James A. Poulter, Manir Ali, David F

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Mutations in TSPAN12 Cause Autosomal-Dominant Familial Exudative Vitreoretinopathy James A. Poulter, Manir Ali, David F. Gilmour, Aine Rice, Hiroyuki Kondo, Kenshi Hayashi, David A. Mackey, Lisa S. Kearns, Jonathan B. Ruddle, Jamie E. Craig, Eric A. Pierce, Louise M. Downey, Moin D. Mohamed, Alexander F. Markham, Chris F. Inglehearn, Carmel Toomes The American Journal of Human Genetics Volume 86, Issue 2, Pages 248-253 (February 2010) DOI: 10.1016/j.ajhg.2010.01.012 Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 1 Clinical Appearance of FEVR Fundus photograph of the right eye of the proband from family 1 (individual III:2 in Figure S1), showing the retinal vessels drawn up in a retinal fold that is obscuring the macula. The American Journal of Human Genetics 2010 86, 248-253DOI: (10.1016/j.ajhg.2010.01.012) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 2 FEVR Is Caused by Mutations in TSPAN12 (A) Sequence traces of the seven mutations identified and the corresponding wild-type alleles. (B) Schematic diagram of TSPAN12, showing the locations of the mutations. (C) Schematic diagram of the TSPAN12 protein, showing the location of the mutations within the protein domains. The locations of the transmembrane domains were obtained from Kovalenko et al., 2005.32 The intramolecular disulfide bonds crucial for the correct folding of large extracellular loop are indicated by red dots. Because we were unable to assess the actual consequences of the two splicing mutations, only predicted protein outcomes are shown. The American Journal of Human Genetics 2010 86, 248-253DOI: (10.1016/j.ajhg.2010.01.012) Copyright © 2010 The American Society of Human Genetics Terms and Conditions

Figure 3 Protein Sequence Alignment of Human TSPAN12 with Its Orthologs Alignments were calculated with ClustalW.33 Accession numbers: Human, O95859; Orangutan, Q5R8B5; Mouse, AAH68240; Rat, Q569A2; Cattle, Q29RH7; Horse, XP_001502093; Dog, XP_855095; Opossum, XP_001364876; Chicken, XP_416007; Zebrafinch, XP_002192381; Platypus, XP_001516347; Zebrafish, NP_957446; Seasquirt Tspan,12 XP_002123238. Only 30 amino acid residues surrounding each mutation are shown. Conserved amino acid residues are highlighted. The positions of the missense mutations p.L101H and p.M210R are indicated. The American Journal of Human Genetics 2010 86, 248-253DOI: (10.1016/j.ajhg.2010.01.012) Copyright © 2010 The American Society of Human Genetics Terms and Conditions