Novel missense mutation in the bZIP transcription factor, MAF, associated with congenital cataract, developmental delay, seizures and hearing loss (Aymé-Gripp …
S Javadiyan, JE Craig, S Sharma, KM Lower… - BMC medical …, 2017 - Springer
BMC medical genetics, 2017•Springer
Background Cataract is a major cause of severe visual impairment in childhood. The
purpose of this study was to determine the genetic cause of syndromic congenital cataract in
an Australian mother and son. Method Fifty-one genes associated with congenital cataract
were sequenced in the proband using a custom Ampliseq library on the Ion Torrent Personal
Genome Machine (PGM). Reads were aligned against the human genome (hg19) and
variants were annotated. Variants were prioritised for validation by Sanger sequencing if …
purpose of this study was to determine the genetic cause of syndromic congenital cataract in
an Australian mother and son. Method Fifty-one genes associated with congenital cataract
were sequenced in the proband using a custom Ampliseq library on the Ion Torrent Personal
Genome Machine (PGM). Reads were aligned against the human genome (hg19) and
variants were annotated. Variants were prioritised for validation by Sanger sequencing if …
Background
Cataract is a major cause of severe visual impairment in childhood. The purpose of this study was to determine the genetic cause of syndromic congenital cataract in an Australian mother and son.
Method
Fifty-one genes associated with congenital cataract were sequenced in the proband using a custom Ampliseq library on the Ion Torrent Personal Genome Machine (PGM). Reads were aligned against the human genome (hg19) and variants were annotated. Variants were prioritised for validation by Sanger sequencing if they were novel, rare or previously reported to be associated with paediatric cataract and were predicted to be protein changing. Variants were assessed for segregation with the phenotype in the affected mother.
Result
A novel likely pathogenic variant was identified in the transactivation domain of the MAF gene (c.176C > G, p.(Pro59Arg)) in the proband and his affected mother., but was absent in 326 unrelated controls and absent from public variant databases.
Conclusion
The MAF variant is the likely cause of the congenital cataract, Asperger syndrome, seizures, hearing loss and facial characteristics in the proband, providinga diagnosis of Aymé-Gripp syndrome for the family.
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