UBE2A deficiency syndrome: Mild to severe intellectual disability accompanied by seizures, absent speech, urogenital, and skin anomalies in male patients.
de Leeuw, Nicole; BULK, Saskia; Green, Andrewet al.
2010 • In American Journal of Medical Genetics. Part A, 152A (12), p. 3084-90
[en] We describe three patients with a comparable deletion encompassing SLC25A43, SLC25A5, CXorf56, UBE2A, NKRF, and two non-coding RNA genes, U1 and LOC100303728. Moderate to severe intellectual disability (ID), psychomotor retardation, severely impaired/absent speech, seizures, and urogenital anomalies were present in all three patients. Facial dysmorphisms include ocular hypertelorism, synophrys, and a depressed nasal bridge. These clinical features overlap with those described in two patients from a family with a similar deletion at Xq24 that also includes UBE2A, and in several patients of Brazilian and Polish families with point mutations in UBE2A. Notably, all five patients with an Xq24 deletion have ventricular septal defects that are not present in patients with a point mutation, which might be attributed to the deletion of SLC25A5. Taken together, the UBE2A deficiency syndrome in male patients with a mutation in or a deletion of UBE2A is characterized by ID, absent speech, seizures, urogenital anomalies, frequently including a small penis, and skin abnormalities, which include generalized hirsutism, low posterior hairline, myxedematous appearance, widely spaced nipples, and hair whorls. Facial dysmorphisms include a wide face, a depressed nasal bridge, a large mouth with downturned corners, thin vermilion, and a short, broad neck.
Disciplines :
Genetics & genetic processes
Author, co-author :
de Leeuw, Nicole
BULK, Saskia ; Centre Hospitalier Universitaire de Liège - CHU > Génétique
Green, Andrew
Jaeckle-Santos, Lane
Baker, Linda A.
Zinn, Andrew R.
Kleefstra, Tjitske
van der Smagt, Jasper J.
Vianne Morgante, Angela Maria
de Vries, Bert B. A.
van Bokhoven, Hans
de Brouwer, Arjan P. M.
Language :
English
Title :
UBE2A deficiency syndrome: Mild to severe intellectual disability accompanied by seizures, absent speech, urogenital, and skin anomalies in male patients.
Allen RC, Zoghbi HY, Moseley AB, Rosenblatt HM, Belmont JW. 1992. Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. Am J Hum Genet 51: 1229-1239.
Budny B, Badura-Stronka M, Materna-Kiryluk A, Tzschach A, Raynaud M, Latos-Bielenska A, Ropers H. 2010. Novel missense mutations in the ubiquitination-related gene UBE2A cause a recognizable X-linked mental retardation syndrome. Clin Genet 77: 541-551.
Dreikhausen U, Hiebenthal-Millow K, Bartels M, Resch K, Nourbakhsh M. 2005. NF-kappaB-repressing factor inhibits elongation of human immunodeficiency virus type 1 transcription by DRB sensitivity-inducing factor. Mol Cell Biol 25: 7473-7483.
Ellison JW, Li X, Francke U, Shapiro LJ. 1996. Rapid evolution of human pseudoautosomal genes and their mouse homologs. Mamm Genome 7: 25-30.
Feng X, Guo Z, Nourbakhsh M, Hauser H, Ganster R, Shao L, Geller DA. 2002. Identification of a negative response element in the human inducible nitric-oxide synthase (hiNOS) promoter: The role of NF-kappa B-repressing factor (NRF) in basal repression of the hiNOS gene. Proc Natl Acad Sci USA 99: 14212-14217.
Froese N, Schwarzer M, Niedick I, Frischmann U, Koster M, Kroger A, Mueller PP, Nourbakhsh M, Pasche B, Reimann J, Staeheli P, Hauser H. 2006. Innate immune responses in NF-kappaB-repressing factor-deficient mice. Mol Cell Biol 26: 293-302.
Haitina T, Lindblom J, Renstrom T, Fredriksson R. 2006. Fourteen novel human members of mitochondrial solute carrier family 25 (SLC25) widely expressed in the central nervous system. Genomics 88: 779-790.
Honda S, Orii KO, Kobayashi J, Hayashi S, Imamura A, Imoto I, Nakagawa E, Goto YI, Inazawa J. 2010. Novel deletion at Xq24 including the UBE2A gene in a patient with X-linked mental retardation. J Hum Genet 55: 244-247.
Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402-408.
Lugtenberg D, de Brouwer AP, Kleefstra T, Oudakker AR, Frints SG, Schrander-Stumpel CT, Fryns JP, Jensen LR, Chelly J, Moraine C, Turner G, Veltman JA, Hamel BC, de Vries BB, van Bokhoven H, Yntema HG. 2006. Chromosomal copy number changes in patients with non-syndromic X linked mental retardation detected by array CGH. J Med Genet 43: 362-370.
Lunardi J, Hurko O, Engel WK, Attardi G. 1992. The multiple ADP/ATP translocase genes are differentially expressed during human muscle development. J Biol Chem 267: 15267-15270.
Marcelis CL, Hol FA, Graham GE, Rieu PN, Kellermayer R, Meijer RP, Lugtenberg D, Scheffer H, van Bokhoven H, Brunner HG, de Brouwer AP. 2008. Genotype-phenotype correlations in MYCN-related Feingold syndrome. Hum Mutat 29: 1125-1132.
Miller SA, Dykes DD, Polesky HF. 1988. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16: 1215.
Nannya Y, Sanada M, Nakazaki K, Hosoya N, Wang L, Hangaishi A, Kurokawa M, Chiba S, Bailey DK, Kennedy GC, Ogawa S. 2005. A robust algorithm for copy number detection using high-density oligonucleotide single nucleotide polymorphism genotyping arrays. Cancer Res 65: 6071-6079.
Nascimento RM, Otto PA, de Brouwer AP, Vianna-Morgante AM. 2006. UBE2A, which encodes a ubiquitin-conjugating enzyme, is mutated in a novel X-linked mental retardation syndrome. Am J Hum Genet 79: 549-555.
Nourbakhsh M, Hauser H. 1999. Constitutive silencing of IFN-beta promoter is mediated by NRF (NF-kappaB-repressing factor), a nuclear inhibitor of NF-kappaB. EMBO J 18: 6415-6425.
Nourbakhsh M, Kalble S, Dorrie A, Hauser H, Resch K, Kracht M. 2001. The NF-kappa b repressing factor is involved in basal repression and interleukin (IL)-1-induced activation of IL-8 transcription by binding to a conserved NF-kappa b-flanking sequence element. J Biol Chem 276: 4501-4508.
Palmieri F. 2004. The mitochondrial transporter family (SLC25): Physiological and pathological implications. Pflugers Arch 447: 689-709.
Pfaffl MW. 2001. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29: e45.
Raponi M, Baralle D. 2008. Can donor splice site recognition occur without the involvement of U1 snRNP? Biochem Soc Trans 36: 548-550.
Rozen S, Skaletsky H. 2000. Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132: 365-386.
Stepien G, Torroni A, Chung AB, Hodge JA, Wallace DC. 1992. Differential expression of adenine nucleotide translocator isoforms in mammalian tissues and during muscle cell differentiation. J Biol Chem 267: 14592-14597.
Van Esch H, Bauters M, Ignatius J, Jansen M, Raynaud M, Hollanders K, Lugtenberg D, Bienvenu T, Jensen LR, Gecz J, Moraine C, Marynen P, Fryns JP, Froyen G. 2005. Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Am J Hum Genet 77: 442-453.
Wei F, Cheng S, Badie N, Elder F, Scott C Jr, Nicholson L, Ross JL, Zinn AR. 2001. A man who inherited his SRY gene and Leri-Weill dyschondrosteosis from his mother and neurofibromatosis type 1 from his father. Am J Med Genet 102: 353-358.
Ye Y, Rape M. 2009. Building ubiquitin chains: E2 enzymes at work. Nat Rev Mol Cell Biol 10: 755-764.
Zhang J, Feuk L, Duggan GE, Khaja R, Scherer SW. 2006. Development of bioinformatics resources for display and analysis of copy number and other structural variants in the human genome. Cytogenet Genome Res 115: 205-214.
Zhang Y, Luoh SM, Hon LS, Baertsch R, Wood WI, Zhang Z. 2007. GeneHub-GEPIS: Digital expression profiling for normal and cancer tissues based on an integrated gene database. Nucleic Acids Res 35: W152-W158.
