A 127 kb truncating deletion of PGRMC1 is a novel cause of X-linked isolated paediatric cataract.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
04
12
2020
accepted:
02
04
2021
revised:
10
03
2021
pubmed:
20
4
2021
medline:
17
3
2022
entrez:
19
4
2021
Statut:
ppublish
Résumé
Inherited paediatric cataract is a rare Mendelian disease that results in visual impairment or blindness due to a clouding of the eye's crystalline lens. Here we report an Australian family with isolated paediatric cataract, which we had previously mapped to Xq24. Linkage at Xq24-25 (LOD = 2.53) was confirmed, and the region refined with a denser marker map. In addition, two autosomal regions with suggestive evidence of linkage were observed. A segregating 127 kb deletion (chrX:g.118373226_118500408del) in the Xq24-25 linkage region was identified from whole-genome sequencing data. This deletion completely removed a commonly deleted long non-coding RNA gene LOC101928336 and truncated the protein coding progesterone receptor membrane component 1 (PGRMC1) gene following exon 1. A literature search revealed a report of two unrelated males with non-syndromic intellectual disability, as well as congenital cataract, who had contiguous gene deletions that accounted for their intellectual disability but also disrupted the PGRMC1 gene. A morpholino-induced pgrmc1 knockdown in a zebrafish model produced significant cataract formation, supporting a role for PGRMC1 in lens development and cataract formation. We hypothesise that the loss of PGRMC1 causes cataract through disrupted PGRMC1-CYP51A1 protein-protein interactions and altered cholesterol biosynthesis. The cause of paediatric cataract in this family is the truncating deletion of PGRMC1, which we report as a novel cataract gene.
Identifiants
pubmed: 33867527
doi: 10.1038/s41431-021-00889-8
pii: 10.1038/s41431-021-00889-8
pmc: PMC8385038
doi:
Substances chimiques
CYP51A1 protein, human
0
Membrane Proteins
0
PGRMC1 protein, human
0
Receptors, Progesterone
0
Sterol 14-Demethylase
EC 1.14.14.154
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1206-1215Informations de copyright
© 2021. The Author(s).
Références
Wu X, Long E, Lin H, Liu Y. Prevalence and epidemiological characteristics of congenital cataract: a systematic review and meta-analysis. Sci Rep. 2016;6:28564.
pubmed: 27334676
pmcid: 4917826
doi: 10.1038/srep28564
Wirth MG, Russell-Eggitt IM, Craig JE, Elder JE, Mackey DA. Aetiology of congenital and paediatric cataract in an Australian population. Br J Ophthalmol. 2002;86:782–6.
pubmed: 12084750
pmcid: 1771196
doi: 10.1136/bjo.86.7.782
Shiels A, Hejtmancik JF. Genetic origins of cataract. Arch Ophthalmol. 2007;125:165–73.
pubmed: 17296892
doi: 10.1001/archopht.125.2.165
Francois J. Genetics of cataract. Ophthalmologica. 1982;184:61–71.
pubmed: 7063172
doi: 10.1159/000309186
Merin S, Crawford JS. The etiology of congenital cataracts. A survey of 386 cases. Can J Ophthalmol. 1971;6:178–82.
pubmed: 4254831
Shiels A, Bennett TM, Hejtmancik JF. Cat-Map: putting cataract on the map. Mol Vis. 2010;16:2007–15.
pubmed: 21042563
pmcid: 2965572
Reis LM, Semina EV. Genetic landscape of isolated pediatric cataracts: extreme heterogeneity and variable inheritance patterns within genes. Hum Genet. 2019;138:847–63.
pubmed: 30187164
doi: 10.1007/s00439-018-1932-x
Coccia M, Brooks SP, Webb TR, Christodoulou K, Wozniak IO, Murday V, et al. X-linked cataract and Nance-Horan syndrome are allelic disorders. Hum Mol Genet. 2009;18:2643–55.
pubmed: 19414485
pmcid: 2701339
doi: 10.1093/hmg/ddp206
Francis PJ, Berry V, Hardcastle AJ, Maher ER, Moore AT, Bhattacharya SS. A locus for isolated cataract on human Xp. J Med Genet. 2002;39:105–9.
pubmed: 11836358
pmcid: 1735039
doi: 10.1136/jmg.39.2.105
Brooks S, Ebenezer N, Poopalasundaram S, Maher E, Francis P, Moore A, et al. Refinement of the X-linked cataract locus (CXN) and gene analysis for CXN and Nance-Horan syndrome (NHS). Ophthalmic Genet. 2004;25:121–31.
pubmed: 15370543
doi: 10.1080/13816810490514360
Burdon KP, McKay JD, Sale MM, Russell-Eggitt IM, Mackey DA, Wirth MG, et al. Mutations in a novel gene, NHS, cause the pleiotropic effects of Nance-Horan syndrome, including severe congenital cataract, dental anomalies, and mental retardation. Am J Hum Genet. 2003;73:1120–30.
pubmed: 14564667
pmcid: 1180491
doi: 10.1086/379381
Craig JE, Friend KL, Gecz J, Rattray KM, Troski M, Mackey DA, et al. A novel locus for X-linked congenital cataract on Xq24. Mol Vis. 2008;14:721–6.
pubmed: 18431456
pmcid: 2324122
Mitchell P, Smith W, Attebo K, Healey PR. Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study. Ophthalmology. 1996;103:1661–9.
pubmed: 8874440
doi: 10.1016/S0161-6420(96)30449-1
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559–75.
pubmed: 17701901
pmcid: 1950838
doi: 10.1086/519795
Burdon KP, Fogarty RD, Shen W, Abhary S, Kaidonis G, Appukuttan B, et al. Genome-wide association study for sight-threatening diabetic retinopathy reveals association with genetic variation near the GRB2 gene. Diabetologia. 2015;58:2288–97.
pubmed: 26188370
doi: 10.1007/s00125-015-3697-2
Baron RV, Kollar C, Mukhopadhyay N, Weeks DE. Mega2: validated data-reformatting for linkage and association analyses. Source Code Biol Med. 2014;9:26.
pubmed: 25687422
pmcid: 4269913
doi: 10.1186/s13029-014-0026-y
Baron RV, Kollar CP, Mukhopadhyay N, Almasy N, Schroeder M, Mulvihill WP, et al. Mega2 (Version 4.9.2) 2015. Available from: https://watson.hgen.pitt.edu/mega2.html .
Abecasis GR, Cherny SS, Cookson WO, Cardon LR. Merlin-rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet. 2002;30:97–101.
pubmed: 11731797
doi: 10.1038/ng786
Abecasis GR, Wigginton JE. Handling marker-marker linkage disequilibrium: pedigree analysis with clustered markers. Am J Hum Genet. 2005;77:754–67.
pubmed: 16252236
pmcid: 1271385
doi: 10.1086/497345
Drmanac R, Sparks AB, Callow MJ, Halpern AL, Burns NL, Kermani BG, et al. Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays. Science. 2010;327:78–81.
pubmed: 19892942
doi: 10.1126/science.1181498
Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38:e164.
pubmed: 20601685
pmcid: 2938201
doi: 10.1093/nar/gkq603
Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden TL. Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction. BMC Bioinforma. 2012;13:134.
doi: 10.1186/1471-2105-13-134
Westerfield M. The zebrafish book: a guide for the laboratory use of zebrafish (Danio rerio). Eugene: University of Oregon Press, 2000.
Scott EK, Mason L, Arrenberg AB, Ziv L, Gosse NJ, Xiao T, et al. Targeting neural circuitry in zebrafish using GAL4 enhancer trapping. Nat Methods. 2007;4:323–6.
pubmed: 17369834
doi: 10.1038/nmeth1033
Scott EK, Baier H. The cellular architecture of the larval zebrafish tectum, as revealed by gal4 enhancer trap lines. Front Neural Circuits. 2009;3:13.
pubmed: 19862330
pmcid: 2763897
doi: 10.3389/neuro.04.013.2009
Aizen J, Pang Y, Harris C, Converse A, Zhu Y, Aguirre MA, et al. Roles of progesterone receptor membrane component 1 and membrane progestin receptor alpha in regulation of zebrafish oocyte maturation. Gen Comp Endocrinol. 2018;263:51–61.
pubmed: 29649418
pmcid: 6480306
doi: 10.1016/j.ygcen.2018.04.009
Li X, Rhee DK, Malhotra R, Mayeur C, Hurst LA, Ager E, et al. Progesterone receptor membrane component-1 regulates hepcidin biosynthesis. J Clin Investig. 2016;126:389–401.
pubmed: 26657863
doi: 10.1172/JCI83831
Froger A, Clemens D, Kalman K, Nemeth-Cahalan KL, Schilling TF, Hall JE. Two distinct aquaporin 0s required for development and transparency of the zebrafish lens. Investig Ophthalmol Vis Sci. 2010;51:6582–92.
doi: 10.1167/iovs.10-5626
Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9:671–5.
pubmed: 22930834
pmcid: 5554542
doi: 10.1038/nmeth.2089
Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39:175–91.
Ng PC, Henikoff S. Predicting deleterious amino acid substitutions. Genome Res. 2001;11:863–74.
pubmed: 11337480
pmcid: 311071
doi: 10.1101/gr.176601
Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7:248–9.
pubmed: 20354512
pmcid: 2855889
doi: 10.1038/nmeth0410-248
Lizio M, Harshbarger J, Shimoji H, Severin J, Kasukawa T, Sahin S, et al. Gateways to the FANTOM5 promoter level mammalian expression atlas. Genome Biol. 2015;16:22.
pubmed: 25723102
pmcid: 4310165
doi: 10.1186/s13059-014-0560-6
MacDonald JR, Ziman R, Yuen RK, Feuk L, Scherer SW. The Database of Genomic Variants: a curated collection of structural variation in the human genome. Nucleic Acids Res. 2014;42:D986–92.
pubmed: 24174537
doi: 10.1093/nar/gkt958
Wong LP, Ong RT, Poh WT, Liu X, Chen P, Li R, et al. Deep whole-genome sequencing of 100 southeast Asian Malays. Am J Hum Genet. 2013;92:52–66.
pubmed: 23290073
pmcid: 3542459
doi: 10.1016/j.ajhg.2012.12.005
Abugessaisa I, Shimoji H, Sahin S, Kondo A, Harshbarger J, Lizio M, et al. FANTOM5 transcriptome catalog of cellular states based on Semantic MediaWiki. Database. 2016;2016,baw105. https://doi.org/10.1093/database/baw105 .
Collins RL, Brand H, Karczewski KJ, Zhao X, Alföldi J, Francioli LC, et al. A structural variation reference for medical and population genetics. Nature. 2020;581:444–51.
pubmed: 32461652
pmcid: 7334194
doi: 10.1038/s41586-020-2287-8
Vandewalle J, Bauters M, Van Esch H, Belet S, Verbeeck J, Fieremans N, et al. The mitochondrial solute carrier SLC25A5 at Xq24 is a novel candidate gene for non-syndromic intellectual disability. Hum Genet. 2013;132:1177–85.
pubmed: 23783460
doi: 10.1007/s00439-013-1322-3
Hughes AL, Powell DW, Bard M, Eckstein J, Barbuch R, Link AJ, et al. Dap1/PGRMC1 binds and regulates cytochrome P450 enzymes. Cell Metab. 2007;5:143–9.
pubmed: 17276356
doi: 10.1016/j.cmet.2006.12.009
Asperger H, Stamm N, Gierke B, Pawlak M, Hofmann U, Zanger UM, et al. Progesterone receptor membrane component 1 regulates lipid homeostasis and drives oncogenic signaling resulting in breast cancer progression. Breast Cancer Res. 2020;22:75.
pubmed: 32660617
pmcid: 7359014
doi: 10.1186/s13058-020-01312-8
Nebert DW, Russell DW. Clinical importance of the cytochromes P450. Lancet. 2002;360:1155–62.
pubmed: 12387968
doi: 10.1016/S0140-6736(02)11203-7
Aldahmesh MA, Khan AO, Mohamed JY, Hijazi H, Al-Owain M, Alswaid A, et al. Genomic analysis of pediatric cataract in Saudi Arabia reveals novel candidate disease genes. Genet Med. 2012;14:955–62.
pubmed: 22935719
doi: 10.1038/gim.2012.86
Patel N, Anand D, Monies D, Maddirevula S, Khan AO, Algoufi T, et al. Novel phenotypes and loci identified through clinical genomics approaches to pediatric cataract. Hum Genet. 2017;136:205–25.
pubmed: 27878435
doi: 10.1007/s00439-016-1747-6
Gillespie RL, O’Sullivan J, Ashworth J, Bhaskar S, Williams S, Biswas S, et al. Personalized diagnosis and management of congenital cataract by next-generation sequencing. Ophthalmology. 2014;121:2124–37.e1-2.
pubmed: 25148791
doi: 10.1016/j.ophtha.2014.06.006
Mori M, Li G, Abe I, Nakayama J, Guo Z, Sawashita J, et al. Lanosterol synthase mutations cause cholesterol deficiency-associated cataracts in the Shumiya cataract rat. J Clin Investig. 2006;116:395–404.
pubmed: 16440058
pmcid: 1350995
doi: 10.1172/JCI20797
Zhao L, Chen XJ, Zhu J, Xi YB, Yang X, Hu LD, et al. Lanosterol reverses protein aggregation in cataracts. Nature. 2015;523:607–11.
pubmed: 26200341
doi: 10.1038/nature14650
Widomska J, Subczynski WK, Mainali L, Raguz M. Cholesterol bilayer domains in the eye lens health: a review. Cell Biochem Biophysics. 2017;75:387–98.
doi: 10.1007/s12013-017-0812-7