Download PDF
Klin Monbl Augenheilkd 2016; 233(04): 475-477
DOI: 10.1055/s-0042-102585
Der interessante Fall
Georg Thieme Verlag KG Stuttgart · New York

Swiss Family with Dominant Stargardt Disease Caused by a Recurrent Mutation in the ELOVL4 Gene

Rekurrente ELOVL4 Genmutation verursacht dominante Stargardt-Krankheit in einer Schweizer Familie
H. V. Tran   *
1   Jules-Gonin Eye Hospital, Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland
,
E. Moret   *
2   IRO-Institute for Research in Ophthalmology, Sion, Switzerland
3   Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
,
V. Vaclavik
1   Jules-Gonin Eye Hospital, Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland
,
F. Marcelli
2   IRO-Institute for Research in Ophthalmology, Sion, Switzerland
,
M. M. Abitbol
4   Department of Ophthalmology of Necker-Enfants-Malades, University Hospital, Paris Descartes University, Paris, France
,
F. L. Munier
1   Jules-Gonin Eye Hospital, Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland
2   IRO-Institute for Research in Ophthalmology, Sion, Switzerland
3   Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
,
D. F. Schorderet
1   Jules-Gonin Eye Hospital, Department of Ophthalmology, University of Lausanne, Lausanne, Switzerland
2   IRO-Institute for Research in Ophthalmology, Sion, Switzerland
3   Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
5   EPFL-Ecole polytechnique fédérale de Lausanne, Lausanne, Switzerland
› Author Affiliations
Further Information

Publication History

Publication Date:
26 April 2016 (online)

Also available at
    Permissions and Reprints

Background

Stargardt (STGD) disease is responsible for 7 % of all retinal dystrophies and affects 1 in 10 000 people [1]. The typical onset occurs during the first two decades of life, which makes it the most common form of juvenile macular degeneration. It rapidly progresses and has a poor visual prognosis. STGD has been associated with considerable clinical and genetic heterogeneity. STGD can be classified into three variants based on the gene affected and is transmitted as an autosomal recessive or dominant disorder. Nearly two thirds of the cases, classified as STGD1, are caused by mutations in the ATP-binding cassette transporter, retina specific gene (ABCA4 on chromosome 1p21–22) and have predominantly autosomal recessive inheritance. The other one third of the cases has been linked to two different variants, the STGD3 and STGD4. STGD3 (OMIM 600 110) is associated with mutations in the elongation of very long chain fatty acids-like 4 gene (ELOVL4) on chromosome 6q16 [2], [3], [4]. It has an autosomal dominant inheritance whereas STGD4 is associated to mutations in the prominin 1 gene (PROM1) on chromosome 4. Mutations in ELOVL4 are rare and only 9 variants have been described so far (6 single nucleotide and 3 indel/del mutations) [2], [3], [5], [6], [7], [8], [9]. But from these mutations, only 4 are associated with STGD3. The others were identified in patients with neuro-ichthyotic disorders or age-related maculopathy. The purpose of this report is to describe the clinical and genetic study of a 2-generation family with dominant Stargardt disease due to ELOVL4 mutation.

* Both authors contributed equally to this work.


 

  • References

  • 1 Rotenstreich Y, Fishman GA, Anderson RJ. Visual acuity loss and clinical observations in a large series of patients with Stargardt disease. Ophthalmology 2003; 110: 1151-1158
    CrossrefPubMedGoogle Scholar
  • 2 Zhang K, Kniazeva M, Han M et al. A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy. Nat Genet 2001; 7: 89-93
    PubMedGoogle Scholar
  • 3 Maugeri A, Meire F, Hoyng CB et al. A novel mutation in the ELOVL4 gene causes autosomal dominant Stargardt-like macular dystrophy. Invest Ophthalmol Vis Sci 2004; 45: 4263-4267
    CrossrefPubMedGoogle Scholar
  • 4 Bernstein PS, Tammur J, Singh N et al. Diverse macular dystrophy phenotype caused by a novel complex mutation in the ELOVL4 gene. Invest Ophthalmol Vis Sci 2001; 42: 3331-3336
    PubMedGoogle Scholar
  • 5 Mir H, Raza SI, Touseef M et al. A novel recessive mutation in the gene ELOVL4 causes a neuro-ichthyotic disorder with variable expressivity. BMC Med Genet 2014; DOI: 10.1186/1471-2350-15-25. Advanced online publication Feb 26 DOI: 10.1186/1471-2350-15-25.
    PubMedGoogle Scholar
  • 6 Cadieux-Dion M, Turcotte-Gauthier M, Noreau A et al. Expanding the clinical phenotype associated with ELOVL4 mutation: study of a large French-Canadian family with autosomal dominant spinocerebellar ataxia and erythrokeratodermia. JAMA Neurol 2014; 71: 470-475
    CrossrefPubMedGoogle Scholar
  • 7 Aldahmesh MA, Mohamed JY, Alkuraya HS et al. Recessive mutations in ELOVL4 cause ichthyosis, intellectual disability, and spastic quadriplegia. Am J Hum Genet 2011; 89: 745-750
    CrossrefPubMedGoogle Scholar
  • 8 Conley YP1 Thalamuthu A, Jakobsdottir J. et al. Candidate gene analysis suggests a role for fatty acid biosynthesis and regulation of the complement system in the etiology of age-related maculopathy. Hum Mol Genet 2005; 14: 1991-2002
    CrossrefPubMedGoogle Scholar
  • 9 Strom SP1 Gao YQ, Martinez A. et al. Molecular diagnosis of putative Stargardt Disease probands by exome sequencing. BMC Med Genet 2012; 13: 67
    PubMedGoogle Scholar
  • 10 Schorderet DF, Iouranova A, Favez T et al. IROme, a new high-throughput molecular tool for the diagnosis of inherited retinal dystrophies. BioMed Research International Volume 2013; 2013: 198089
    PubMedGoogle Scholar
  • 11 Molday RS, Zhang K. Defective lipid transport and biosynthesis in recessive and dominant Stargardt macular degeneration. Prog Lipid Res 2010; 49: 476-492
    CrossrefPubMedGoogle Scholar
  • 12 Barabas P, Liu A, Xing W et al. Role of ELOVL4 and very long-chain polyunsaturated fatty acids in mouse models of Stargardt type 3 retinal degeneration. Proc Natl Acad Sci USA 2013; 110: 5181-5186
    CrossrefPubMedGoogle Scholar