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
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0225010
Souhrn
Purpose
To investigate the genetic basis of autosomal recessive congenital cataracts (arCC) in a large consanguineous Pakistani family.
Methods
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.
Results
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.
Conclusion
Here, we report a novel missense mutation in HSF4 associated with arCC in a familial case of Pakistani descent.
Klíčová slova:
Alleles – Transcription factors – Polymerase chain reaction – Substitution mutation – Eye lens – Cataracts – Missense mutation – Autosomal recessive traits
Zdroje
1. Robinson GC, Jan JE, Kinnis C. Congenital ocular blindness in children, 1945 to 1984 1502. Am J Dis Child (1987) 141: 1321–1324. doi: 10.1001/archpedi.1987.04460120087041 3687875
2. Hejtmancik JF, Smaoui N. Molecular genetics of cataract. Dev Ophthalmol (2003) 37: 67–82. doi: 10.1159/000072039 12876830
3. al-Ghoul KJ, Costello MJ. Fiber cell morphology and cytoplasmic texture in cataractous and normal human lens nuclei. Curr Eye Res (1996) 15: 533–542. doi: 10.3109/02713689609000764 8670754
4. Foster A, Johnson GJ Magnitude and causes of blindness in the developing world. Int Ophthalmol (1990) 14: 135–140. doi: 10.1007/bf00158310 2188914
5. Aldahmesh MA, Khan AO, Mohamed J, Alkuraya FS. Novel recessive BFSP2 and PITX3 mutations: insights into mutational mechanisms from consanguineous populations. Genetics in Medicine (2011) 13: 978. doi: 10.1097/GIM.0b013e31822623d5 21836522
6. Aldahmesh MA, Khan AO, Mohamed JY, Alghamdi MH, Alkuraya FS. Identification of a truncation mutation of acylglycerol kinase (AGK) gene in a novel autosomal recessive cataract locus. Hum Mutat (2012) 33: 960–962. doi: 10.1002/humu.22071 22415731
7. Ansar M, Chung Hl, Taylor RL, Nazir A, Imtiaz S, Sarwar MT et al. Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts. The American Journal of Human Genetics (2018) 103: 568–578. doi: 10.1016/j.ajhg.2018.09.004 30290152
8. Chen J, Ma Z, Jiao X, Fariss R, Kantorow WL, Kantorow M et al. Mutations in FYCO1 cause autosomal-recessive congenital cataracts. Am J Hum Genet (2011) 88: 827–838. doi: 10.1016/j.ajhg.2011.05.008 21636066
9. Chen J, Wang Q, Cabrera PE, Zhong Z, Sun W, Jiao X et al.Molecular Genetic Analysis of Pakistani Families With Autosomal Recessive Congenital Cataracts by Homozygosity Screening. Invest Ophthalmol Vis Sci (2017) 58: 2207–2217. doi: 10.1167/iovs.17-21469 28418495
10. Cohen D, Bar-Yosef U, Levy J, Gradstein L, Belfair N, Ofir R et al. Homozygous CRYBB1 deletion mutation underlies autosomal recessive congenital cataract. Invest Ophthalmol Vis Sci (2007) 48: 2208–2213. doi: 10.1167/iovs.06-1019 17460281
11. Greenlees R, Mihelec M, Yousoof S, Speidel D, Wu SK, Rinkwitz S et al.Mutations in SIPA1L3 cause eye defects through disruption of cell polarity and cytoskeleton organization. Hum Mol Genet (2015) 24: 5789–5804. doi: 10.1093/hmg/ddv298 26231217
12. Héon E, Paterson AD, Fraser M, Billingsley G, Priston M, Balmer A et al. A progressive autosomal recessive cataract locus maps to chromosome 9q13-q22. The American Journal of Human Genetics (2001) 68: 772–777. doi: 10.1086/318798 11179024
13. Jiaox X, Khan SY, Irum B, Khan AO, Wang Q, Kabir F et al. Missense Mutations in CRYAB Are Liable for Recessive Congenital Cataracts. PLoS One (2015) 10: e0137973. doi: 10.1371/journal.pone.0137973 26402864
14. Kaul H, Riazuddin SA, Shahid M, Kousar S, Butt NH, Zafar AU et al. Autosomal recessive congenital cataract linked to EPHA2 in a consanguineous Pakistani family. Mol Vis (2010) 16: 511–517. 20361013
15. Kaul H, Riazuddin SA, Yasmeen A, Mohsin S, Khan M, Nasir IA et al. A new locus for autosomal recessive congenital cataract identified in a Pakistani family. Mol Vis (2010) 16: 240–245. 20161816
16. Micheal S, Niewold ITsGl, Siddiqui SN, Zafar SN, Khan MI, Bergen A. A Delineation of Novel Autosomal Recessive Mutation in GJA3 and Autosomal Dominant Mutations in GJA8 in Pakistani Congenital Cataract Families. Genes (2018) 9: 112.
17. Ponnam SP, Ramesha K, Tejwani S, Ramamurthy B, Kannabiran C. Mutation of the gap junction protein alpha 8 (GJA8) gene causes autosomal recessive cataract. J Med Genet (2007) 44: e85. doi: 10.1136/jmg.2007.050138 17601931
18. Pras E, Frydman M, Levy-Nissenbaum E, Bakhan T, Raz J, Assia EI et al. A nonsense mutation (W9X) in CRYAA causes autosomal recessive cataract in an inbred Jewish Persian family. Invest Ophthalmol Vis Sci (2000) 41: 3511–3515. 11006246
19. Pras E, Levy-Nissenbaum E, Bakhan T, Lahat H, Assia E, Geffen-Carmi N et al. A missense mutation in the LIM2 gene is associated with autosomal recessive presenile cataract in an inbred Iraqi Jewish family. Am J Hum Genet (2002) 70: 1363–1367. doi: 10.1086/340318 11917274
20. Pras E, Raz J, Yahalom V, Frydman M, Garzozi HJ, Pras E et al. A nonsense mutation in the glucosaminyl (N-acetyl) transferase 2 gene (GCNT2): association with autosomal recessive congenital cataracts. Invest Ophthalmol Vis Sci (2004) 45: 1940–1945. doi: 10.1167/iovs.03-1117 15161861
21. Ramachandran RD, Perumalsamy V, Hejtmancik JF. Autosomal recessive juvenile onset cataract associated with mutation in BFSP1. Hum Genet (2007) 121: 475–482. doi: 10.1007/s00439-006-0319-6 17225135
22. Khan AO, Aldahmesh MA, Alkuraya FS. Phenotypes of recessive pediatric cataract in a cohort of children with identified homozygous gene mutations (An American Ophthalmological Society Thesis). Transactions of the American Ophthalmological Society. 2015;113.
23. Riazuddin SA, Yasmeen A, Yao W, Sergeev YV, Zhang Q, Zulfiqar F et al. Mutations in betaB3-crystallin associated with autosomal recessive cataract in two Pakistani families. Invest Ophthalmol Vis Sci (2005) 46: 2100–2106. doi: 10.1167/iovs.04-1481 15914629
24. Sabir N, Riazuddin SA, Kaul H, Iqbal F, Nasir IA, Zafar AU et al. Mapping of a novel locus associated with autosomal recessive congenital cataract to chromosome 8p. Mol Vis (2010) 16: 2911–2915. 21203409
25. Sabir N, Riazuddin SA, Butt T, Iqbal F, Nasir IA, Zafar AU et al. Mapping of a new locus associated with autosomal recessive congenital cataract to chromosome 3q. Molecular Vision (2010) 16: 2634. 21179239
26. Smaoui N, Beltaief O, BenHamed S, M’Rad R, Maazoul F, Ouertani A et al. A homozygous splice mutation in the HSF4 gene is associated with an autosomal recessive congenital cataract. Invest Ophthalmol Vis Sci (2004) 45: 2716–2721. doi: 10.1167/iovs.03-1370 15277496
27. Zhao L, Chen XJ, Zhu J, et al. Lanosterol reverses protein aggregation in cataracts. Nature. 2015;523:607–611. doi: 10.1038/nature14650 26200341
28. Nakai A, Tanabe M, Kawazoe Y, Inazawa J, Morimoto RI, Nagata K. HSF4, a new member of the human heat shock factor family which lacks properties of a transcriptional activator. Mol Cell Biol (1997) 17: 469–481. doi: 10.1128/mcb.17.1.469 8972228
29. Tanabe M, Sasai N, Nagata K, Liu XD, Liu PC, Thiele DJ et al. The mammalian HSF4 gene generates both an activator and a repressor of heat shock genes by alternative splicing. J Biol Chem (1999) 274: 27845–27856. doi: 10.1074/jbc.274.39.27845 10488131
30. Fujimoto M, Izu H, Seki K, Fukuda K, Nishida T, Yamada S et al. HSF4 is required for normal cell growth and differentiation during mouse lens development. EMBO J (2004) 23: 4297–4306. doi: 10.1038/sj.emboj.7600435 15483628
31. Lathrop GM, Lalouel JM. Easy calculations of lod scores and genetic risks on small computers. Am J Hum Genet (1984) 36: 460. 6585139
32. Schaffer AA, Gupta SK, Shriram K, Cottingham RW Jr. Avoiding recomputation in linkage analysis. Hum Hered (1994) 44: 225–237. doi: 10.1159/000154222 8056435
33. Merath K, Ronchetti A, Sidjanin DJ. Functional analysis of HSF4 mutations found in patients with autosomal recessive congenital cataracts. Invest Ophthalmol Vis Sci (2013) 54: 6646–6654. doi: 10.1167/iovs.13-12283 24045990
34. Khan SY, Hackett SF, Lee MC, Pourmand N, Talbot CC Jr., Riazuddin SA. Transcriptome Profiling of Developing Murine Lens Through RNA Sequencing. Invest Ophthalmol Vis Sci (2015) 56: 4919–4926. doi: 10.1167/iovs.14-16253 26225632
35. Anand D, Agrawal SA, Slavotinek A, Lachke SA. Mutation update of transcription factor genes FOXE3, HSF4, MAF, and PITX3 causing cataracts and other developmental ocular defects. Human mutation (2018) 39: 471–494. doi: 10.1002/humu.23395 29314435
36. Forshew T, Johnson CA, Khaliq S, Pasha S, Willis C, Abbasi R et al. Locus heterogeneity in autosomal recessive congenital cataracts: linkage to 9q and germline HSF4 mutations. Hum Genet (2005) 117: 452–459. doi: 10.1007/s00439-005-1309-9 15959809
37. Enoki Y, Mukoda Y, Furutani C, Sakurai H. DNA-binding and transcriptional activities of human HSF4 containing mutations that associate with congenital and age-related cataracts. Biochim Biophys Acta (2010) 1802: 749–753. doi: 10.1016/j.bbadis.2010.06.001 20670914
38. Cao Z, Zhu Y, Liu L, Wu S, Liu B, Zhuang J, Tong Y, Chen X, Xie Y, Nie K, Lu C, Ma X, Yang J (2018) Novel mutations in HSF4 cause congenital cataracts in Chinese families. BMC Med Genet 19: 150. doi: 10.1186/s12881-018-0636-3 30143024
Článok vyšiel v časopise
PLOS One
2019 Číslo 12
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Nejasný stín na plicích – kazuistika
- Masturbační chování žen v ČR − dotazníková studie
- Profylaxe infekční endokarditidy ve stomatologii
- Fixní kombinace paracetamol/kodein nabízí synergické analgetické účinky
Najčítanejšie v tomto čísle
- Methylsulfonylmethane increases osteogenesis and regulates the mineralization of the matrix by transglutaminase 2 in SHED cells
- Oregano powder reduces Streptococcus and increases SCFA concentration in a mixed bacterial culture assay
- The characteristic of patulous eustachian tube patients diagnosed by the JOS diagnostic criteria
- Parametric CAD modeling for open source scientific hardware: Comparing OpenSCAD and FreeCAD Python scripts