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Abstract: SA-PO559

Clinical and Genetic Features of Autosomal Dominant Alport Syndrome: A Cohort Study in China

Session Information

  • Genetic Diseases: Diagnosis
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Hu, Ningning, Shanghai Jiaotong University School of Medicine Xinhua Hospital, Shanghai, China
  • Xuantong, Dai, Shanghai Jiaotong University School of Medicine Xinhua Hospital, Shanghai, China
  • Lin, Fujun, Shanghai Jiaotong University School of Medicine Xinhua Hospital, Shanghai, China
  • Jiang, Gengru, Shanghai Jiaotong University School of Medicine Xinhua Hospital, Shanghai, China
Background

Patients carrying pathogenic heterozygous COL4A3 /COL4A4 mutations, considered to have autosomal dominant Alport syndrome (ADAS), account for nearly 1% of the population. ADAS patients show a wide spectrum of disease, extending from familial isolated microscopic hematuria to end-stage renal disease (ESRD). The aim of this study was to evaluate the clinical and genetic spectrum of Chinese ADAS patients.

Methods

106 families with ADAS referred from 11 Chinese hospitals between 2006 and 2022 were retrospectively studied. Clinical, genetic, laboratory, and pathological data were collected.

Results

Of the cohort of 221 patients, 66 (29.9%) patients were under the age of 18. Microhematuria was present in 98.2% patients, and extrarenal features were rare. 118 (53.4%) patients developed proteinuria [mean age 24.39±16.64 years], 58 (26.2%) with progression toward chronic kidney disease (CKD) 2 and more advanced CKD stages at a mean age of 41.07±13.62 years (22 required kidney replacement therapy at the mean age of 48.05±11.92 years). 49 patients underwent kidney biopsy: findings were consistent with classic Alport syndrome in 12 cases, with diffuse thin basement membrane in 12 cases and with focal segmental sclerosis in 10 cases. 90 pathogenic heterozygous COL4A3 /COL4A4 mutations were identified and 45 (50%) were Glycine substitution missense mutations. Genotype-phenotype correlation analysis only revealed a significant difference regarding progression toward CKD2 when comparing patients with Glycine mutation located in exons 1-20 and in exons 21 to carboxy terminus (P = 0.006).

Conclusion

Among Chinese patients carrying pathogenic heterozygous COL4A3 /COL4A4 mutations, a significant percentage is at risk for disease progression defined by the onset of proteinuria and renal function impairment. Thus, enhancing early diagnosis and timely intervention of ADAS must be considered to achieve optimal outcomes.

Funding

  • Government Support – Non-U.S.