A mutation within exon 14 of the TGFBI (BIGH3) gene on chromosome 5q31 causes an asymmetric, late-onset form of lattice corneal dystrophy☆
Section snippets
Clinical data
Three unrelated families were included in the study. Informed consent was obtained from those participating in this study. Ethical approval was obtained from Manchester Health Commission, Research Ethics Committee (Central), reference CM/96/043. Families 1, 2, and 3 were of 6, 4, and 3 generations, respectively. Most family members were examined by GB or AR by slit lamp for correct clinical ascertainment, and GB counseled the families. DNA was obtained from 11 affected and 8 unaffected
Clinical details
Of the affected individuals in 3 families older than the age of 30 years, 14 were available for examination as part of this study. The age at onset of symptoms was between 28 and 48, with a mean of 37 years (Table 1). At onset, symptoms related to either visual loss or recurrent erosion, both of which were usually unilateral at that stage. One patient reported photophobia. Ultimately, keratoplasty was performed in all but one individual. As patients were followed, progress was most commonly
Discussion
The TGFBI gene is now implicated in the pathogenesis of several anterior stromal dystrophies: Avellino, granular, Reis-Buckler, and two forms of isolated LCD, types I and IIIA.4 Type-IIIA LCD was recently shown to be the fifth clinically distinct corneal dystrophy due to a mutation within the TGFBI gene.10 Here we present evidence that two mutations, N622H and H626R, both in exon 14, cause a form of late-onset LCD. The H626R mutation identified cosegregates with the disease phenotype in
Acknowledgements
The authors thank the members of the families studied for their invaluable contribution to this project and Georgina Hall for her assistance in pedigree data and sample collection. The authors also thank the staff in the Dixon and Black laboratories for their invaluable technical advice.
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2016, Progress in Retinal and Eye ResearchCitation Excerpt :The p.His626Arg mutation is associated with asymmetric thick lattice lines in the anterior and mid-stroma, with a relatively late onset during the 3rd to 4th decades of life (Dighiero et al., 2001; Munier et al., 2002; Schmitt-Bernard et al., 2000b; Stewart et al., 1999a). Notes for variant LCD Numerous types of variant LCD have been reported to be associated with p.Arg496Trp (Kawasaki et al., 2011), p.Pro501Thr (Mashima et al., 2000; Yamamoto et al., 1998; Yu et al., 2006), p.Thr538Arg (Munier et al., 2002; Pampukha et al., 2008), p.Phe540del (Munier et al., 2002), p.Phe540Ser (Stix et al., 2005), p.Pro542Arg (Cho et al., 2012), p.Asn544Ser (Mashima et al., 2000; Yamada et al., 2009), p.Ala546Asp (Correa-Gomez et al., 2007; Eifrig et al., 2004), p.Ala546Thr (Dighiero et al., 2000b, 2001), p.Phe547Ser (Takacs et al., 2007), p.Leu565Pro (Oldak et al., 2014), p.His572del (Aldave et al., 2006), p.Gly594Val (Chakravarthi et al., 2005), p.Val613Gly (Niel-Butschi et al., 2011), p.Val613_Pro616del (Yang et al., 2010), p.Ala620Asp (Lakshminarayanan et al., 2011), p.Ala620Asp (Lakshminarayanan et al., 2011), p.Ala620Pro (Jung et al., 2014), p.Asn622His (Stewart et al., 1999a), p.Asn622Lys (Munier et al., 2002), p.Gly623Asp (Munier et al., 2002), p.His626Arg (Dighiero et al., 2001; Munier et al., 2002; Schmitt-Bernard et al., 2000b; Stewart et al., 1999a), p.His626Pro (Munier et al., 2002), p.Val624_Val625del (Chakravarthi et al., 2005), p.Val627Ter (Munier et al., 2002), p.Asn629_Pro630ins3 (Schmitt-Bernard et al., 2000b), and p.Val631Asp (Munier et al., 2002). GCD1 is an autosomal dominant disease, which was first described by Groenouw (Groenouw, 1890).
Clinical and genetic aspects of the TGFBI-associated corneal dystrophies
2014, Ocular SurfaceCitation Excerpt :The phenotype associated with p.Asp123His is late in onset, less severe, and of low penetrance compared to the classical GCD1.42 However, the p.Arg124Ser mutation results in a severe phenotype with extensive granular deposits in the posterior cornea.43 Two of the three mutations in the 4th FAS1 associated with GCD1 are single amino acid substitutions, namely p.Ser516Arg mutation, which is associated with a severe phenotype, and p.Leu559Val mutation with a less severe clinical phenotype.44
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Supported by the Wellcome trust (Reference 51390/Z) (GB).
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Drs. Stewart and Black contributed equally to this work.