Table 1.
Clinical and pathologic findings
| Patient ID | Sex | Age (yr) | ESRD Age (yr) | Hearing Loss (Detected Age) | sCr (mg/dl) | U-P/Cr (g/g) | eGFR | EM | α5 | Family History | Mutation Position | Nucleotide Change | Transcript | Truncating Mutation | Expected Change |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Splicing acceptor site mutations | |||||||||||||||
| 7 | M | 25 | 9 | Mild | ESRD | — | — | BWC | Negative | Mother: OB | Intron 10 | IVS11−2a>t | 19-bp deletion (frame shift) | Yes | Exon 11 skipping (36 bp) |
| 17 | W | 11 | — | — | 0.35 | 1 | 151 | BWC | Mosaic | None | Intron 38 | IVS39−1g>a | 1-bp deletion (frame shift) | Yes | Exon 39 skipping (99 bp) |
| 27 | M | 5 | — | — | 0.21 | 0.71 | 155 | BWC | Negative | None | Intron 18 | IVS18−1g>a | 1-bp deletion (frame shift) | Yes | Exon 18 skipping (42 bp) |
| 28 | W | 6 | — | — | 0.32 | 0.2 | 158 | TBM | Mosaic | Sister: OB | Intron 27 | IVS28−2a>g | 18-bp deletion | No | Exon 28 skipping (98 bp) |
| 128 | M | 46 | — | Mild | 1.53 | 1.07 | 41 | ND | Negative (skin) | Brother: 40 yr ESRD; daughters: OB | Intron 26 | IVS27−18a>g | 105-bp deletion (exon 27 skipping) | No | — |
| 158 | W | 14 | — | — | 0.53 | 0.35 | 114 | BWC | Mosaic | None | Intron 28 | IVS29−8t>a | 6-bp insertion | No | Exon 29 skipping (151 bp) |
| Exonic mutation | |||||||||||||||
| 21 | M | 41 | 24 | Mild | ESRD | — | — | BWC | Negative | Grandfather: 20 yr ESRD; mother: OB | Exon 41 | c.3790G>A | 186-bp deletion (exon 41 skipping) | No | Missense mutation |
| Deep intronic mutations | |||||||||||||||
| 19 | M | 22 | — | Mild | 0.56 | 0.55 | 98 | BWC | Negative | Mother: pro/OB | Intron 25 | IVS25+894c>g | 106-bp insertion with stop codona | Yes | — |
| 48 | M | 6 | — | — | 0.3 | 1.87 | 122 | ND | Negative (skin) | Mother: 28 yr ESRD | Intron 47 | IVS48−345a>g | 74-bp insertion with stop codon | Yes | — |
| 126 | M | 12 | — | Severe | 0.79 | 0.24 | 96 | BWC | Negative | Mother: OB; sister: OB | Intron 10 | IVS10+875g>t | 123-bp insertion with stop codon | Yes | — |
| 217 | M | 4 | — | — | 0.88 | 0.5 | 50 | BWC | Negative | Mother and sisters: pro/OB | Intron 47 | IVS47+1754t>g | 84-bp insertion with stop codon | Yes | — |
M, man; W, woman; sCr, serum creatinine; U-P/Cr, urinary protein-to-creatinine ratio; EM, electron microscopic findings; BWC, basket-weave change; ND, not determined; OB, occult blood; pro, protein; TBM, thin basement membrane.
a
RT-PCR results showed both normal and abnormal transcripts only in cDNA extracted from the kidney, and this case showed an extremely mild phenotype for a man with X-linked Alport syndrome with a truncating mutation.