PURPOSE: To identify the genetic basis of Schnyder crystalline corneal dystrophy (SCCD) through screening positional candidate genes and UBIAD1, in which mutations have been associated with SCCD, in affected families. METHODS: The coding region of each of the 16 positional candidate genes for which mutation screening has not been previously reported was screened with polymerase chain reaction (PCR) amplification and automated sequencing in four affected individuals from two families with SCCD. In addition, the coding region of UBIAD1, located just outside of the originally described SCCD candidate interval on chromosome 1p36, was directly sequenced in affected and unaffected individuals from three families with SCCD. RESULTS: Eighteen novel and 15 previously reported sequence variants were identified in 10 of the 16 positional candidate genes. Only two of the sequence variants segregated with the affected phenotype in either of the families screened. Both were novel single nucleotide polymorphisms (SNPs) predicted to result in synonymous amino acid substitutions in different predicted genes. However, one of these SNPs was also identified in control individuals, and the other SNP was not predicted to alter splicing. Screening of UBIAD1 revealed a different missense mutation in each of the three unrelated probands that was screened: p.Asn102Ser, p.Arg119Gly, and p.Leu121Val. Screening of the affected and unaffected relatives of the probands in whom the p.Asn102Ser and p.Leu121Val mutations were identified demonstrated that each mutation segregated with the affected phenotype. None of the three missense mutations was identified in 110 control individuals. CONCLUSIONS: No presumed pathogenic coding region mutations were identified in the genes mapped to the candidate region for SCCD. However, missense mutations in UBIAD1, located just outside of the originally described SCCD fine mapped region, were identified in each of the three families with SCCD, confirming that mutations in UBIAD1 are associated with SCCD.
PURPOSE: To identify the genetic basis of Schnyder crystalline corneal dystrophy (SCCD) through screening positional candidate genes and UBIAD1, in which mutations have been associated with SCCD, in affected families. METHODS: The coding region of each of the 16 positional candidate genes for which mutation screening has not been previously reported was screened with polymerase chain reaction (PCR) amplification and automated sequencing in four affected individuals from two families with SCCD. In addition, the coding region of UBIAD1, located just outside of the originally described SCCD candidate interval on chromosome 1p36, was directly sequenced in affected and unaffected individuals from three families with SCCD. RESULTS: Eighteen novel and 15 previously reported sequence variants were identified in 10 of the 16 positional candidate genes. Only two of the sequence variants segregated with the affected phenotype in either of the families screened. Both were novel single nucleotide polymorphisms (SNPs) predicted to result in synonymous amino acid substitutions in different predicted genes. However, one of these SNPs was also identified in control individuals, and the other SNP was not predicted to alter splicing. Screening of UBIAD1 revealed a different missense mutation in each of the three unrelated probands that was screened: p.Asn102Ser, p.Arg119Gly, and p.Leu121Val. Screening of the affected and unaffected relatives of the probands in whom the p.Asn102Ser and p.Leu121Val mutations were identified demonstrated that each mutation segregated with the affected phenotype. None of the three missense mutations was identified in 110 control individuals. CONCLUSIONS: No presumed pathogenic coding region mutations were identified in the genes mapped to the candidate region for SCCD. However, missense mutations in UBIAD1, located just outside of the originally described SCCD fine mapped region, were identified in each of the three families with SCCD, confirming that mutations in UBIAD1 are associated with SCCD.
Authors: Kathryn P Burdon; Douglas J Coster; Jac C Charlesworth; Richard A Mills; Kate J Laurie; Cecilia Giunta; Alex W Hewitt; Paul Latimer; Jamie E Craig Journal: Hum Genet Date: 2008-09-05 Impact factor: 4.132
Authors: Michael L Nickerson; Allen D Bosley; Jayne S Weiss; Brittany N Kostiha; Yoshihisa Hirota; Wolfgang Brandt; Dominic Esposito; Shigeru Kinoshita; Ludger Wessjohann; Scott G Morham; Thorkell Andresson; Howard S Kruth; Toshio Okano; Michael Dean Journal: Hum Mutat Date: 2012-11-27 Impact factor: 4.878
Authors: Michael L Nickerson; Brittany N Kostiha; Wolfgang Brandt; William Fredericks; Ke-Ping Xu; Fu-Shin Yu; Bert Gold; James Chodosh; Marc Goldberg; Da Wen Lu; Masakazu Yamada; Timo M Tervo; Richard Grutzmacher; Chris Croasdale; Maria Hoeltzenbein; John Sutphin; S Bruce Malkowicz; Ludger Wessjohann; Howard S Kruth; Michael Dean; Jayne S Weiss Journal: PLoS One Date: 2010-05-21 Impact factor: 3.240
Authors: Anthony J Aldave; Vivek S Yellore; Rosalind C Vo; Khairidzan M Kamal; Sylvia A Rayner; Christopher L Plaisier; Michael C Chen; Mausam R Damani; Michele N Pham; Michael B Gorin; Eric Sobel; Jeanette Papp Journal: Cornea Date: 2009-08 Impact factor: 2.651
Authors: Jayne S Weiss; H U Møller; Walter Lisch; Shigeru Kinoshita; Anthony J Aldave; Michael W Belin; Tero Kivelä; Massimo Busin; Francis L Munier; Berthold Seitz; John Sutphin; Cecilie Bredrup; Mark J Mannis; Christopher J Rapuano; Gabriel Van Rij; Eung Kweon Kim; Gordon K Klintworth Journal: Cornea Date: 2008-12 Impact factor: 2.651
Authors: Vera Mugoni; Ruben Postel; Valeria Catanzaro; Elisa De Luca; Emilia Turco; Giuseppe Digilio; Lorenzo Silengo; Michael P Murphy; Claudio Medana; Didier Y R Stainier; Jeroen Bakkers; Massimo M Santoro Journal: Cell Date: 2013-01-31 Impact factor: 41.582