Autosomal recessive Alport syndrome caused by a novel COL4A4 splice site mutation: a case report
| Autor: | Tamara Nikuševa Martić, Slaven Abdović, Matija Horaček, Martin Ćuk, Maja Oroz, Marija Šenjug Perica, Petar Šenjug, Danica Galešić Ljubanović |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Pathology
medicine.medical_specialty Splice site mutation medicine.diagnostic_test Genetic heterogeneity business.industry Genetic counseling Case Report General Medicine urologic and male genital diseases medicine.disease Compound heterozygosity 03 medical and health sciences 0302 clinical medicine medicine Sensorineural hearing loss Alport syndrome next generation sequencing 030212 general & internal medicine Megalencephaly business Genetic testing |
| Zdroj: | Croatian Medical Journal |
| ISSN: | 1332-8166 0353-9504 |
| Popis: | Alport syndrome (AS) is a genetically heterogenic, structural disorder of the glomerular basement membrane (GBM) due to the mutation of COL4A3, COL4A4, or COL4A5 genes, which clinically presents as progressive hematuric nephritis with ultrastructural changes of the GBM, high tone sensorineural hearing loss, and ocular lesions. About 15% of AS cases have autosomal mutations of COL4A3 and COL4A4 genes, including homozygous and compound heterozygous mutations. Here, we present a case of a two-year-old boy with autosomal recessive Alport syndrome (ARAS) caused by a novel c.193-2A>C COL4A4 mutation. The patient had a delayed motor and sensory development coupled with speech and language delay, megalencephaly, hematuria and proteinuria, and normal tonal audiogram and ophthalmology exam. Extensive genetic, metabolic, and neurologic workup performed at the age of 10 months was unremarkable and patient's megalencephaly was described as familial benign megalencephaly. Kidney biopsy analysis showed characteristic signs of AS. Mutations screening with use of Illumina MiSeq platform revealed that the patient was homozygous for a newly discovered splice acceptor pathogenic variant c.193-2A>C found in COL4A4 at the genomic position chr2:227985866 and both parents were heterozygous carriers. The genetic heterogeneity of AS makes the diagnostic process challenging. Although renal biopsy provides information about the characteristic GBM changes and the degree of renal parenchyma damage (interstitial fibrosis and tubular atrophy ratio), genetic testing is a more sensitive and specific method that also gives insight into potential disease severity and clinical course, and provides the basis for genetic counseling. |
| Databáze: | OpenAIRE |
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