Skip to main content
Erschienen in: Pediatric Nephrology 3/2014

01.03.2014 | Brief Report

A female with X-linked Alport syndrome and compound heterozygous COL4A5 mutations

verfasst von: Mardhiah Mohammad, Ranjit Nanra, Deb Colville, Paul Trevillian, Yanyan Wang, Helen Storey, Frances Flinter, Judy Savige

Erschienen in: Pediatric Nephrology | Ausgabe 3/2014

Einloggen, um Zugang zu erhalten

Abstract

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 developed end-stage renal disease at 37 and 28 years respectively, together with hearing loss, but not lenticonus or central retinopathy. 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 associated with adult-onset renal failure, but no ocular abnormalities. 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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Govan JA (1983) Ocular manifestations of Alport’s syndrome: a hereditary disorder of basement membranes? Br J Ophthalmol 67:493–503PubMedCrossRef Govan JA (1983) Ocular manifestations of Alport’s syndrome: a hereditary disorder of basement membranes? Br J Ophthalmol 67:493–503PubMedCrossRef
2.
Zurück zum Zitat Usui T, Ichibe M, Hasegawa S, Miki A, Baba E, Tanimoto N, Abe H (2004) Symmetrical reduced retinal thickness in a patient with Alport syndrome. Retina 24:977–979PubMedCrossRef Usui T, Ichibe M, Hasegawa S, Miki A, Baba E, Tanimoto N, Abe H (2004) Symmetrical reduced retinal thickness in a patient with Alport syndrome. Retina 24:977–979PubMedCrossRef
3.
Zurück zum Zitat Shaw EA, Colville D, Wang YY, Zhang KW, Dagher H, Fassett R, Guymer R, Savige J (2007) Characterization of the peripheral retinopathy in X-linked and autosomal recessive Alport syndrome. Nephrol Dial Transplant 22:104–108PubMedCrossRef Shaw EA, Colville D, Wang YY, Zhang KW, Dagher H, Fassett R, Guymer R, Savige J (2007) Characterization of the peripheral retinopathy in X-linked and autosomal recessive Alport syndrome. Nephrol Dial Transplant 22:104–108PubMedCrossRef
4.
Zurück zum Zitat Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer KO, Flinter F, Pirson Y, Dahan K, Wieslander J, Persson U, Tryggvason K, Martin P, Hertz JM, Schroder C, Sanak M, Carvalho MF, Saus J, Antignac C, Smeets H, Gubler MC (2003) X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: a “European Community Alport Syndrome Concerted Action” study. J Am Soc Nephrol 14:2603–2610PubMedCrossRef Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer KO, Flinter F, Pirson Y, Dahan K, Wieslander J, Persson U, Tryggvason K, Martin P, Hertz JM, Schroder C, Sanak M, Carvalho MF, Saus J, Antignac C, Smeets H, Gubler MC (2003) X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: a “European Community Alport Syndrome Concerted Action” study. J Am Soc Nephrol 14:2603–2610PubMedCrossRef
5.
Zurück zum Zitat Dagher H, Buzza M, Colville D, Jones C, Powell H, Fassett R, Wilson D, Agar J, Savige J (2001) A comparison of the clinical, histopathologic, and ultrastructural phenotypes in carriers of X-linked and autosomal recessive Alport’s syndrome. Am J Kidney Dis 38:1217–1228PubMedCrossRef Dagher H, Buzza M, Colville D, Jones C, Powell H, Fassett R, Wilson D, Agar J, Savige J (2001) A comparison of the clinical, histopathologic, and ultrastructural phenotypes in carriers of X-linked and autosomal recessive Alport’s syndrome. Am J Kidney Dis 38:1217–1228PubMedCrossRef
6.
Zurück zum Zitat Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer KO, Flinter F, Pirson Y, Verellen C, Wieslander J, Persson U, Tryggvason K, Martin P, Hertz JM, Schroder C, Sanak M, Krejcova S, Carvalho MF, Saus J, Antignac C, Smeets H, Gubler MC (2000) X-linked Alport syndrome: natural history in 195 families and genotype- phenotype correlations in males. J Am Soc Nephrol 11:649–657PubMed Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer KO, Flinter F, Pirson Y, Verellen C, Wieslander J, Persson U, Tryggvason K, Martin P, Hertz JM, Schroder C, Sanak M, Krejcova S, Carvalho MF, Saus J, Antignac C, Smeets H, Gubler MC (2000) X-linked Alport syndrome: natural history in 195 families and genotype- phenotype correlations in males. J Am Soc Nephrol 11:649–657PubMed
7.
Zurück zum Zitat Gross O, Netzer KO, Lambrecht R, Seibold S, Weber M (2002) Meta-analysis of genotype-phenotype correlation in X-linked Alport syndrome: impact on clinical counselling. Nephrol Dial Transplant 17:1218–1227PubMedCrossRef Gross O, Netzer KO, Lambrecht R, Seibold S, Weber M (2002) Meta-analysis of genotype-phenotype correlation in X-linked Alport syndrome: impact on clinical counselling. Nephrol Dial Transplant 17:1218–1227PubMedCrossRef
8.
Zurück zum Zitat Tan R, Colville D, Wang YY, Rigby L, Savige J (2010) Alport retinopathy results from “severe” COL4A5 mutations and predicts early renal failure. Clin J Am Soc Nephrol 5:34–38PubMedCrossRef Tan R, Colville D, Wang YY, Rigby L, Savige J (2010) Alport retinopathy results from “severe” COL4A5 mutations and predicts early renal failure. Clin J Am Soc Nephrol 5:34–38PubMedCrossRef
9.
Zurück zum Zitat Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F (2013) Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. J Am Soc Nephrol 24:364–375PubMedCrossRef Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F (2013) Expert guidelines for the management of Alport syndrome and thin basement membrane nephropathy. J Am Soc Nephrol 24:364–375PubMedCrossRef
10.
Zurück zum Zitat Persikov AV, Pillitteri RJ, Amin P, Schwarze U, Byers PH, Brodsky B (2004) Stability related bias in residues replacing glycines within the collagen triple helix (Gly-Xaa-Yaa) in inherited connective tissue disorders. Hum Mutat 24:330–337PubMedCrossRef Persikov AV, Pillitteri RJ, Amin P, Schwarze U, Byers PH, Brodsky B (2004) Stability related bias in residues replacing glycines within the collagen triple helix (Gly-Xaa-Yaa) in inherited connective tissue disorders. Hum Mutat 24:330–337PubMedCrossRef
11.
Zurück zum Zitat Mete UO, Karaaslan C, Ozbilgin MK, Polat S, Tap O, Kaya M (1996) Alport’s syndrome with bilateral macular hole. Acta Ophthalmol Scand 74:77–80PubMedCrossRef Mete UO, Karaaslan C, Ozbilgin MK, Polat S, Tap O, Kaya M (1996) Alport’s syndrome with bilateral macular hole. Acta Ophthalmol Scand 74:77–80PubMedCrossRef
12.
Zurück zum Zitat Gross O, Licht C, Anders HJ, Hoppe B, Beck B, Tonshoff B, Hocker B, Wygoda S, Ehrich JH, Pape L, Konrad M, Rascher W, Dotsch J, Muller-Wiefel DE, Hoyer P, Knebelmann B, Pirson Y, Grunfeld JP, Niaudet P, Cochat P, Heidet L, Lebbah S, Torra R, Friede T, Lange K, Muller GA, Weber M (2012) Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int 81:494–501PubMedCrossRef Gross O, Licht C, Anders HJ, Hoppe B, Beck B, Tonshoff B, Hocker B, Wygoda S, Ehrich JH, Pape L, Konrad M, Rascher W, Dotsch J, Muller-Wiefel DE, Hoyer P, Knebelmann B, Pirson Y, Grunfeld JP, Niaudet P, Cochat P, Heidet L, Lebbah S, Torra R, Friede T, Lange K, Muller GA, Weber M (2012) Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int 81:494–501PubMedCrossRef
13.
Zurück zum Zitat Mochizuki T, Lemmink HH, Mariyama M, Antignac C, Gubler MC, Pirson Y, Verellen-Dumoulin C, Chan B, Schroder CH, Smeets HJ, Reeders ST (1994) Identification of mutations in the alpha 3(IV) and alpha 4(IV) collagen genes in autosomal recessive Alport syndrome. Nat Genet 8:77–81PubMedCrossRef Mochizuki T, Lemmink HH, Mariyama M, Antignac C, Gubler MC, Pirson Y, Verellen-Dumoulin C, Chan B, Schroder CH, Smeets HJ, Reeders ST (1994) Identification of mutations in the alpha 3(IV) and alpha 4(IV) collagen genes in autosomal recessive Alport syndrome. Nat Genet 8:77–81PubMedCrossRef
14.
Zurück zum Zitat Fujii K, Minami N, Hayashi Y, Nishino I, Nonaka I, Tanabe Y, Takanashi J, Kohno Y (2009) Homozygous female Becker muscular dystrophy. Am J Med Genet 149A:1052–1055PubMedCrossRef Fujii K, Minami N, Hayashi Y, Nishino I, Nonaka I, Tanabe Y, Takanashi J, Kohno Y (2009) Homozygous female Becker muscular dystrophy. Am J Med Genet 149A:1052–1055PubMedCrossRef
15.
Zurück zum Zitat Temme J, Peters F, Lange K, Pirson Y, Heidet L, Torra R, Grunfeld JP, Weber M, Licht C, Muller GA, Gross O (2012) Incidence of renal failure and nephroprotection by RAAS inhibition in heterozygous carriers of X-chromosomal and autosomal recessive Alport mutations. Kidney Int 81:779–783PubMedCrossRef Temme J, Peters F, Lange K, Pirson Y, Heidet L, Torra R, Grunfeld JP, Weber M, Licht C, Muller GA, Gross O (2012) Incidence of renal failure and nephroprotection by RAAS inhibition in heterozygous carriers of X-chromosomal and autosomal recessive Alport mutations. Kidney Int 81:779–783PubMedCrossRef
Metadaten
Titel
A female with X-linked Alport syndrome and compound heterozygous COL4A5 mutations
verfasst von
Mardhiah Mohammad
Ranjit Nanra
Deb Colville
Paul Trevillian
Yanyan Wang
Helen Storey
Frances Flinter
Judy Savige
Publikationsdatum
01.03.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 3/2014
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-013-2682-6

Weitere Artikel der Ausgabe 3/2014

Pediatric Nephrology 3/2014 Zur Ausgabe

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.