Compound heterozygous mutations in the noncoding RNU4ATAC cause Roifman Syndrome by disrupting minor intron splicing

Nature Communications

Volumn 6, Issue , 2015, Pages

  Merico, Daniele ^a   Roifman, Maian ^b,c,d   Braunschweig, Ulrich ^e   Yuen, Ryan K C ^a   Alexandrova, Roumiana ^a   Bates, Andrea ^b   Reid, Brenda ^b   Nalpathamkalam, Thomas ^a   Wang, Zhuozhi ^a   Thiruvahindrapuram, Bhooma ^a   Gray, Paul ^f   Kakakios, Alyson ^g   Peake, Jane ^h,i   Hogarth, Stephanie ^h,i   Manson, David ^b   Buncic, Raymond ^b   Pereira, Sergio L ^a   Herbrick, Jo Anne ^a   Blencowe, Benjamin J ^e   Roifman, Chaim M ^b,d   Scherer, Stephen W ^a,d,e,j   more..

^a HOSPITAL FOR SICK CHILDREN   (Canada)

^b HOSPITAL FOR SICK CHILDREN   (Canada)

^c MOUNT SINAI HOSPITAL   (Canada)

^d UNIVERSITY OF TORONTO   (Canada)

^e UNIVERSITY OF TORONTO   (Canada)

^f SYDNEY CHILDREN'S HOSPITAL   (Australia)

^g CHILDREN S HOSPITAL AT WESTMEAD   (Australia)

^h LADY CILENTO CHILDREN S HOSPITAL   (Australia)

ⁱ UNIVERSITY OF QUEENSLAND   (Australia)

^j KING ABDULAZIZ UNIVERSITY   (Saudi Arabia)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ALLELE; ANTIBODY; COGNITION; DATA SET; DISEASE PREVALENCE; ENDOCRINE DISRUPTOR; GENE; GENOME; MUTATION; PHENOTYPE;

RNU4ATAC RNA, HUMAN; SMALL NUCLEAR RNA; UNTRANSLATED REGION;

ALLELE; CARDIOMYOPATHY; CHEMISTRY; CHONDRODYSPLASIA; CONFORMATION; DWARFISM; FEMALE; GENETICS; HUMAN; IMMUNE DEFICIENCY; INTRAUTERINE GROWTH RETARDATION; INTRON; MALE; MICROCEPHALY; MOLECULAR GENETICS; NUCLEOTIDE SEQUENCE; PEDIGREE; POINT MUTATION; PRESCHOOL CHILD; RETINA DISEASE; RNA SPLICING; UNTRANSLATED REGION; X LINKED MENTAL RETARDATION;

ALLELES; BASE SEQUENCE; CARDIOMYOPATHIES; CHILD, PRESCHOOL; DWARFISM; FEMALE; FETAL GROWTH RETARDATION; HUMANS; IMMUNOLOGIC DEFICIENCY SYNDROMES; INTRONS; MALE; MENTAL RETARDATION, X-LINKED; MICROCEPHALY; MOLECULAR SEQUENCE DATA; NUCLEIC ACID CONFORMATION; OSTEOCHONDRODYSPLASIAS; PEDIGREE; POINT MUTATION; RETINAL DISEASES; RNA SPLICING; RNA, SMALL NUCLEAR; UNTRANSLATED REGIONS;

EID: 84946210606     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms9718     Document Type: Article

References (61)

1. Roifman, C. M. Immunological aspects of a novel immunodeficiency syndrome that includes antibody deficiency with normal immunoglobulins, spondyloepiphyseal dysplasia, growth and developmental delay, and retinal dystrophy. Can. J. Allergy Clin. Immunol. 2, 94-98 (1997).
2. Roifman, C. M. Antibody deficiency, growth retardation, spondyloepiphyseal dysplasia and retinal dystrophy: a novel syndrome. Clin. Genet. 55, 103-109 (1999).
3. Robertson, S. P., Rodda, C. & Bankier, A. Hypogonadotrophic hypogonadism in Roifman syndrome. Clin. Genet. 57, 435-438 (2000).
4. Mandel, K., Grunebaum, E. & Benson, L. Noncompaction of the myocardium associated with Roifman syndrome. Cardiol. Young 11, 240-243 (2001).
5. de Vries, P. J., McCartney, D. L., McCartney, E., Woolf, D. & Wozencroft, D. The cognitive and behavioural phenotype of Roifman syndrome. J. Intellect. Disabil. Res. 50, 690-696 (2006).
6. Fairchild, H. R., et al. Partial agenesis of the corpus callosum, hippocampal atrophy, and stable intellectual disability associated with Roifman syndrome. Am. J. Med. Genet. 155A, 2560-2565 (2011).
7. Gray, P. E., Sillence, D. & Kakakios, A. Is Roifman syndrome an X-linked ciliopathy with humoral immunodeficiency? Evidence from 2 new cases. Int. J. Immunogenet. 38, 501-505 (2011).
8. Tarn, W. Y. & Steitz, J. A. Highly diverged U4 and U6 small nuclear RNAs required for splicing rare AT-AC introns. Science 273, 1824-1832 (1996).
9. Turunen, J. J., Niemelä, E. H., Verma, B. & Frilander, M. J. The significant other: splicing by the minor spliceosome. Wiley Interdiscip. Rev. RNA 4, 61-76 (2013).
10. Edery, P., et al. Association of TALS developmental disorder with defect in minor splicing component U4atac snRNA. Science 332, 240-243 (2011).
11. He, H., et al. Mutations in U4atac snRNA, a component of the minor spliceosome, in the developmental disorder MOPD I. Science 332, 238-240 (2011).
12. Argente, J., et al. Defective minor spliceosome mRNA processing results in isolated familial growth hormone deficiency. EMBO Mol. Med. 6, 299-306 (2014).
13. Taybi, H. & Linder, D. Congenital familial dwarfism with cephaloskeletal dysplasia. Radiology 89, 275-281 (1967).
14. Sigaudy, S., et al. Microcephalic osteodysplastic primordial dwarfism Taybi-Linder type: report of four cases and review of the literature. Am. J. Med. Genet. 80, 16-24 (1998).
15. Abdel-Salam, G. M., et al. A homozygous mutation in RNU4ATAC as a cause of microcephalic osteodysplastic primordial dwarfism type I (MOPD I) with associated pigmentary disorder. Am. J. Med. Genet. 155A, 2885-2896 (2011).
16. Nagy, R., et al. Microcephalic osteodysplastic primordial dwarfism type I with biallelic mutations in the RNU4ATAC gene. Clin. Genet. 82, 140-146 (2012).
17. Abdel-Salam, G. M., et al. Expanding the phenotypic and mutational spectrum in microcephalic osteodysplastic primordial dwarfism type I. Am. J. Med. Genet. 158A, 1455-1461 (2012).
18. Kilic, E., et al. A novel mutation in RNU4ATAC in a patient with microcephalic osteodysplastic primordial dwarfism type I. Am. J. Med. Genet. 167A, 919-921 (2015).
19. Will, C. L., Schneider, C., Reed, R. & Lührmann, R. Identification of both shared and distinct proteins in the major and minor spliceosomes. Science 284, 2003-2005 (1999).
20. Shukla, G. C. & Padgett, R. A. Conservation of functional features of U6atac and U12 snRNAs between vertebrates and higher plants. RNA 5, 525-538 (1999).
21. Shukla, G. C., Cole, A. J., Dietrich, R. C. & Padgett, R. A. Domains of human U4atac snRNA required for U12-dependent splicing in vivo. Nucleic Acids Res. 30, 4650-4657 (2002).
22. Jafarifar, F., Dietrich, R. C., Hiznay, J. M. & Padgett, R. A. Biochemical defects in minor spliceosome function in the developmental disorder MOPD I. RNA 20, 1078-1089 (2014).
23. Braunschweig, U., et al. Widespread intron retention in mammals functionally tunes transcriptomes. Genome Res. 24, 1774-1786 (2014).
24. Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139-140 (2010).
25. Trapnell, C., et al. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat. Biotechnol. 28, 511-515 (2010).
26. Anders, S. & Huber, W. Differential expression analysis for sequence count data. Genome Biol. 11, R106 (2010).
27. Mezlini, A. M., et al. iReckon: simultaneous isoform discovery and abundance estimation from RNA-seq data. Genome Res. 23, 519-529 (2013).
28. Chantret, I., et al. Congenital disorders of glycosylation type Ig is defined by a deficiency in dolichyl-P-mannose:Man7GlcNAc2-PP-dolichyl mannosyltransferase. J. Biol. Chem. 277, 25815-25822 (2002).
29. Zhu, C., Bogue, M. A., Lim, D. S., Hasty, P. & Roth, D. B. Ku86-deficient mice exhibit severe combined immunodeficiency and defective processing of V(D)J recombination intermediates. Cell 86, 379-389 (1996).
30. Nussenzweig, A., et al. Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature 382, 551-555 (1996).
31. Roberts, S. A., et al. Ku is a 50-dRP/AP lyase that excises nucleotide damage near broken ends. Nature 464, 1214-1217 (2010).
32. Deardorff, M. A., et al. Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of Cornelia de Lange syndrome with predominant mental retardation. Am. J. Hum. Genet. 80, 485-494 (2007).
33. Morrow, E. M., et al. Identifying autism loci and genes by tracing recent shared ancestry. Science 321, 218-223 (2008).
34. Lubas, M., et al. Interaction profiling identifies the human nuclear exosome targeting complex. Mol. Cell 19, 624-637 (2011).
35. Younis, I., et al. Minor introns are embedded molecular switches regulated by highly unstable U6atac snRNA. Elife 2, e00780 (2013).
36. Patel, A. A., McCarthy, M. & Steitz, J. A. The splicing of U12-type introns can be a rate-limiting step in gene expression. EMBO J. 15, 3804-3815 (2002).
37. Pessa, H. K., Ruokolainen, A. & Frilander, M. J. The abundance of the spliceosomal snRNPs is not limiting the splicing of U12-type introns. RNA 12, 1883-1892 (2006).
38. Niemelä, E. H., et al. Global analysis of the nuclear processing of transcripts with unspliced U12-type introns by the exosome. Nucleic Acids Res. 42, 7358-7369 (2014).
39. Drmanac, R., et al. Human genome sequencing using unchained base reads on self-assembling DNA nanoarrays. Science 327, 78-81 (2010).
40. Carnevali, P., Baccash, J., Halpern, A. L., Nazarenko, I. & Nilsen, G. B. Computational techniques for human genome resequencing using mated gapped reads. J. Comput. Biol. 19, 279-292 (2012).
41. Wang, K., Li, M. & Hakonarson, H. ANNOVAR: functional annotation of genetic variants from next-generation sequencing data. Nucleic Acids Res. 38, e164 (2010).
42. 1000 Genomes Project Consortium, et al. A map of human genome variation from population-scale sequencing. Nature 467, 1061-1073 (2010).
43. Tennessen, J. A., et al. Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science 337, 64-69 (2012).
44. Pollard, K. S., Hubisz, M. J., Rosenbloom, K. R. & Siepel, A. Detection of nonneutral substitution rates on mammalian phylogenies. Genome Res. 20, 110-121 (2010).
45. Ng, P. C. & Henikoff, S. Predicting deleterious amino acid substitutions. Genome Res. 11, 863-874 (2001).
46. Adzhubei, I. A., Schmidt, S., Peshkin, L., Ramensky, V. E. & Gerasimova, A. A method and server for predicting damaging missense mutations. Nat. Methods 7, 248-249 (2010).
47. Reva, B., Antipin, Y. & Sander, C. Predicting the functional impact of protein mutations: application to cancer genomics. Nucleic Acids Res. 39, e118 (2011).
48. Kircher, M., et al. A general framework for estimating the relative pathogenicity of human genetic variants. Nat. Genet. 46, 310-315 (2014).
49. Robinson, P. N., et al. The human phenotype ontology: a tool for annotating and analyzing human hereditary disease. Am. J. Hum. Genet. 83, 610-615 (2008).
50. Solomon, B. D., Nguyen, A. D., Bear, K. A. & Wolfsberg, T. G. Clinical genomic database. Proc. Natl Acad. Sci. USA 110, 9851-9855.
51. MacDonald, J. R., Ziman, R., Yuen, R. K., Feuk, L. & Scherer, S. W. The Database of Genomic Variants: a curated collection of structural variation in the human genome. Nucleic Acids Res. 42, D986-D992 (2014).
52. Alioto, T. S. U12DB: a database of orthologous U12-type spliceosomal introns. Nucleic Acids Res. 35, D110-D115 (2007).
53. Stormo, G. D. DNA binding sites: representation and discovery. Bioinformatics 16, 16-23 (2000).
54. Bailey, T. L. & Elkan, C. Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc. Int. Conf. Intell. Syst. Mol. Biol. 2, 28-36 (1994).
55. Irimia, M., et al. A highly conserved program of neuronal microexons is misregulated in autistic brains. Cell 159, 1511-1523 (2014).
56. Barbosa-Morais, N. L., et al. The evolutionary landscape of alternative splicing in vertebrate species. Science 338, 1587-1593 (2012).
57. Labbe, R. M., et al. A comparative transcriptomic analysis reveals conserved features of stem cell pluripotency in planarians and mammals. Stem Cells 30, 1734-1745 (2012).
58. Trapnell, C., Pachter, L. & Salzberg, S. L. TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25, 1105-1111 (2009).
59. Anders, S., Pyl, P. T. & Huber, W. HTSeq-a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166-169 (2015).
60. Liu, S., et al. Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP. Science 316, 115-120 (2007).
61. Liu, S., Ghalei, H., Lührmann, R. &Wahl, M. C. Structural basis for the dual U4 and U4atac snRNA-binding specificity of spliceosomal protein hPrp31. RNA 17, 1655-1663 (2011).