A novel splice site mutation in the COL4A5 gene in a Chinese female patient with rare ocular abnormalities.
OBJECTIVE
To describe an unusual ocular phenotype in a Chinese female patient with X-linked Alport syndrome (XLAS), and to characterize the type IV collagen alpha 5 (COL4A5) gene mutation in the patient and her son.


METHODS
Detailed ophthalmologic examinations and optical coherence tomography were performed in the patient and her family members. For gene analysis of COL4A5, the entire coding region of COL4A5 mRNA from cultured skin fibroblast was analyzed by using reverse-transcription-polymerase chain reaction (RT-PCR) and direct sequencing, and genomic DNA was analyzed by using PCR and direct sequencing.


RESULTS
The patient presented with progressive myopia at age 14 and bilateral giant macular holes (about 2 disc diameter) at age 28. At age 33 when presented to our hospital, slit lamp examination of the anterior segment showed bilateral anterior and posterior lenticonus; fundus photography and optical coherence tomography showed bilateral giant macular holes which were larger than photographed at age 28. Electron microscopy of renal biopsy showed irregular thinned and thickened areas of the glomerular basement membrane with splitting of the lamina densa. Her son was then found to have hematuria (at age 3), and indirect immunofluorescence of the epidermal basement membrane showed negative staining for the collagen α5(IV) chain. However, the ophthalmological examinations of her son were unremarkable. A novel COL4A5 mutation g. 4400_4400+1del, leading to an indel in exon 45 (r. 4198delins4198+2_ 4198+72), was detected in the patient and her son. This mutation produces a shift in the reading frame, resulting in a missense sequence of 13 codons followed by a premature stop codon. Her mother was not affected with the mutation.


CONCLUSIONS
Our report extends the phenotypic and genotypic spectrum of X-linked Alport syndrome.
Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China.
Chan
C
Zhao
Fang
F
Wang
Yanqin
Y
Zhang
Yubing
Y
Wen
Ying
Y
Su
Chengfen
C
Zhang
Ruifang
R
Sui
Fei
F
Xu
Jie
J
Ding
Fangtian
F
Dong
D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002478:Cells, Cultured; D002675:Child, Preschool; D024141:Collagen Type IV / Q000235:genetics*; D005091:Exons; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D016368:Frameshift Mutation; D005838:Genotype; D006417:Hematuria / Q000150:complications / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009394:Nephritis, Hereditary / Q000150:complications / Q000235:genetics*; D016366:Open Reading Frames; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
C478159:COL4A5 protein, human; D024141:Collagen Type IV