Heterozygous HNRNPU variants cause early onset epilepsy and severe intellectual disability

Human Genetics

Volumn 136, Issue 7, 2017, Pages 821-834

  Bramswig, Nuria C ^a   Lüdecke, Hermann Josef ^a,b   Hamdan, Fadi F ^c   Altmüller, Janine ^d   Beleggia, Filippo ^b,e   Elcioglu, Nursel H ^f,g   Freyer, Catharine ^h   Gerkes, Erica H ⁱ   Demirkol, Yasemin Kendir ^f   Knupp, Kelly G ^j   Kuechler, Alma ^a   Li, Yun ^k   Lowenstein, Daniel H ^h   Michaud, Jacques L ^c,l   Park, Kristen ^j   Stegmann, Alexander P A ^m   Veenstra Knol, Hermine E ⁱ   Wieland, Thomas ^n,o   Wollnik, Bernd ^k   Engels, Hartmut ^p   Strom, Tim M ^n,o   Kleefstra, Tjitske ^q   Wieczorek, Dagmar ^a,b   more..

^a UNIVERSITY HOSPITAL ESSEN   (Germany)

^b UNIVERSITY HOSPITAL DÜSSELDORF   (Germany)

^c UNIVERSITY OF MONTREAL   (Canada)

^d UNIVERSITY OF COLOGNE   (Germany)

^e UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

^f MARMARA UNIVERSITY SCHOOL OF MEDICINE   (Turkey)

^g EASTERN MEDITERRANEAN UNIVERSITY   (Turkey)

^h UNIVERSITY OF CALIFORNIA   (United States)

ⁱ UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^j UNIVERSITY OF COLORADO   (United States)

^k UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^l UNIVERSITÉ DE MONTRÉAL   (Canada)

^m MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

ⁿ INSTITUTE OF EPIDEMIOLOGY   (Germany)

^o TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^p UNIVERSITY OF BONN   (Germany)

^q RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CARBAMAZEPINE; CLOBAZAM; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN U; LAMOTRIGINE; PHENOBARBITAL; RUFINAMIDE; TOPIRAMATE; SAF-A PROTEIN, HUMAN; SMALL NUCLEAR RIBONUCLEOPROTEIN;

ABDOMINAL AORTA; AORTIC DISEASE; ARTICLE; ASTIGMATISM; AUTISM; BRAIN ATROPHY; CEREBELLUM VERMIS; CLINICAL FEATURE; COMPULSION; CONTRACTURE; CONTROLLED STUDY; CORPUS CALLOSUM; CRYPTORCHISM; DISEASE SEVERITY; DIVERGENT STRABISMUS; ECHOCARDIOGRAPHY; EDEMA; ELECTROENCEPHALOGRAM; EPILEPSY; EXON; FACIES; FAILURE TO THRIVE; FRAMESHIFT MUTATION; GENETIC VARIABILITY; HEART ATRIUM SEPTUM DEFECT; HETEROZYGOTE; HUMAN; HYPERMETROPIA; HYPERTELORISM; HYPOSPADIAS; INTELLECTUAL IMPAIRMENT; INTRON; KIDNEY AGENESIS; LONG PHILTRUM; MAJOR CLINICAL STUDY; MICROCEPHALY; MUSCLE HYPOTONIA; MYOPIA; NONSENSE MUTATION; NUCLEAR MAGNETIC RESONANCE IMAGING; NYSTAGMUS; PERCEPTION DEAFNESS; PERINATAL ASPHYXIA; PHENOTYPE; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; SHORT NOSE; SPEECH DISORDER; SUBDURAL HEMATOMA; TONIC CLONIC SEIZURE; VAGUS NERVE STIMULATION; ABNORMALITIES; CENTRAL NERVOUS SYSTEM; CHROMOSOME 1; CHROMOSOME DELETION; CORPUS CALLOSUM AGENESIS; FEMALE; GENETIC VARIATION; GENETICS; INFANT; INTELLECTUAL DISABILITY; KIDNEY; MALE; ONSET AGE; PATHOLOGY; RNA SPLICING; SEIZURES;

AGE OF ONSET; AGENESIS OF CORPUS CALLOSUM; CENTRAL NERVOUS SYSTEM; CHROMOSOME DELETION; CHROMOSOMES, HUMAN, PAIR 1; EPILEPSY; FEMALE; GENETIC VARIATION; HETEROGENEOUS-NUCLEAR RIBONUCLEOPROTEIN U; HETEROZYGOTE; HUMANS; INFANT; INTELLECTUAL DISABILITY; KIDNEY; MALE; MICROCEPHALY; MUSCLE HYPOTONIA; PHENOTYPE; RIBONUCLEOPROTEINS, SMALL NUCLEAR; RNA SPLICING; SEIZURES;

EID: 85017177644     PISSN: 03406717     EISSN: 14321203     Source Type: Journal    
DOI: 10.1007/s00439-017-1795-6     Document Type: Article

References (30)

1. Allen AS et al (2013) De novo mutations in epileptic encephalopathies. Nature 501:217–221. doi:10.1038/nature12439
2. Ballif BC et al (2012) High-resolution array CGH defines critical regions and candidate genes for microcephaly, abnormalities of the corpus callosum, and seizure phenotypes in patients with microdeletions of 1q43q44. Hum Genet 131:145–156. doi:10.1007/s00439-011-1073-y
3. Boland E et al (2007) Mapping of deletion and translocation breakpoints in 1q44 implicates the serine/threonine kinase AKT3 in postnatal microcephaly and agenesis of the corpus callosum. Am J Hum Genet 81:292–303
4. Bramswig NC et al (2015) Exome sequencing unravels unexpected differential diagnoses in individuals with the tentative diagnosis of Coffin-Siris and Nicolaides-Baraitser syndromes. Hum Genet 134:553–568. doi:10.1007/s00439-015-1535-8
5. Caliebe A et al (2010) Four patients with speech delay, seizures and variable corpus callosum thickness sharing a 0.440 Mb deletion in region 1q44 containing the HNRPU gene. Eur J Med Genet 53:179–185. doi:10.1016/j.ejmg.2010.04.001
6. Carvill GL et al (2013) Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1. Nat Genet 45:825–830. doi:10.1038/ng.2646
7. de Kovel CG et al (2016) Targeted sequencing of 351 candidate genes for epileptic encephalopathy in a large cohort of patients Mol Genet. Genomic Med 4:568–580. doi:10.1002/mgg3.235
8. de Ligt J et al (2012) Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med 367:1921–1929. doi:10.1056/NEJMoa1206524
9. Depienne C et al (2017) Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU. Hum Genet. doi:10.1007/s00439-017-1772-0
10. Fromer M et al (2012) Discovery and statistical genotyping of copy-number variation from whole-exome sequencing depth. Am J Hum Genet 91:597–607. doi:10.1016/j.ajhg.2012.08.005
11. Fu XD, Ares M Jr (2014) Context-dependent control of alternative splicing by RNA-binding proteins. Nat Rev Genet 15:689–701. doi:10.1038/nrg3778
12. Geuens T, Bouhy D, Timmerman V (2016) The hnRNP family: insights into their role in health and disease. Hum Genet 135:851–867. doi:10.1007/s00439-016-1683-5
13. Hamdan FF et al (2014) De novo mutations in moderate or severe intellectual disability. PLoS Genet 10:e1004772. doi:10.1371/journal.pgen.1004772
14. Hill AD, Chang BS, Hill RS, Garraway LA, Bodell A, Sellers WR, Walsh CA (2007) A 2-Mb critical region implicated in the microcephaly associated with terminal 1q deletion syndrome. Am J Med Genet A 143A:1692–1698. doi:10.1002/ajmg.a.31776
15. Hussain MS et al (2014) Mutations in CKAP2L, the human homolog of the mouse Radmis gene, cause Filippi syndrome. Am J Hum Genet 95:622–632. doi:10.1016/j.ajhg.2014.10.008
16. Jiang Y, Oldridge DA, Diskin SJ, Zhang NR (2015) CODEX: a normalization and copy number variation detection method for whole exome sequencing. Nucleic Acids Res 43:e39. doi:10.1093/nar/gku1363
17. Keupp K et al (2013) Mutations in WNT1 cause different forms of bone fragility. Am J Hum Genet 92:565–574. doi:10.1016/j.ajhg.2013.02.010
18. Lehalle D, Wieczorek D, Zechi-Ceide RM, Passos-Bueno MR, Lyonnet S, Amiel J, Gordon CT (2015) A review of craniofacial disorders caused by spliceosomal defects. Clin Genet 88:405–415. doi:10.1111/cge.12596
19. Monroe GR et al (2016) Effectiveness of whole-exome sequencing and costs of the traditional diagnostic trajectory in children with intellectual disability. Genet Med 18:949–956. doi:10.1038/gim.2015.200
20. Nagamani SC et al (2012) Delineation of a deletion region critical for corpus callosal abnormalities in chromosome 1q43-q44. Eur J Hum Genet 20:176–179. doi:10.1038/ejhg.2011.171
21. Need AC et al (2012) Clinical application of exome sequencing in undiagnosed genetic conditions. J Med Genet 49:353–361. doi:10.1136/jmedgenet-2012-100819
22. Park DH et al (2014) Activation of neuronal gene expression by the JMJD3 demethylase is required for postnatal and adult brain neurogenesis. Cell Rep 8:1290–1299. doi:10.1016/j.celrep.2014.07.060
23. Perfetto L, Gherardini PF, Davey NE, Diella F, Helmer-Citterich M, Cesareni G (2013) Exploring the diversity of SPRY/B30.2-mediated interactions. Trends Biochem Sci 38:38–46. doi:10.1016/j.tibs.2012.10.001
24. Poot MaK MJ (2013) Antisense May Make Sense of 1q44 Deletions. Seizures, and HNRNPU Am J Med Genet Part A 161A:910–912
25. Roshon MJ, Ruley HE (2005) Hypomorphic mutation in hnRNP U results in post-implantation lethality. Transgenic Res 14:179–192
26. Thierry G et al (2012) Molecular characterization of 1q44 microdeletion in 11 patients reveals three candidate genes for intellectual disability and seizures. Am J Med Genet A 158A:1633–1640. doi:10.1002/ajmg.a.35423
27. van Bon BW et al (2008) Clinical and molecular characteristics of 1qter microdeletion syndrome: delineating a critical region for corpus callosum agenesis/hypogenesis. J Med Genet 45:346–354. doi:10.1136/jmg.2007.055830
28. Wang GS, Cooper TA (2007) Splicing in disease: disruption of the splicing code and the decoding machinery. Nat Rev Genet 8:749–761
29. Xiao R et al (2012) Nuclear matrix factor hnRNP U/SAF-A exerts a global control of alternative splicing by regulating U2 snRNP maturation. Mol Cell 45:656–668. doi:10.1016/j.molcel.2012.01.009
30. Ye J et al (2015) hnRNP U protein is required for normal pre-mRNA splicing and postnatal heart development and function. Proc Natl Acad Sci USA 112:E3020–E3029. doi:10.1073/pnas.1508461112