A female with X-linked Alport syndrome and compound heterozygous COL4A5 mutations
Background Female subjects with X-linked Alport syndrome have a single COL4A5 mutation, germ cell mosaicism in affected tissues and typically develop renal failure later or less often than male subjects. Women with two mutations are exceedingly rare, and usually have consanguineous parents or unipar...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English English |
| Published: |
Springer Berlin Heidelberg
2014
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| Subjects: | |
| Online Access: | http://irep.iium.edu.my/38537/ http://irep.iium.edu.my/38537/ http://irep.iium.edu.my/38537/ http://irep.iium.edu.my/38537/1/mardhiah_jurnal2.pdf http://irep.iium.edu.my/38537/4/WOS_Q1.pdf |
| Summary: | Background Female subjects with X-linked Alport syndrome have a single COL4A5 mutation, germ cell mosaicism in affected tissues and typically develop renal failure later or less often than male subjects. Women with two mutations are exceedingly rare, and usually have consanguineous parents or uniparental disomy. We describe here a 20-year-old woman who inherited two different COL4A5 variants, one from her father (c.2677G>C) and one from her mother (c.384 +1 G>A).
Case-diagnosis/treatment The index case had normal renal function, proteinuria and no clinically detectable hearing loss, or ocular abnormalities. Her father and paternal uncle devel- oped end-stage renal disease at 37 and 28 years respectively, together with hearing loss, but not lenticonus or central reti- nopathy. Her mother had mildly impaired renal function, proteinuria, hearing loss, but no ocular abnormalities. Her maternal grandfather and 22-year-old brother, both with this mutation, developed renal failure by 28 years with hearing loss, or had proteinuria and hearing loss respectively.
Conclusion The index case has clinical features consistent with germ cell mosaicism of two COL45A mutations associ- ated with adult-onset renal failure, but no ocular abnormali- ties. Her risk of renal failure is high, but the rate of progression to end-stage disease depends on the underlying mutations, and disease modification with renin–angiotensin blockade.
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