Tags

Type your tag names separated by a space and hit enter

Next generation sequencing uncovers a missense mutation in COL4A1 as the cause of familial retinal arteriolar tortuosity.
Graefes Arch Clin Exp Ophthalmol 2014; 252(11):1789-94GA

Abstract

OBJECTIVES

Our aim was to determine the molecular cause of autosomal dominant familial retinal arteriolar tortuosity (FRAT) in a family with three affected subjects.

MATERIAL AND METHODS

Ophthalmologic evaluation included determination of best-corrected visual acuity (BCVA), slit-lamp and dilated fundus inspection, applanation tonometry, fundus photography, and fluorescein retinal angiography (FA). Molecular methods included whole exome sequencing analysis and Sanger sequencing validation of putative causal mutation in DNA from affected individuals.

RESULTS

Typical signs of familial retinal arteriolar tortuosity were observed in all three patients. Exome sequencing identified a heterozygous c.1528G > A (p. Gly510Arg) mutation in COL4A1. Sanger sequencing confirmed that all three patients harbored the same pathogenetic mutation in COL4A1. The p. Gly510Arg variant in COL4A1 was absent in DNA from an available unaffected daughter, from a set of control alleles, and from publicly available databases.

CONCLUSIONS

The molecular basis of familial retinal arteriolar tortuosity was identified for the first time, thus expanding the human phenotypes linked to COL4A1 mutations. Interestingly, the COL4A1 p.Gly510Arg mutation has been previously identified in a family with HANAC (Hereditary Angiopathy with Nephropathy, Aneurysm and Cramps), a multisystemic disease featuring retinal arteriolar tortuosity. No cerebral, neurologic, renal, cardiac or vascular anomalies were recognized in the pedigree described here. These data indicate that identical mutations in COL4A1 can originate both eye-restricted and systemic phenotypes.

Authors+Show Affiliations

Genetics Department and Research Unit, Institute of Ophthalmology "Conde de Valenciana" and Biochemistry Department, Faculty of Medicine, National Autonomous University of Mexico (UNAM), Chimalpopoca 14, Col. Obrera, Mexico City, CP, 06800, Mexico, jczenteno@institutodeoftalmologia.org.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25228067

Citation

Zenteno, Juan C., et al. "Next Generation Sequencing Uncovers a Missense Mutation in COL4A1 as the Cause of Familial Retinal Arteriolar Tortuosity." Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie, vol. 252, no. 11, 2014, pp. 1789-94.
Zenteno JC, Crespí J, Buentello-Volante B, et al. Next generation sequencing uncovers a missense mutation in COL4A1 as the cause of familial retinal arteriolar tortuosity. Graefes Arch Clin Exp Ophthalmol. 2014;252(11):1789-94.
Zenteno, J. C., Crespí, J., Buentello-Volante, B., Buil, J. A., Bassaganyas, F., Vela-Segarra, J. I., ... Marieges, M. T. (2014). Next generation sequencing uncovers a missense mutation in COL4A1 as the cause of familial retinal arteriolar tortuosity. Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie, 252(11), pp. 1789-94. doi:10.1007/s00417-014-2800-6.
Zenteno JC, et al. Next Generation Sequencing Uncovers a Missense Mutation in COL4A1 as the Cause of Familial Retinal Arteriolar Tortuosity. Graefes Arch Clin Exp Ophthalmol. 2014;252(11):1789-94. PubMed PMID: 25228067.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Next generation sequencing uncovers a missense mutation in COL4A1 as the cause of familial retinal arteriolar tortuosity. AU - Zenteno,Juan C, AU - Crespí,Jaume, AU - Buentello-Volante,Beatriz, AU - Buil,Jose A, AU - Bassaganyas,Francisca, AU - Vela-Segarra,Jose I, AU - Diaz-Cascajosa,Jesus, AU - Marieges,Maria T, Y1 - 2014/09/17/ PY - 2014/06/02/received PY - 2014/09/02/accepted PY - 2014/08/28/revised PY - 2014/9/18/entrez PY - 2014/9/18/pubmed PY - 2015/4/16/medline SP - 1789 EP - 94 JF - Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie JO - Graefes Arch. Clin. Exp. Ophthalmol. VL - 252 IS - 11 N2 - OBJECTIVES: Our aim was to determine the molecular cause of autosomal dominant familial retinal arteriolar tortuosity (FRAT) in a family with three affected subjects. MATERIAL AND METHODS: Ophthalmologic evaluation included determination of best-corrected visual acuity (BCVA), slit-lamp and dilated fundus inspection, applanation tonometry, fundus photography, and fluorescein retinal angiography (FA). Molecular methods included whole exome sequencing analysis and Sanger sequencing validation of putative causal mutation in DNA from affected individuals. RESULTS: Typical signs of familial retinal arteriolar tortuosity were observed in all three patients. Exome sequencing identified a heterozygous c.1528G > A (p. Gly510Arg) mutation in COL4A1. Sanger sequencing confirmed that all three patients harbored the same pathogenetic mutation in COL4A1. The p. Gly510Arg variant in COL4A1 was absent in DNA from an available unaffected daughter, from a set of control alleles, and from publicly available databases. CONCLUSIONS: The molecular basis of familial retinal arteriolar tortuosity was identified for the first time, thus expanding the human phenotypes linked to COL4A1 mutations. Interestingly, the COL4A1 p.Gly510Arg mutation has been previously identified in a family with HANAC (Hereditary Angiopathy with Nephropathy, Aneurysm and Cramps), a multisystemic disease featuring retinal arteriolar tortuosity. No cerebral, neurologic, renal, cardiac or vascular anomalies were recognized in the pedigree described here. These data indicate that identical mutations in COL4A1 can originate both eye-restricted and systemic phenotypes. SN - 1435-702X UR - https://www.unboundmedicine.com/medline/citation/25228067/Next_generation_sequencing_uncovers_a_missense_mutation_in_COL4A1_as_the_cause_of_familial_retinal_arteriolar_tortuosity_ L2 - https://dx.doi.org/10.1007/s00417-014-2800-6 DB - PRIME DP - Unbound Medicine ER -