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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2017

Open Access 01-12-2017 | Research article

A novel NHS mutation causes Nance-Horan Syndrome in a Chinese family

Authors: Qi Tian, Yunping Li, Rizwana Kousar, Hui Guo, Fenglan Peng, Yu Zheng, Xiaohua Yang, Zhigao Long, Runyi Tian, Kun Xia, Haiying Lin, Qian Pan

Published in: BMC Medical Genetics | Issue 1/2017

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Abstract

Background

Nance-Horan Syndrome (NHS) (OMIM: 302350) is a rare X-linked developmental disorder characterized by bilateral congenital cataracts, with occasional dental anomalies, characteristic dysmorphic features, brachymetacarpia and mental retardation. Carrier females exhibit similar manifestations that are less severe than in affected males.

Methods

Here, we report a four-generation Chinese family with multiple affected individuals presenting Nance-Horan Syndrome. Whole-exome sequencing combined with RT-PCR and Sanger sequencing was used to search for a genetic cause underlying the disease phenotype.

Results

Whole-exome sequencing identified in all affected individuals of the family a novel donor splicing site mutation (NM_198270: c.1045 + 2T > A) in intron 4 of the gene NHS, which maps to chromosome Xp22.13. The identified mutation results in an RNA processing defect causing a 416-nucleotide addition to exon 4 of the mRNA transcript, likely producing a truncated NHS protein.

Conclusions

The donor splicing site mutation NM_198270: c.1045 + 2T > A of the NHS gene is the causative mutation in this Nance-Horan Syndrome family. This research broadens the spectrum of NHS gene mutations, contributing to our understanding of the molecular genetics of NHS.
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Literature
1.
2.
Bixler D, Higgins M, Hartsfield Jr J. The Nance-Horan syndrome: a rare X-linked ocular-dental trait with expression in heterozygous females. Clin Genet. 1984;26:30–5.CrossRefPubMed
3.
Nance EW, Warburg N, Bixler D, Helveston EM. Congenital X-linked cataracts, dental anomalies and brachymetacarpalia. Birth Defects Orig Artic Ser X. 1974;4:285–95.
4.
HORAN BM, Billson FA. X-linked cataract and hutchinsonian teeth. Aust Paediatr J. 1974;10:98–102.
5.
Tug E, Dilek NF, Javadiyan S, Burdon KP, Percin FE. A Turkish family with Nance-Horan Syndrome due to a novel mutation. Gene. 2013;525(1):141–5.CrossRefPubMed
6.
7.
Burdon KP, McKay JD, Sale MM, Russell-Eggitt IM, Mackey DA, Wirth MG, Elder JE, Nicoll A, Clarke MP, FitzGerald LM, et al. Mutations in a novel gene, NHS, cause the pleiotropic effects of Nance-Horan syndrome, including severe congenital cataract, dental anomalies, and mental retardation. Am J Hum Genet. 2003;73(5):1120–30.CrossRefPubMedPubMedCentral
8.
Hong N, Chen YH, Xie C, Xu BS, Huang H, Li X, Yang YQ, Huang YP, Deng JL, Qi M, et al. Identification of a novel mutation in a Chinese family with Nance-Horan syndrome by whole exome sequencing. J Zhejiang Univ Sci B. 2014;15(8):727–34.CrossRefPubMedPubMedCentral
9.
Brooks SP, Coccia M, Tang HR, Kanuga N, Machesky LM, Bailly M, Cheetham ME, Hardcastle AJ. The Nance-Horan syndrome protein encodes a functional WAVE homology domain (WHD) and is important for co-ordinating actin remodelling and maintaining cell morphology. Hum Mol Genet. 2010;19:2421–32.CrossRefPubMedPubMedCentral
10.
Coccia M, Brooks SP, Webb TR, Christodoulou K, Wozniak IO, Murday V, Balicki M, Yee HA, Wangensteen T, Riise R, et al. X-linked cataract and Nance-Horan syndrome are allelic disorders. Hum Mol Genet. 2009;18(14):2643–55.CrossRefPubMedPubMedCentral
11.
Li A, Li B, Wu L, Yang L, Chen N, Ma Z. Identification of a novel NHS mutation in a Chinese family with Nance-Horan Syndrome. Curr Eye Res. 2015;40(4):434–8.CrossRefPubMed
12.
Sun W, Xiao X, Li S, Guo X, Zhang Q. Exome sequencing of 18 Chinese families with congenital cataracts: a new sight of the NHS gene. PLoS One. 2014;9(6):e100455.CrossRefPubMedPubMedCentral
13.
Sharma S, Burdon KP, Dave A, Jamieson RV, Yaron Y, Billson F, Maldergem LV, Lorenz B, Gecz J, Craig JE. Novel causative mutations in patients with Nance-Horan syndrome and altered localization of the mutant NHS-A protein isoform. Mol Vision. 2008;14:1856–64.
14.
Huang KM, Wu J, Brooks SP, Hardcastle AJ, Lewis RA, Stambolian D. Identification of three novel NHS mutations in families with Nance-Horan syndrome. Mol Vis. 2007;13:470–4.PubMedPubMedCentral
15.
Florijn RJ, Loves W, de Buy Wenniger-Prick LJ M, Mannens MM, Tijmes N, Brooks SP, Hardcastle AJ, Bergen AA. New mutations in the NHS gene in Nance-Horan Syndrome families from the Netherlands. Eur J Hum Genet. 2006;14:986–90.CrossRefPubMed
16.
Guo H, Tong P, Peng Y, Wang T, Liu Y, Chen J, Li Y, Tian Q, Hu Y, Zheng Y, et al. Homozygous loss-of-function mutation of the LEPREL1 gene causes severe non-syndromic high myopia with early-onset cataract. Clin Genet. 2014;86(6):575–9.CrossRefPubMed
17.
Ramprasad VL, Thool A, Murugan S, Nancarrow D, Vyas P, Rao SK, Vidhya A, Ravishankar K, Kumaramanickavel G. Truncating mutation in the NHS gene: phenotypic heterogeneity of Nance-Horan syndrome in an asian Indian family. Invest Ophthalmol Vis Sci. 2005;46(1):17–23.CrossRefPubMed
18.
Lewis RA, Nussbaum RL, Stambolian D. Mapping X-linked ophthalmic diseases. IV. Provisional assignment of the locus for X-linked congenital cataracts and microcornea (the Nance-Horan syndrome) to Xp22.2-p22.3. Ophthalmology. 1990;97(1):110–20. discussion 120-111.CrossRefPubMed
19.
Lewis RA. Mapping the gene for X-linked cataracts and microcornea with facial, dental, and skeletal features to Xp22: an appraisal of the Nance-Horan syndrome. Trans Am Ophthalmol Soc. 1989;87:658–728.PubMedPubMedCentral
20.
Stenson PD, Mort M, Ball EV, Shaw K, Phillips A, Cooper DN. The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. Hum Genet. 2014;133(1):1–9.CrossRefPubMed
21.
22.
23.
Sharma S, Ang SL, Shaw M, Mackey DA, Gecz J, McAvoy JW, Craig JE. Nance-Horan syndrome protein, NHS, associates with epithelial cell junctions. Hum Mol Genet. 2006;15(12):1972–83.CrossRefPubMed
24.
Khajavi M, Inoue K, Lupski JR. Nonsense-mediated mRNA decay modulates clinical outcome of genetic disease. Eur J Hum Genet. 2006;14(10):1074–81.CrossRefPubMed
Metadata
Title
A novel NHS mutation causes Nance-Horan Syndrome in a Chinese family
Authors
Qi Tian
Yunping Li
Rizwana Kousar
Hui Guo
Fenglan Peng
Yu Zheng
Xiaohua Yang
Zhigao Long
Runyi Tian
Kun Xia
Haiying Lin
Qian Pan
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2017
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-016-0360-9

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