Alport syndrome in Romani

Introduction: Romani people have a high prevalence of kidney failure. This study examined a Romani cohort for pathogenic variants in the COL4A3, COL4A4, and COL4A5 genes which are affected in Alport syndrome a common cause of genetic kidney disease characterized by haematuria, proteinuria, end-stage kidney failure, hearing loss and eye anomalies. Materials and Methods: The study included 57 Romani from different families with clinical features that suggested Alport syndrome who underwent next-generation sequencing of the COL4A3, COL4A4, COL4A5 genes and 83 family members. Results: Twenty-seven Romani (19 %) had autosomal recessive Alport syndrome caused by a homozygous pathogenic c.1598G>A, p.Gly533Asp variant in COL4A4 (n=20) or a homozygous c.415G>C, p.Gly139Arg variant in COL4A3 (n = 7). In addition, there were 83 individuals heterozygous for one of these variants, with 70 (84%) heterozygous for p.Gly533Asp in COL4A4 and 13 (16%) for p.Gly139Arg in COL4A3 (Table 1), consistent with the diagnosis of AD AS or thin basement membrane nephropathy. Conclusions: These two founder variants contribute to the high prevalence of kidney failure in Czech Romani. The estimated population frequency of autosomal recessive Alport syndrome from these variants and consanguinity by descent is at least one:11,000 in Czech Romani.