: Alport syndrome (AS) is an inherited progressive renal failure, characterized by kidney disease, hearing loss, and eye abnormalities. Patient concerns: A 7-year-old male child was admitted for persistent microscopic hematuria and proteinuria. Diagnoses: Combined with clinical manifestations, laboratory testing, pathological changes of kidney and sequencing results, the patient was diagnosed as AS. Interventions: The patient was treated with ACEI and tacrolimus drugs for 2 years, but continued to have hematuria and proteinuria. Thus, a genetic analysis was performed using next-generation sequencing in four affected members from the family. Outcomes: The findings revealed triple compound heterozygous mutation of COL4A4 : three novel variations, c.1045C>T (p. R349X), c.3505+1G>A (splicing), and c.2165G>A (p. G722D). Lessons: This study was novel in finding that a triple variant of the COL4A4 gene simultaneously in trans and in cis. The effects of multiple mutation sites and the type of gene mutation in AS were also underlined.