Advertisement

Journal of Genetics

, Volume 96, Issue 2, pp 389–392 | Cite as

Mutation analysis of COL4A3 and COL4A4 genes in a Chinese autosomal-dominant Alport syndrome family

  • Liwei Guo
  • Duan Li
  • Shuangshuang Dong
  • Donghao Wang
  • Baosheng Yang
  • Yanmei HuangEmail author
Research Note

Abstract

Autosomal dominant Alport syndrome (ADAS) accounts for 5% of all cases of Alport syndrome (AS), a primary basement membrane disorder arising from mutations in genes encoding the type IV collagen protein family. Mutations in COL4A3 and COL4A4 genes were reported to be associated with ADAS. In this study, clinical data in a large consanguineous family with seven affected members were reviewed, and genomic DNA was extracted. For mutation screening, all exons of COL4A3 and COL4A4 genes were polymerase chain reaction-amplified and direct sequenced from genomic DNA, and the mutations were analyzed by comparing with members in this family, 100 ethnicity-matched controls and the sequence of COL4A3 and COL4A4 genes from GenBank. A novel mutation determining a nucleotide change was found, i.e. c.4195 A>T (p.Met1399Leu) at 44th exon of COL4A4 gene, and this mutation showed heterozygous in all patients of this family. Also a novel intron mutation (c.4127+11 C>T) was observed at COL4A4 gene. Thus the novel missense mutation c.4195 A>T (p.Met1399Leu) and the intron mutation (c.4127+11 C>T) at COL4A4 gene might be responsible for ADAS of this family. Our results broadened the spectrum of mutations in COL4A4 and had important implications in the diagnosis, prognosis, and genetic counselling of ADAS.

Keywords

autosomal-dominant Alport syndrome COL4A3  COL4A4 mutation detection 

Notes

Acknowledgements

Funding was provided by Scientific Research Foundation for Doctoal of Xinxiang Medical University (Grant No. 2015001), National Undergraduate Training Programs for Innovation and Entrepreneurship (Grant No. 201410472009), and Key Project of Henan Education Science during the 12th Five-Year Plan (Grant No. 2013-JKGHB-0035).

Supplementary material

12041_2017_786_MOESM1_ESM.pdf (371 kb)
Supplementary material 1 (pdf 372 KB)

References

  1. Boye E., Mollet G., Forestier L., Cohen-Solal L., Heidet L., Cochat P. et al. 1998 Determination of the genomic structure of the COL4A4 gene and of novel mutations causing autosomal recessive Alport syndrome. Am. J. Hum. Genet. 63, 1329–1340.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Ciccarese M., Casu D., Ki Wong F., Faedda R., Arvidsson S., Tonolo G. et al. 2001 Identification of a new mutation in the alpha4(IV) collagen gene in a family with autosomal dominant Alport syndrome and hypercholesterolaemia. Nephrol. Dial. Transplant. 16, 2008–2012.CrossRefPubMedGoogle Scholar
  3. Hertz J. M. 2009 Alport syndrome: molecular genetic aspects. Dan. Med. Bull. 56, 105–152.Google Scholar
  4. Jefferson J. A., Lemmink H. H., Hughes A. E., Hill C. M., Smeets H. J., Doherty C. C. et al.1997 Autosomal dominant Alport syndrome linked to the type IV collage alpha 3 and alpha 4 genes (COL4A3 and COL4A4). Nephrol. Dial. Transplant. 12, 1595–1599.CrossRefPubMedGoogle Scholar
  5. Kharrat M., Makni S., Makni K., Kammoun K., Charfeddine K., Azaeiz H. et al. 2006 Autosomal dominant Alport’s syndrome: study of a large Tunisian family. Saudi J. Kidney Dis. Transpl. 17, 320–325.PubMedGoogle Scholar
  6. Longo I., Porcedda P., Mari F., Giachino D., Meloni I., Deplano C. et al. 2002 COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome. Kidney Int. 61, 1947–1956.CrossRefPubMedGoogle Scholar
  7. Marcocci E., Uliana V., Bruttini M., Artuso R., Silengo M. C., Zerial M., et al. 2009 Autosomal dominant Alport syndrome: molecular analysis of the COL4A4 gene and clinical outcome. Nephrol. Dial. Transplant. 24, 1464–1471.Google Scholar
  8. Nabais Sa M. J., Storey H., Flinter F., Nagel M., Sampaio S., Castro R. et al. 2015 Collagen type IV-related nephropathies in Portugal: pathogenic COL4A3 and COL4A4 mutations and clinical characterization of 25 families. Clin. Genet. 88, 456–461.Google Scholar
  9. Papazachariou L., Demosthenous P., Pieri M., Papagregoriou G., Savva I., Stavrou C. et al. 2014 Frequency of COL4A3/COL4A4 mutations amongst families segregating glomerular microscopic hematuria and evidence for activation of the unfolded protein response: focal and segmental glomerulosclerosis is a frequent development during ageing. PLoS One 9, e115015.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Pescucci C., Mari F., Longo I., Vogiatzi P., Caselli R., Scala E. et al. 2004 Autosomal-dominant Alport syndrome: natural history of a disease due to COL4A3 or COL4A4 gene. Kidney Int. 65, 1598–1603.CrossRefPubMedGoogle Scholar
  11. Rosado C., Bueno E., Felipe C. and Gonzalez-Sarmiento R. 2014 COL4A4 gene study of a European population: description of new mutations causing autosomal dominant Alport syndrome. Int. J. Mol. Epidemiol. Genet. 5, 177–184.PubMedPubMedCentralGoogle Scholar
  12. Rosado C., Bueno E., Fraile P., Garcia-Cosmes P. and Gonzalez-Sarmiento R. 2015 A new mutation in the COL4A3 gene responsible for autosomal dominant Alport syndrome, which only generates hearing loss in some carriers. Eur. J. Med. Genet. 58, 35–38.CrossRefPubMedGoogle Scholar
  13. Savige J., Sheth S., Leys A., Nicholson A., Mack H. G. and Colville D. 2015 Ocular features in Alport syndrome: pathogenesis and clinical significance. Clin. J. Am. Soc. Nephrol. 10, 703–709.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Slajpah M., Gorinsek B., Berginc G., Vizjak A., Ferluga D., Hvala A. et al. 2007 Sixteen novel mutations identified in COL4A3, COL4A4, and COL4A5 genes in Slovenian families with Alport syndrome and benign familial hematuria. Kidney Int. 71, 1287–1295.CrossRefPubMedGoogle Scholar
  15. van der Loop F. T., Heidet L., Timmer E. D., van den Bosch B. J., Leinonen A., Antignac C. et al. 2000 Autosomal dominant Alport syndrome caused by a COL4A3 splice site mutation. Kidney Int. 58, 1870–1875.CrossRefPubMedGoogle Scholar

Copyright information

© Indian Academy of Sciences 2017

Authors and Affiliations

  1. 1.Department of Forensic Medicine, and Department of Basic MedicineXinxiang Medical UniversityXinxiangPeople’s Republic of China

Personalised recommendations