TY - JOUR
T1 - Identification of a Novel ZNF469 Mutation in a Pakistani Family With Brittle Cornea Syndrome
AU - Micheal, Shazia
AU - Siddiqui, Sorath Noorani
AU - Zafar, Saemah Nuzhat
AU - Gabriëla Niewold, Ilse Therésia
AU - Khan, Muhammad Imran
AU - Bergen, Arthur A. B.
PY - 2019/6/1
Y1 - 2019/6/1
N2 - PURPOSE: Brittle cornea syndrome (BCS) is a rare recessive disorder affecting connective tissues, most prominently in the eye. Pathogenic mutations causing BCS have been identified in PRDM5 and ZNF469 genes. This study investigates the genetic cause of BCS in a large, consanguineous Pakistani family with 4 affected and 3 unaffected individuals. METHODS: The coding region and exon-intron splice junctions of PRDM5 and ZNF469 genes were amplified by polymerase chain reaction, and bidirectional Sanger sequencing was performed to find the pathogenic change responsible for causing the disease in the family. RESULTS: A novel homozygous duplication c.9831dupC (p.Arg3278GlnfsX197) in the ZNF469 gene was identified, which was found to be co-segregating with the disease in the family. CONCLUSIONS: This is the first report of a ZNF469 homozygous mutation causing a BCS phenotype in a consanguineous Pakistani family. Our data extend the mutation spectrum of ZNF469 variants implicated in BCS.
AB - PURPOSE: Brittle cornea syndrome (BCS) is a rare recessive disorder affecting connective tissues, most prominently in the eye. Pathogenic mutations causing BCS have been identified in PRDM5 and ZNF469 genes. This study investigates the genetic cause of BCS in a large, consanguineous Pakistani family with 4 affected and 3 unaffected individuals. METHODS: The coding region and exon-intron splice junctions of PRDM5 and ZNF469 genes were amplified by polymerase chain reaction, and bidirectional Sanger sequencing was performed to find the pathogenic change responsible for causing the disease in the family. RESULTS: A novel homozygous duplication c.9831dupC (p.Arg3278GlnfsX197) in the ZNF469 gene was identified, which was found to be co-segregating with the disease in the family. CONCLUSIONS: This is the first report of a ZNF469 homozygous mutation causing a BCS phenotype in a consanguineous Pakistani family. Our data extend the mutation spectrum of ZNF469 variants implicated in BCS.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85066061601&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30865045
U2 - https://doi.org/10.1097/ICO.0000000000001828
DO - https://doi.org/10.1097/ICO.0000000000001828
M3 - Article
C2 - 30865045
SN - 0277-3740
VL - 38
SP - 718
EP - 722
JO - Cornea
JF - Cornea
IS - 6
ER -