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Women and Alport syndrome

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Abstract

X-linked Alport syndrome (XLAS) is caused by mutations in type IV collagen causing sensorineural hearing loss, eye abnormalities, and progressive kidney dysfunction that results in near universal end-stage renal disease (ESRD) and the need for kidney transplantation in affected males. Until recent decades, the disease burden in heterozygous “carrier” females was largely minimized or ignored. Heterozygous females have widely variable disease outcomes, with some affected females exhibiting normal urinalysis and kidney function, while others develop ESRD and deafness. While the determinants of disease severity in females with XLAS are uncertain, skewing of X-chromosome inactivation has recently been found to play a role. This review will explore the natural history of heterozygous XLAS females, the determinants of disease severity, and the utility of using XLAS females as kidney donors.

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Acknowledgments

Thank you to Dr. Clifford Kashtan for helpful comments on the manuscript and Dr. Yoav Segal for providing images of the heterozygous XLAS mouse.

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Minnesota Amplatz Children’s Hospital, Minneapolis, MN, USA

    Michelle N. Rheault

  2. Division of Pediatric Nephrology, University of Minnesota, 420 Delaware St. SE, MMC 491, Minneapolis, MN, 55455, USA

    Michelle N. Rheault

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  1. Michelle N. Rheault
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Correspondence to Michelle N. Rheault.

Additional information

Answers

1) b

2) e

3) a

4) e

5) d

6) b

Review Questions (answers are given following the references)

Review Questions (answers are given following the references)

  1. 1.

    The percentage of Alport syndrome inherited in an X-linked manner is:

    1. a.

      100%

    2. b.

      80%

    3. c.

      50%

    4. d.

      20%

  2. 2.

    Heterozygous XLAS females can present with:

    1. a.

      Normal urinalysis

    2. b.

      Microscopic hematuria

    3. c.

      Proteinuria

    4. d.

      Sensorineural hearing loss

    5. e.

      All of the above

  3. 3.

    The following has been shown to influence disease outcome in XLAS heterozygous females

    1. a.

      X inactivation

    2. b.

      Ethnicity

    3. c.

      ACE inhibition

    4. d.

      Pregnancy

    5. e.

      Genotype

  4. 4.

    Which of the following are risk factors for renal disease progression in XLAS heterozygous females?

    1. a.

      Microscopic hematuria

    2. b.

      Proteinuria

    3. c.

      Use of hormone replacement therapy

    4. d.

      Hearing loss

    5. e.

      B and D

    6. f.

      B and C

  5. 5.

    X inactivation patterns in this tissue can predict X inactivation patterns in the kidney

    1. a.

      Blood lymphocytes

    2. b.

      Skin

    3. c.

      Urinary epithelium

    4. d.

      None of the above

  6. 6.

    Heterozygous XLAS females should be considered as kidney donors if they meet all of the following criteria except:

    1. a.

      Presence of microscopic hematuria

    2. b.

      Presence of proteinuria

    3. c.

      Absence of sensorineural hearing loss

    4. d.

      Absence of hypertension

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Rheault, M.N. Women and Alport syndrome. Pediatr Nephrol 27, 41–46 (2012). https://doi.org/10.1007/s00467-011-1836-7

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  • DOI: https://doi.org/10.1007/s00467-011-1836-7

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