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Clinical and genetic features in autosomal recessive and X-linked Alport syndrome

Abstract

Background

This study determined the family history and clinical features that suggested autosomal recessive rather than X-linked Alport syndrome.

Methods

All patients had the diagnosis of Alport syndrome and the mode of inheritance confirmed by genetic testing, and underwent examination at a single centre.

Results

Patients comprised 9 males and 6 females with autosomal recessive Alport syndrome, and 18 males and 22 females with X-linked disease. Fourteen (93 %) individuals with autosomal recessive Alport syndrome developed early end-stage renal failure, all 15 had hearing loss, and most had lenticonus (12, 80 %), and a central (13, 87 %) or peripheral (13, 87 %) retinopathy. These features occurred as often as in males with X-linked disease. Females with autosomal recessive inheritance were less likely to have an affected family member in another generation (p = 0.01) than females with X-linked disease. They were more likely to have renal failure (p = 0.003), hearing loss (p = 0.02) and lenticonus (p < 0.001). Fifty percent had a central retinopathy compared with 18 % with X-linked disease (p = 0.14), but peripheral retinopathy prevalence was not different (p = 0.64). Nonsense mutations accounted for 67 % (8/12) of these disease-causing mutations.

Conclusions

Autosomal recessive inheritance is increased in females with Alport syndrome and early onset renal failure, hearing loss, lenticonus, and, possibly, central retinopathy.

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Acknowledgements

We would like to thank the many patients and their families who took part in these studies. This work was funded in part by the Alport Foundation of Australia.

Conflict of interest statement

None.

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Corresponding author

Correspondence to Judy Savige.

Additional information

This work was presented as a poster at the American Society of Nephrology meeting in San Diego in October 2012. The mutations in these patients have been described in a separate publication.

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Wang, Y., Sivakumar, V., Mohammad, M. et al. Clinical and genetic features in autosomal recessive and X-linked Alport syndrome. Pediatr Nephrol 29, 391–396 (2014). https://doi.org/10.1007/s00467-013-2643-0

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  • DOI: https://doi.org/10.1007/s00467-013-2643-0

Keywords

  • Alport syndrome
  • Retinopathy
  • Nonsense mutations