Abstract
Background:
Alport syndrome (AS) is a genetically heterogeneous disorder that is characterized by hematuria, progressive renal failure typically resulting in end-stage renal disease, sensorineural hearing loss, and variable ocular abnormalities. Only 15% of cases with AS are autosomal recessive and are caused by mutations in the
COL4A3
or
COL4A4
genes, encoding type IV collagen.
Methods:
Clinical data in a large consanguineous family with four affected members were reviewed, and genomic DNA was extracted. For mapping, 15 microsatellite markers flanking
COL4A3
,
COL4A4
, and
COL4A5
in 16 family members were typed. For mutation screening, all coding exons of
COL4A3
were polymerase chain reaction- amplified and Sanger-sequenced from genomic DNA.
Results:
The disease locus was mapped to chromosome 2q36.3, where
COL4A3
and
COL4A4
reside. Sanger sequencing revealed a novel mis-sense mutation (c.2T>C; p.M1T) in exon 1 of
COL4A3
. The identified nucleotide change was not found in 100 healthy ethnicity-matched controls via Sanger sequencing.
Conclusions:
We present a large consanguineous Turkish family with AS that was found to have a
COL4A3
mutation as the cause of the disease. Although the relationship between the various genotypes and phenotypes in AS has not been fully elucidated, detailed clinical and molecular analyses are helpful for providing data to be used in genetic counseling. It is important to identify new mutations to clarify their clinical importance, to assess the prognosis of the disease, and to avoid renal biopsy for final diagnosis.
