Top

Published in:

Open Access 01-12-2014 | Research article

A novel recessive mutation in the gene ELOVL4 causes a neuro-ichthyotic disorder with variable expressivity

Authors: Hina Mir, Syed Irfan Raza, Muhammad Touseef, Mazhar Mustafa Memon, Muhammad Nasim Khan, Sulman Jaffar, Wasim Ahmad

Published in: BMC Medical Genetics | Issue 1/2014

Abstract

Background

A rare neuro-ichthyotic disorder characterized by ichthyosis, spastic quadriplegia and intellectual disability and caused by recessive mutations in ELOVL4, encoding elongase-4 protein has recently been described. The objective of the study was to search for sequence variants in the gene ELOVL4 in three affected individuals of a consanguineous Pakistani family exhibiting features of neuro-ichthyotic disorder.

Methods

Linkage in the family was searched by genotyping microsatellite markers linked to the gene ELOVL4, mapped at chromosome 6p14.1. Exons and splice junction sites of the gene ELOVL4 were polymerase chain reaction amplified and sequenced in an automated DNA sequencer.

Results

DNA sequence analysis revealed a novel homozygous nonsense mutation (c.78C > G; p.Tyr26*).

Conclusions

Our report further confirms the recently described ELOVL4-related neuro-ichthyosis and shows that the neurological phenotype can be absent in some individuals.

Available only for authorised users

Leonard AE, Bobbi EG, Dorado J, Kroeger PE, Chuang LT, Thurmond JM, Parker-Barnes JM, Das T, Huang YS, Mukerji P: Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids. Biochem J. 2000, 350: 765-770. 10.1042/0264-6021:3500765.CrossRefPubMedPubMedCentral

Jakobsson A, Westerberg R, Jacobsson A: Fatty acid elongases in mammals: their regulation and roles in metabolism. Prog Lipid Res. 2006, 45: 237-249. 10.1016/j.plipres.2006.01.004.CrossRefPubMed

Tamura K, Makino A, Hullin-Matsuda F, Kobayashi T, Furihata M, Chung S, Ashida S, Miki T, Fujioka T, Shuin T, Nakamura Y, Nakagawa H: Novel lipogenic enzyme ELOVL7 is involved in prostate cancer growth through saturated long-chain fatty acid metabolism. Cancer Res. 2009, 69: 8133-8140. 10.1158/0008-5472.CAN-09-0775.CrossRefPubMed

Leonard AE, Pereira SL, Sprecher H, Huang YS: Elongation of long-chain fatty acids. Prog Lipid Res. 2004, 43: 36-54. 10.1016/S0163-7827(03)00040-7.CrossRefPubMed

Agbaga MP, Brush RS, Mandal MN, Henry K, Elliott MH, Anderson RE: Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of very long chain fatty acids. Proc Natl Acad Sci USA. 2008, 105: 12843-12848. 10.1073/pnas.0802607105.CrossRefPubMedPubMedCentral

Zhang K, Kniazeva M, Han M, Li W, Yu Z, Yang Z, Li Y, Metzker ML, Allikmets R, Zack DJ, Kakuk LE, Lagali PS, Wong PW, MacDonald IM, Sieving PA, Figueroa DJ, Austin CP, Gould RJ, Ayyagari R, Petrukhin K: A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy. Nat Genet. 2001, 27: 89-93.PubMed

Vasireddy V, Wong P, Ayyagari R: Genetics and molecular pathology of Stargardt-like macular degeneration. Prog Retin Eye Res. 2010, 29: 191-207. 10.1016/j.preteyeres.2010.01.001.CrossRefPubMedPubMedCentral

Aldahmesh MA, Mohamed JY, Alkuraya HS, Verma IC, Puri RD, Alaiya AA, Rizzo WB, Alkuraya FS: Recessive mutations in ELOVL4 cause ichthyosis, intellectual disability, and spastic quadriplegia. Am J Hum Genet. 2011, 89: 745-750. 10.1016/j.ajhg.2011.10.011.CrossRefPubMedPubMedCentral

Matise TC, Chen F, Chen W, De La Vega FM, Hansen M, He C, Hyland FC, Kennedy GC, Kong X, Murray SS, Ziegle JS, Stewart WC, Buyske S: A second-generation combined linkage physical map of the human genome. Genome Res. 2007, 17: 1783-1786. 10.1101/gr.7156307.CrossRefPubMedPubMedCentral

10.

Rozen S, Skaletsky H: Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol. 2000, 132: 365-386.PubMed

11.

Edwards AO, Donoso LA, Ritter R: A novel gene for autosomal dominant Stargardt-like macular dystrophy with homology to the SUR4 protein family. Invest Ophthalmol Vis Sci. 2001, 42: 2652-2663.PubMed

12.

Bernstein PS, Tammur J, Singh N, Hutchinson A, Dixon M, Pappas CM, Zabriskie NA, Zhang K, Petrukhin K, Leppert M, Allikmets R: Diverse macular dystrophy phenotype caused by a novel complex mutation in the ELOVL4 gene. Invest Ophthalmol Vis Sci. 2001, 42: 3331-3336.PubMed

13.

Maugeri A, Meire F, Hoyng CB, Vink C, Van Regemorter N, Karan G, Yang Z, Cremers FP, Zhang K: A novel mutation in the ELOVL4 gene causes autosomal dominant Stargardt-like macular dystrophy. Invest Ophthalmol Vis Sci. 2004, 45: 4263-4267. 10.1167/iovs.04-0078.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/15/25/prepub

Title: A novel recessive mutation in the gene ELOVL4 causes a neuro-ichthyotic disorder with variable expressivity
Authors: Hina Mir
Syed Irfan Raza
Muhammad Touseef
Mazhar Mustafa Memon
Muhammad Nasim Khan
Sulman Jaffar
Wasim Ahmad
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2014
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-15-25

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A novel recessive mutation in the gene ELOVL4 causes a neuro-ichthyotic disorder with variable expressivity

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2014

Segregation analysis in families with Charcot-Marie-Tooth disease allows reclassification of putative disease causing mutations

Diagnosis of Noonan syndrome and related disorders using target next generation sequencing

De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing

A systematic approach to the reporting of medically relevant findings from whole genome sequencing

Associations between speech features and phenotypic severity in Treacher Collins syndrome

Early onset of Chanarin-Dorfman syndrome with severe liver involvement in a patient with a complex rearrangement of ABHD5 promoter