Abstract: PO1665
Phenotype Characteristics of Patients with Novel and Described COL4A5 Mutations Causing X-Linked Alport Syndrome in Croatian Population
Session Information
- Genetic Diseases of the Kidneys: Non-Cystic - 2
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1002 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Ljubanovic, Danica Galesic, University Hospital Dubrava, Zagreb, Croatia
- Horacek, Matija, School of Medicine, University of Zagreb, Zagreb, Croatia
- Senjug, Petar, University Hospital Dubrava, Zagreb, Croatia
- Nikuseva-Martic, Tamara, School of Medicine, University of Zagreb, Zagreb, Croatia
- Senjug Perica, Marija, Children's Hospital Srebrnjak, Zagreb, Croatia
- Oroz, Maja, School of Medicine, University of Zagreb, Zagreb, Croatia
- Klaric, Dragan, Zadar General Hospital, Zadar, Croatia
- Horvatic, Ivica, University Hospital Dubrava, Zagreb, Croatia
- Milosevic, Danko, University Hospital Centre Zagreb, Zagreb, Croatia
- Batinic, Danica, Children's Hospital Srebrnjak, Zagreb, Croatia
- Galesic, Kresimir, University Hospital Dubrava, Zagreb, Croatia
Background
Alport syndrome (AS) is an inherited renal disorder caused by mutations in collagen IV genes. The most common type is X-linked AS caused by COL4A5 mutations which presents as a progressive nephritis with hematuria, ultrastructural changes of glomerular basement membrane, sensorineural hearing loss and ocular lesions. Males are usually more severely affected.
Methods
We are presenting genotype-phenotype correlation for Croatian patients with X-linked AS. Next generation sequencing for COL4A3, COL4A4 and COL4A5 was performed as part of the nationwide project "Genotype-phenotype correlation in Alport syndrome and thin basement membrane nephropathy (TBMN)“. There were 24 male and 26 female patients from 36 unrelated families. Probands were selected based on the kidney biopsy findings.
Results
We have identified 23 mutations, 13 being novel and 10 previously reported. In two patients additional COL4A4 mutations were found. Male patients, median age 27 years, presented with hematuria (96%), proteinuria (54%), sensorineural hearing loss (27%) and ocular changes (4.5%). Most patients (62%) had normal, 17% mildly and 21% moderately reduced kidney function. No one had severe renal insufficiency or ESRD. Kidney biopsy was performed in 18 male patients and AS was the most common diagnosis (67%) followed by TBMN with FSGS (17%) and isolated TBMN (11%). In one patient (5%) the diagnosis was inconclusive for AS or TBMN. Female patients, median age 16 years, presented with hematuria (89%) and proteinuria (19 %). There were no ocular abnormalities and the hearing loss was present in 5% of patients. Most females (73%) had normal kidney function while 8% had mild, 12% moderate, 3.5% severe reduction of renal function and 3.5% had ESRD. The kidney biopsy was performed in 14 female patients. The most common diagnosis was AS (65%) followed by isolated TBMN (21%) and TBMN with FSGS (7%). Only 1 specimen (7%) was signed out as inconclusive for AS or TBMN.
Conclusion
We have presented characteristics of 50 Croatian patients with X-linked AS. In our cohort 56% of mutations were novel. While renal biopsy provides information about degree and the type of renal parenchyma damage, genetic analysis is crucial for diagnosis.
Funding
- Government Support - Non-U.S.