Kidney Week

Abstract: SA-PO603

Analysis of 24 Genes Reveals a Monogenic Cause in 11% of Cases with Steroid Resistant Nephrotic Syndrome at a Single Center

Session Information

• Noncystic Mendelian Diseases
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Genetic Diseases of the Kidney

• 802 Non-Cystic Mendelian Diseases

Authors

• Tan, Weizhen, Boston Children's Hospital, Boston, Massachusetts, United States

Weizhen Tan,

• Lovric, Svjetlana, Boston Children's Hospital, Boston, United States

Svjetlana Lovric,

• Ashraf, Shazia, Boston Children's Hospital, Boston, Massachusetts, United States

Shazia Ashraf,

• Rao, Jia, Boston Children's Hospital, Boston, Massachusetts, United States

Jia Rao,

• Schapiro, David, Boston Children's Hospital, Boston, Massachusetts, United States

David Schapiro,

• Airik, Merlin, Boston Children's Hospital, Boston, Massachusetts, United States

Merlin Airik,

• Shril, Shirlee, Boston Children's Hospital, Boston, Massachusetts, United States

Shirlee Shril,

• Gee, Heon Yung, Boston Children's Hospital, Boston, Massachusetts, United States

Heon Yung Gee,

• Baum, Michelle Amy, Boston Children's Hospital, Boston, Massachusetts, United States

Michelle Amy Baum,

• Daouk, Ghaleb H., Boston Children's Hospital, Boston, Massachusetts, United States

Ghaleb H. Daouk,

• Ferguson, Michael A., Boston Children's Hospital, Boston, Massachusetts, United States

Michael A. Ferguson,

• Rodig, Nancy MacDonald, Boston Children's Hospital, Boston, Massachusetts, United States

Nancy MacDonald Rodig,

• Somers, Michael J., Boston Children's Hospital, Boston, Massachusetts, United States

Michael J. Somers,

• Stein, Deborah R., Boston Children's Hospital, Boston, Massachusetts, United States

Deborah R. Stein,

• Vivante, Asaf, Boston Children's Hospital, Boston, Massachusetts, United States

Asaf Vivante,

• Warejko, Jillian Kateri, Boston Children's Hospital, Boston, Massachusetts, United States

Jillian Kateri Warejko,

• Widmeier, Eugen, Boston Children's Hospital, Boston, Massachusetts, United States

Eugen Widmeier,

• Hildebrandt, Friedhelm, Boston Children's Hospital, Boston, Massachusetts, United States

Friedhelm Hildebrandt,

Background

Background: Steroid resistant nephrotic syndrome (SRNS) is the second most frequent cause of end stage renal disease (ESRD) among patients manifesting <25 years of age. We performed mutation analysis using a high-throughput PCR-based microfluidic technology in 24 single-gene causes of SRNS in a cohort of 72 families, who manifested with steroid resistant nephrotic syndrome before the age of 25 years.

Methods

Methods: Within an 18 month interval, we obtained DNA samples, pedigree information, and clinical information from 77 consecutive children with SRNS from 72 different families seen at Boston Children’s Hospital (BCH). Mutation analysis was completed by combining high-throughput multiplex PCR with next-generation exon sequencing. We analyzed the sequences of 18 recessive and 6 dominant genes of SRNS in all 72 families for disease causing variants.

Results

Results: We identified the disease causing mutation in 8 of 72 (11.1%) families. Mutations were detected in the 6 genes: NPHS1 (2/72), WT1 (2/72), and in NPHS2, MYO1E, TRPC6, and INF2.
Median age of onset was 4.1 years in patients without a mutation (range 0.5-18.8), and 3.2 years in those where the causative mutation was detected (range 0.1-14.3). Mutations in dominant genes presented with a median onset of 4.5 years (range 3.2-14.3). Mutations in recessive genes presented with a median onset of 0.5 years (range 0.1-3.2).

Conclusion

Conclusion: Our molecular genetic diagnostic study identified the underlying monogenic cause of steroid-resistant nephrotic syndrome in ~11% of patients with SRNS using a cost effective technique. We delineated some of the therapeutic, diagnostic, or prognostic implications. Our study confirms that genetic testing is indicated in pediatric patients with SRNS.

Funding

• NIDDK Support