Autosomal recessive congenital cataracts linked to HSF4 in a consanguineous Pakistani family

Autoři: Xiaodong Jiao aff001;  Shahid Y. Khan aff002;  Haiba Kaul aff003;  Tariq Butt aff003;  Muhammad Asif Naeem aff003;  Sheikh Riazuddin aff003;  J. Fielding Hejtmancik aff001;  S. Amer Riazuddin aff002
Působiště autorů: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America aff001;  The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America aff002;  National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan aff003;  Allama Iqbal Medical College, University of Health Sciences, Lahore, Pakistan aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article



To investigate the genetic basis of autosomal recessive congenital cataracts (arCC) in a large consanguineous Pakistani family.


All participating members of family, PKCC074 underwent an ophthalmic examination. Slit-lamp photographs were ascertained for affected individuals that have not been operated for the removal of the cataractous lens. A small aliquot of the blood sample was collected from all participating individuals and genomic DNAs were extracted. A genome-wide scan was performed with polymorphic short tandem repeat (STR) markers and the logarithm of odds (LOD) scores were calculated. All coding exons and exon-intron boundaries of HSF4 were sequenced and expression of Hsf4 in mouse ocular lens was investigated. The C-terminal FLAG-tagged wild-type and mutant HSF4b constructs were prepared to examine the nuclear localization pattern of the mutant protein.


The ophthalmological examinations suggested that nuclear cataracts are present in affected individuals. Genome-wide linkage analyses localized the critical interval to a 10.95 cM (14.17 Mb) interval on chromosome 16q with a maximum two-point LOD score of 4.51 at θ = 0. Sanger sequencing identified a novel missense mutation: c.433G>C (p.Ala145Pro) that segregated with the disease phenotype in the family and was not present in ethnically matched controls. Real-time PCR analysis identified the expression of HSF4 in mouse lens as early as embryonic day 15 with a steady level of expression thereafter. The immunofluorescence tracking confirmed that both wild-type and mutant HSF4 (p.Ala145Pro) proteins localized to the nucleus.


Here, we report a novel missense mutation in HSF4 associated with arCC in a familial case of Pakistani descent.

Klíčová slova:

Alleles – Cataracts – Eye lens – Missense mutation – Polymerase chain reaction – Substitution mutation – Transcription factors – Autosomal recessive traits


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