title: Novel SIL1 mutations in consanguineous Pakistani families mapping to chromosomes 5q31.
abstract: OBJECTIVE
  To investigate the genetic basis of Marinesco-Sjogren syndrome (MSS) in consanguineous Pakistani families.
  
  
  METHODS
  Two consanguineous Pakistani families with congenital cataract and muscular dystrophy were enrolled for this study. Detailed ophthalmic and systemic examination including slit lamp microscopy, electromyogram and computed tomography scans were performed to characterize the syndrome. Blood samples were collected from affected and unaffected individuals and a genome wide scan consisting of 382 polymorphic microsatellite markers was performed. Coding exons, exon-intron boundaries, 5' UTR, and 3' UTR of the candidate gene SIL1 residing in the linkage interval was sequenced bi-directionally.
  
  
  RESULTS
  Clinical examination of the affected members of families 60067 and 60078 revealed features of MSS. The linked interval at chromosome 5q31 harbors SIL1. Sequencing of SIL1 in family 60067 revealed a homozygous substitution; c1240C>T, leading to a premature substitution; p.Q414X. Similarly, sequencing of SIL1 in family 60078 identified a homozygous change; c.274C>T, leading to a non conservative substitution; p.R92W.
  
  
  CONCLUSIONS
  In conclusion, our data report two novel missense mutations in two consanguineous Pakistani families affected with MSS.
authors.affiliation: National Centre of Excellence in Molecular Biology, 87 West Canal Bank Road, Lahore 53700, Pakistan. amerriazuddin@ncemb.org
authors.forename: S Amer
authors.initials: SA
authors.lastname: Riazuddin
authors.forename: Laleh
authors.initials: L
authors.lastname: Amiri-Kordestani
authors.forename: Haiba
authors.initials: H
authors.lastname: Kaul
authors.forename: Tariq
authors.initials: T
authors.lastname: Butt
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jiao
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
authors.forename: J Fielding
authors.initials: JF
authors.lastname: Hejtmancik
mesh_terms: D000293:Adolescent; D001921:Brain / Q000473:pathology; D002648:Child; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010154:Pakistan; D010375:Pedigree; D013132:Spinocerebellar Degenerations / Q000235:genetics*; D014057:Tomography, X-Ray Computed
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C418483:SIL1 protein, human