Kidney Week

Abstract: SA-PO574

A Rare Kidney Disease Family with CCDC114 Mutation and Cilia

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

Author

• Chen, Xiangmei, PLA Genaral Hospital, Beijing, Beijing, China

Xiangmei Chen,

Background

Ciliopathies is a group of diseases characteriaed by dysfunction of cilia and patients with ciliapathies have a variety of developmental and degenerative disorders.

Methods

We present the case of a 15-year-old child with dysplasia and multiple organ damage who was initially diagnosed as nephrotic syndrome.Her parents and sister are in good health.Physical examination shows normal blood pressure;edema of face and lower limb;sensorineural deafness and hypopsia.She also has dysplasia including congenital heart disease and duplex kidney.The patient also has intermittent cough.Laboratory investigation shows creatinine is 1.88 mg/dl;eGFR is 39.12 mL/min/1.73 m²;proteinuria is 3.42g/24h;albumin is 23.1g/L;hemoglobin is 88g/L;decreased thyroid function. The brain MRI shows abnormal signal in bilateral parietal lobe of the brain groove in FLAIR sequence which indicates decreased cerebrospinal fluid flow rate. Renal biopsy shows focal segmental glomerular sclerosis. The patient progressed to renal failure and received hemodialysis 10 months after renal biopsy. The patient’s clinical manifestations are consistent with cilioapathies, very similar to Alström syndrome. Cilia immunofluorescence of renal tissue showed a decrease number of cilium of the patient compared to normal kidney.Then WES shows a site mutation in CCDC114(NM_144577 exon7 c.596C＞T p.Ala199Val)in patient. We found that CCDC114 located in centrosome and knock down CCDC114 could affect the occurrence of cilia in hRPE1 cells.

Conclusion

We found a decrease in the number of cilium in the kidney of patient with ciliapathies and identified CCDC114 as the main target gene by WES. We found that CCDC114 affected primary cilia formation in hRPE1 cells.

Genotype of the family

Funding

• Government Support - Non-U.S.