Sporadic case of X-chromosomal Alport syndrome in a consanguineous family

Abstract

Alport syndrome (AS) is a genetic disorder of basement membranes caused by mutations in type IV collagen genes that is characterized by chronic hematuria and progressive nephropathy leading to renal failure. The main extrarenal features include sensorineural hearing loss and ocular lesions. The mode of inheritance is X-linked dominant in about 80%-85% of the affected families, whereas autosomal transmission is rarely encountered. We report a male patient originating from a healthy consanguineous Lebanese family who presented with an unusual association of obstructive uropathy and AS. Hematuria and proteinuria were initially attributed to a suspected poststreptococcal glomerulonephritis (GN) and high-grade subpelvic ureteral stenosis. Persistence of symptoms after medical treatment of poststreptococcal GN and surgical correction of obstructive uropathy finally led to renal biopsy. The observed ultrastructural changes of the glomerular basement membrane were typical for AS. Molecular genetic studies revealed a previously undescribed de novo mutation in the COL4A5 gene, excluding maternal heterozygotic carrier status. This case report emphasizes the importance of hereditary nephritis in the differential diagnosis of chronic hematuria, and demonstrates the value of molecular studies for genetic counselling in AS.

The Alport nephropathy: clinicopathological correlations

“…Of the 12 biopsies obtained from children without a family history of renal disease, 8 showed grade 3 and 4 grade 2 GBM thickening. Yoshikawa et al [12,26] suggested that these may represent new mutants, as has since been confirmed in a sporadic example occurring in a consanguineous family, by the finding of a COL4A5 mutation not present in the child's mother [27]. However, in the light of the reported mutations in COL4A3 and COL4A4 genes [4], they may instead be examples of autosomal recessive inheritance.…”

Sporadic Case of Heterozygous X-Linked Alport Syndrome

“…In this case, despite some history of familial hematuria, the patient’s mutation was sporadic and not shared by either parent. Such disease-causing sporadic mutations have been characterized to occur; however, there are limited data on the frequency of such events [ 17 , 18 ].…”