Interpretation of clinical relevance of X-chromosome copy number variations identified in a large cohort of individuals with cognitive disorders and/or congenital anomalies

European Journal of Medical Genetics

Volumn 55, Issue 11, 2012, Pages 586-598

  Willemsen, Marjolein H ^a   de Leeuw, Nicole ^a   de Brouwer, Arjan P M ^a   Pfundt, Rolph ^a   Hehir Kwa, Jayne Y ^a   Yntema, Helger G ^a   Nillesen, Willy M ^a   de Vries, Bert B A ^a   van Bokhoven, Hans ^a   Kleefstra, Tjitske ^a  

^a RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

Autism; Clinical interpretation; Copy number variation; Intellectual disability; X chromosome; X linked

Indexed keywords

ADULT; ARTICLE; COGNITIVE DEFECT; CONGENITAL MALFORMATION; COPY NUMBER VARIATION; DATA BASE; DIAGNOSTIC TEST; FEMALE; GENETIC ASSOCIATION; HUMAN; LABORATORY; MAJOR CLINICAL STUDY; MALE; MEDICAL LITERATURE; PREVALENCE; X CHROMOSOME;

ADOLESCENT; CHILD; CHILD, PRESCHOOL; CHROMOSOMES, HUMAN, X; COGNITION DISORDERS; COHORT STUDIES; CONGENITAL ABNORMALITIES; DNA COPY NUMBER VARIATIONS; FEMALE; GENOME, HUMAN; HUMANS; INFANT; INTELLECTUAL DISABILITY; MALE; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS;

EID: 84867139107     PISSN: 17697212     EISSN: 18780849     Source Type: Journal    
DOI: 10.1016/j.ejmg.2012.05.001     Document Type: Article

References (79)

1. American Association on Intellectual and Developmental Disabilities Intellectual Disability: Definition, Classification, and Systems of Support 2010, American Association on Intellectual and Developmental Disabilities, Washington DC. eleventh ed.
2. Kogan M.D., Blumberg S.J., Schieve L.A., Boyle C.A., Perrin J.M., Ghandour R.M., Singh G.K., Strickland B.B., Trevathan E., van Dyck P.C. Prevalence of parent-reported diagnosis of autism spectrum disorder among children in the US, 2007. Pediatrics 2009, 124(5):1395-1403.
3. Mandel J.L., Chelly J. Monogenic X-linked mental retardation: is it as frequent as currently estimated? The paradox of the ARX (Aristaless X) mutations. Eur. J. Hum. Genet. 2004, 12(9):689-693.
4. Ropers H.H. X-linked mental retardation: many genes for a complex disorder. Curr. Opin. Genet. Dev. 2006, 16(3):260-269.
5. Curry C.J., Stevenson R.E., Aughton D., Byrne J., Carey J.C., Cassidy S., Cunniff C., Graham J.M., Jones M.C., Kaback M.M., Moeschler J., Schaefer G.B., et al. Evaluation of mental retardation: recommendations of a Consensus Conference: American College of Medical Genetics. Am. J. Med. Genet. 1997, 72:468-477.
6. Leonard H., Wen X. The epidemiology of mental retardation: challenges and opportunities in the new millennium. Ment. Retard. Dev. Disabil. Res. Rev. 2002, 8(3):117-134.
7. Moog U. The outcome of diagnostic studies on the etiology of mental retardation: considerations on the classification of the causes. Am. J. Med. Genet. A 2005, 137(2):228-231.
8. Rauch A., Hoyer J., Guth S., Zweier C., Kraus C., Becker C., Zenker M., Hüffmeier U., Thiel C., Rüschendorf F., Nürnberg P., Reis A., et al. Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation. Am. J. Med. Genet. A 2006, 140(19):2063-2074.
9. Van Karnebeek C.D., Scheper F.Y., Abeling N.G., Alders M., Barth P.G., Hoovers J.M., Koevoets C., Wanders R.J., Hennekam R.C. Etiology of mental retardation in children referred to a tertiary care center: a prospective study. Am. J. Ment. Retard. 2005, 110(4):253-267.
10. Miles J.H. Autism spectrum disorders-a genetics review. Genet. Med. 2011, 13(4):278-294.
11. Morrow E.M. Genomic copy number variation in disorders of cognitive development. J. Am. Acad. Child. Adolesc. Psychiatry 2010, 49(11):1091-1104.
12. Fan Y.S., Jayakar P., Zhu H., Barbouth D., Sacharow S., Morales A., Carver V., Benke P., Mundy P., Elsas L.J. Detection of pathogenic gene copy number variations in patients with mental retardation by genome-wide oligonucleotide array comparative genomic hybridization. Hum. Mutat. 2007, 28(11):124-132.
13. Friedman J.M., Adam S., Arbour L., Armstrong L., Baross A., Birch P., Boerkoel C., Chan S., Chai D., Delaney A.D., Flibotte S., Gibson W.T., et al. Detection of pathogenic copy number variants in children with idiopathic intellectual disability using 500 K SNP array genomic hybridization. BMC Genomics 2009, 10:526.
14. Koolen D.A., Pfundt R., de Leeuw N., Hehir-Kwa J.Y., Nillesen W.M., Neefs I., Scheltinga I., Sistermans E., Smeets D., Brunner H.G., van Kessel A.G., Veltman J.A., et al. Genomic microarrays in mental retardation: a practical workflow for diagnostic applications. Hum. Mutat. 2009, 30(3):283-292.
15. Aradhya S., Manning M.A., Splendore A., Cherry A.M. Whole-genome array-CGH identifies novel contiguous gene deletions and duplications associated with developmental delay, mental retardation, and dysmorphic features. Am. J. Med. Genet. A 2007, 143A(13):1431-1441.
16. Bruno D.L., Ganesamoorthy D., Schoumans J., Bankier A., Coman D., Delatycki M., Gardner R.J., Hunter M., James P.A., Kannu P., McGillivray G., Pachter N., et al. Detection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice. J. Med. Genet. 2009, 46(2):123-131.
17. Buysse K., Delle Chiaie B., Van Coster R., Loeys B., De Paepe A., Mortier G., Speleman F., Menten B. Challenges for CNV interpretation in clinical molecular karyotyping: lessons learned from a 1001 sample experience. Eur. J. Med. Genet. 2009, 52(6):398-403.
18. Jaillard S., Drunat S., Bendavid C., Aboura A., Etcheverry A., Journel H., Delahaye A., Pasquier L., Bonneau D., Toutain A., Burglen L., Guichet A., et al. Identification of gene copy number variations in patients with mental retardation using array-CGH: novel syndromes in a large French series. Eur. J. Med. Genet. 2010, 53(2):66-75.
19. Engels H., Brockschmidt A., Hoischen A., Landwehr C., Bosse K., Walldorf C., Toedt G., Radlwimmer B., Propping P., Lichter P., Weber R.G. DNA microarray analysis identifies candidate regions and genes in unexplained mental retardation. Neurology 2007, 68(10):743-750.
20. Hoyer J., Dreweke A., Becker C., Göhring I., Thiel C.T., Peippo M.M., Rauch R., Hofbeck M., Trautmann U., Zweier C., Zenker M., Hüffmeier U., et al. Molecular karyotyping in patients with mental retardation using 100 K single-nucleotide polymorphism arrays. J. Med. Genet. 2007, 44(10):629-636.
21. Krepischi-Santos A.C.V., Vianna-Morgante A.M., Jehee F.S., Passos-Bueno M.R., Knijnenburg J., Szuhai K., Sloos W., Mazzeu J.F., Kok F., Cheroki C., Otto P.A., Mingroni-Netto R.C., et al. Whole-genome array-CGH screening in undiagnosed syndromic patients: old syndromes revisited and new alterations. Cytogenet. Genome Res. 2006, 115:254-261.
22. McMullan D.J., Bonin M., Hehir-Kwa J.Y., de Vries B.B., Dufke A., Rattenberry E., Steehouwer M., Moruz L., Pfundt R., de Leeuw N., Riess A., Altug-Teber O., et al. Molecular karyotyping of patients with unexplained mental retardation by SNP arrays: a multicenter study. Hum. Mutat. 2009, 30(7):1082-1092.
23. Menten B., Maas N., Thienpont B., Buysse K., Vandesompele J., Melotte C., de Ravel T., Van Vooren S., Balikova I., Backx L., Janssens S., De Paepe A., et al. Emerging patterns of cryptic chromosomal imbalance in patients with idiopathic mental retardation and multiple congenital anomalies: a new series of 140 patients and review of published reports. J. Med. Genet. 2006, 43:625-633.
24. Miyake N., Shimokawa O., Harada N., Sosonkina N., Okubo A., Kawara H., Okamoto N., Kurosawa K., Kawame H., Iwakoshi M., Kosho T., Fukushima Y., et al. BAC array CGH reveals genomic aberrations in idiopathic mental retardation. Am. J. Med. Genet. A 2006, 140(3):205-211.
25. Rosenberg C., Knijnenburg J., Bakker E., Vianna-Morgante A.M., Sloos W., Otto P.A., Kriek M., Hansson K., Krepischi-Santos A.C., Fiegler H., Carter N.P., Bijlsma E.K., et al. Array-CGH detection of micro rearrangements in mentally retarded individuals: clinical significance of imbalances present both in affected children and normal parents. J. Med. Genet. 2006, 43(2):180-186.
26. Schoumans J., Ruivenkamp C., Holmberg E., Kyllerman M., Anderlid B.M., Nordenskjöld M. Detection of chromosomal imbalances in children with idiopathic mental retardation by array based comparative genomic hybridisation (array-CGH). J. Med. Genet. 2005, 42(9):699-705.
27. Shaw-Smith C., Redon R., Rickman L., Rio M., Willatt L., Fiegler H., Firth H., Sanlaville D., Winter R., Colleaux L., Bobrow M., Carter N.P. Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features. J. Med. Genet. 2004, 41(4):241-248.
28. Tyson C., Harvard C., Locker R., Friedman J.M., Langlois S., Lewis M.E., Van Allen M., Somerville M., Arbour L., Clarke L., McGilivray B., Yong S.L., et al. Submicroscopic deletions and duplications in individuals with intellectual disability detected by array-CGH. Am. J. Med. Genet. A 2005, 139(3):173-185.
29. Thuresson A.C., Bondeson M.L., Edeby C., Ellis P., Langford C., Dumanski J.P., Annerén G. Whole-genome array-CGH for detection of submicroscopic chromosomal imbalances in children with mental retardation. Cytogenet. Genome Res. 2007, 118(1):1-7.
30. Wagenstaller J., Spranger S., Lorenz-Depiereux B., Kazmierczak B., Nathrath M., Wahl D., Heye B., Glaser D., Liebscher V., Meitinger T., Strom T.M. Copy-number variations measured by single-nucleotide-polymorphism oligonucleotide arrays in patients with mental retardation. Am. J. Hum. Genet. 2007, 81(4):768-779.
31. Tucker T., Montpetit A., Chai D., Chan S., Chénier S., Coe B.P., Delaney A., Eydoux P., Lam W.L., Langlois S., Lemyre E., Marra M., et al. Comparison of genome-wide array genomic hybridization platforms for the detection of copy number variants in idiopathic mental retardation. BMC Med. Genomics 2011, 4:25.
32. Xiang B., Zhu H., Shen Y., Miller D.T., Lu K., Hu X., Andersson H.C., Narumanchi T.M., Wang Y., Martinez J.E., Wu B.L., Li P., et al. Genome-wide oligonucleotide array comparative genomic hybridization for etiological diagnosis of mental retardation: a multicenter experience of 1499 clinical cases. J. Mol. Diagn. 2010, 12(2):204-212.
33. Hayashi S., Imoto I., Aizu Y., Okamoto N., Mizuno S., Kurosawa K., Okamoto N., Honda S., Araki S., Mizutani S., Numabe H., Saitoh S., et al. Clinical application of array-based comparative genomic hybridization by two-stage screening for 536 patients with mental retardation and multiple congenital anomalies. J. Hum. Genet. 2011, 56(2):110-124.
34. Bauters M., Weuts A., Vandewalle J., Nevelsteen J., Marynen P., Van Esch H., Froyen G. Detection and validation of copy number variation in X-linked mental retardation. Cytogenet. Genome Res. 2008, 123(1-4):44-53.
35. Froyen G., Van Esch H., Bauters M., Hollanders K., Frints S.G.M., Vermeesch J.R., Devriendt K., Fryns J., Marynen P. Detection of genomic copy number changes in patients with idiopathic mental retardation by high-resolution X-array-CGH: important role for increased gene dosage of XLMR genes. Hum. Mutat. 2007, 28(10):1034-1042.
36. Lugtenberg D., de Brouwer A.P., Kleefstra T., Oudakker A.R., Frints S.G., Schrander-Stumpel C.T., Fryns J.P., Jensen L.R., Chelly J., Moraine C., Turner G., Veltman J.A., et al. Chromosomal copy number changes in patients with non-syndromic X linked mental retardation detected by array CGH. J. Med. Genet. 2006, 43(4):362-370.
37. Lugtenberg D., Veltman J.A., van Bokhoven H. High-resolution genomic microarrays for X-linked mental retardation. Genet. Med. 2007, 9(9):560-565.
38. Madrigal I., Rodriguez-Revenga L., Armengol L., Gonzalez E., Rodriguez B., Badenas C., Sanchez A., Martinez F., Guitart M., Fernandez I., Arranz J.A., Tejada M., et al. X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation. BMC Genomics 2007, 8:443.
39. Veltman J.A., Yntema H.G., Lugtenberg D., Arts H., Briault S., Huys E.H., Osoegawa K., de Jong P., Brunner H.G., Geurts van Kessel A., van Bokhoven H., Schoenmakers E.F. High resolution profiling of X chromosomal aberrations by array comparative genomic hybridisation. J. Med. Genet. 2004, 41(6):425-432.
40. Whibley A.C., Plagnol V., Tarpey P.S., Abidi F., Fullston T., Choma M.K., Boucher C.A., Shepherd L., Willatt L., Parkin G., Smith R., Futreal P.A., et al. Fine-scale survey of X chromosome copy number variants and indels underlying intellectual disability. Am. J. Hum. Genet. 2010, 87(2):173-188.
41. Lugtenberg D., Yntema H.G., Banning M.J., Oudakker A.R., Firth H.V., Willatt L., Raynaud M., Kleefstra T., Fryns J.P., Ropers H.H., Chelly J., Moraine C., et al. A new Kruppel-associated box-containing zinc-finger gene involved in nonsyndromic X-linked mental retardation. Am. J. Hum. Genet. 2006, 78(2):265-278.
42. Van Esch H., Bauters M., Ignatius J., Jansen M., Raynaud M., Hollanders K., Lugtenberg D., Bienvenu T., Jensen L.R., Gecz J., Moraine C., Marynen P., et al. Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males. Am. J. Hum. Genet. 2005, 77(3):442-453.
43. Marshall C.R., Noor A., Vincent J.B., Lionel A.C., Feuk L., Skaug J., Shago M., Moessner R., Pinto D., Ren Y., Thiruvahindrapduram B., Fiebig A., et al. Structural variation of chromosomes in autism spectrum disorder. Am. J. Hum. Genet. 2008, 82(2):477-488.
44. Glessner J.T., Wang K., Cai G., Korvatska O., Kim C.E., Wood S., Zhang H., Estes A., Brune C.W., Bradfield J.P., Imielinski M., Frackelton E.C., et al. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 2009, 459(7246):569-573.
45. Iafrate A.J., Feuk L., Rivera M.N., Listewnik M.L., Donahoe P.K., Qi Y., Scherer S.W., Lee C. Detection of large-scale variation in the human genome. Nat. Genet. 2004, 36(9):949-951.
46. Pinto D., Marshall C., Feuk L., Scherer S.W. Copy-number variation in control population cohorts. Hum. Mol. Genet. 2007, 16(2):R168-R173.
47. Redon R., Ishikawa S., Fitch K.R., Feuk L., Perry G.H., Andrews T.D., Fiegler H., Shapero M.H., Carson A.R., Chen W., Cho E.K., Dallaire S., et al. Global variation in copy number in the human genome. Nature 2006, 444(7118):444-454.
48. Nannya Y., Sanada M., Nakazaki K., Hosoya N., Wang L., Hangaishi A., Kurokawa M., Chiba S., Bailey D.K., Kennedy G.C., Ogawa S. A robust algorithm for copy number detection using high-density oligonucleotide single nucleotide polymorphism genotyping arrays. Cancer Res. 2005, 65(14):6071-6079.
49. Allen R.C., Zoghbi H.Y., Moseley A.B., Rosenblatt H.M., Belmont J.W. 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. 1992, 51(6):1229-1239.
50. Amos-Landgraf J.M., Cottle A., Plenge R.M., Friez M., Schwartz C.E., Longshore J., Willard H.F. X chromosome-inactivation patterns of 1,005 phenotypically unaffected females. Am. J. Hum. Genet. 2006, 79(3):493-499.
51. Tarpey P., Parnau J., Blow M., Woffendin H., Bignell G., Cox C., Cox J., Davies H., Edkins S., Holden S., Korny A., Mallya U., et al. Mutations in the DLG3 gene cause nonsyndromic X-linked mental retardation. Am. J. Hum. Genet. 2004, 75(2):318-324.
52. Zanni G., van Esch H., Bensalem A., Saillour Y., Poirier K., Castelnau L., Ropers H.H., de Brouwer A.P., Laumonnier F., Fryns J.P., Chelly J. A novel mutation in the DLG3 gene encoding the synapse-associated protein 102 (SAP102) causes non-syndromic mental retardation. Neurogenetics 2010, 11(2):251-255.
53. Boycott K.M., Parslow M.I., Ross J.L., Miller I.P., Bech-Hansen N.T., MacLeod P.M. A familial contiguous gene deletion syndrome at Xp22.3 characterized by severe learning disabilities and ADHD. Am. J. Med. Genet. 2003, 122A(2):139-147.
54. Zinn A.R., Roeltgen D., Stefanatos G., Ramos P., Elder F.F., Kushner H., Kowal K., Ross J.L. A Turner syndrome neurocognitive phenotype maps to Xp22.3. Behav. Brain Funct. 2007, 3:24.
55. Wandstrat A.E., Conroy J.M., Zurcher V.L., Pasztor L.M., Clark B.A., Zackowski J.L., Schwartz S. Molecular and cytogenetic analysis of familial Xp deletions. Am. J. Med. Genet. 2000, 94(2):163-169.
56. Ishikawa-Brush Y., Powell J.F., Bolton P., Miller A.P., Francis F., Willard H.F., Lehrach H., Monaco A.P. Autism and multiple exostoses associated with an X;8 translocation occurring within the GRPR gene and 3' to the SDC2 gene. Hum. Mol. Genet. 1997, 6(8):1241-1250.
57. Lorenz-Depiereux B., Guido V.E., Johnson K.R., Zheng Q.Y., Gagnon L.H., Bauschatz J.D., Davisson M.T., Washburn L.L., Donahue L.R., Strom T.M., Eicher E.M. New intragenic deletions in the Phex gene clarify X-linked hypophosphatemia-related abnormalities in mice. Mamm. Genome 2004, 15(3):151-161.
58. Abidi F.E., Holinski-Feder E., Rittinger O., Kooy F., Lubs H.A., Stevenson R.E., Schwartz C.E. A novel 2 bp deletion in the TM4SF2 gene is associated with MRX58. J. Med. Genet. 2002, 39(6):430-433.
59. De Vos B., Frints S., Borghgraef M., Fryns J.P. Cognitive and behavioral characteristics in 4 affected males of a family with non-specific X-linked mental retardation and TM4 SF2-gene mutation. Genet. Couns. 2002, 13(2):191-194.
60. Maranduba C.M., Sá Moreira E., Müller Orabona G., Pavanello R.C., Vianna-Morgante A.M., Passos-Bueno M.R. Does the P172H mutation at the TM4SF2 gene cause X-linked mental retardation?. Am. J. Med. Genet. 2004, 124A(4):413-415.
61. Noor A., Gianakopoulos P.J., Fernandez B., Marshall C.R., Szatmari P., Roberts W., Scherer S.W., Vincent J.B. Copy number variation analysis and sequencing of the X-linked mental retardation gene TSPAN7/TM4SF2 in patients with autism spectrum disorder. Psychiatr. Genet. 2009, 19(3):154-155.
62. Zemni R., Bienvenu T., Vinet M.C., Sefiani A., Carrié A., Billuart P., McDonell N., Couvert P., Francis F., Chafey P., Fauchereau F., Friocourt G., et al. A new gene involved in X-linked mental retardation identified by analysis of an X; 2 balanced translocation. Nat. Genet. 2000, 24(2):167-170.
63. Cai G., Edelmann L., Goldsmith J.E., Cohen N., Nakamine A., Reichert J.G., Hoffman E.J., Zurawiecki D.M., Silverman J.M., Hollander E., Soorya L., Anagnostou E., et al. Multiplex ligation-dependent probe amplification for genetic screening in autism spectrum disorders: efficient identification of known microduplications and identification of a novel microduplication in ASMT. BMC Med. Genomics 2008, 1:50.
64. Van Esch H., Hollanders K., Badisco L., Melotte C., Van Hummelen P., Vermeesch J.R., Devriendt K., Fryns J.P., Marynen P., Froyen G. Deletion of VCX-A due to NAHR plays a major role in the occurrence of mental retardation in patients with X-linked ichthyosis. Hum. Mol. Genet. 2005, 14(13):1795-1803.
65. Cuevas-Covarrubias S.A., González-Huerta L.M. Analysis of the VCX3A, VCX2 and VCX3B genes shows that VCX3A gene deletion is not sufficient to result in mental retardation in X-linked ichthyosis. Br. J. Dermatol. 2008, 158(3):483-486.
66. Li F., Shen Y., Köhler U., Sharkey F.H., Menon D., Coulleaux L., Malan V., Rio M., Mc Mullan D.J., Cox H., Fagan K.A., Gaunt L., et al. Interstitial microduplication of Xp22.31: causative of intellectual disability or benign copy number variant?. Eur. J. Hum. Genet. 2010, 53(2):93-99.
67. Jamain S., Quach H., Betancur C., Råstam M., Colineaux C., Gillberg I.C., Soderstrom H., Giros B., Leboyer M., Gillberg C., Bourgeron T. Paris Autism Research International Sibpair Study. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat. Genet. 2003, 34(1):27-29.
68. Laumonnier F., Bonnet-Brilhault F., Gomot M., Blanc R., David A., Moizard M.P., Raynaud M., Ronce N., Lemonnier E., Calvas P., Laudier B., Chelly J., et al. X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family. Am. J. Hum. Genet. 2004, 74(3):552-557.
69. Lawson-Yuen A., Saldivar J.S., Sommer S., Picker J. Familial deletion within NLGN4 associated with autism and Tourette syndrome. Eur. J. Hum. Genet. 2008, 16(5):614-618.
70. Macarov M., Zeigler M., Newman J.P., Strich D., Sury V., Tennenbaum A., Meiner V. Deletions of VCX-A and NLGN4: a variable phenotype including normal intellect. J. Intellect. Disabil. Res. 2007, 51(Pt 5):329-333.
71. Daoud H., Bonnet-Brilhault F., Védrine S., Demattéi M.V., Vourc'h P., Bayou N., Andres C.R., Barthélémy C., Laumonnier F., Briault S. Autism and nonsyndromic mental retardation associated with a de novo mutation in the NLGN4X gene promoter causing an increased expression level. Biol. Psychiatry 2009, 66(10):906-910.
72. van Steensel M.A., Vreeburg M., Engelen J., Ghesquiere S., Stegmann A.P., Herbergs J., van Lent J., Smeets B., Vles J.H. Contiguous gene syndrome due to a maternally inherited 8.41 Mb distal deletion of chromosome band Xp22.3 in a boy with short stature, ichthyosis, epilepsy, mental retardation, cerebral cortical heterotopias and Dandy-Walker malformation. Am. J. Med. Genet. A 2008, 146A(22):2944-2949.
73. Tuffery-Giraud S., Béroud C., Leturcq F., Yaou R.B., Hamroun D., Michel-Calemard L., Moizard M.P., Bernard R., Cossée M., Boisseau P., Blayau M., Creveaux I., et al. Genotype-phenotype analysis in 2,405 patients with a dystrophinopathy using the UMD-DMD database: a model of nationwide knowledgebase. Hum. Mutat. 2009, 30(6):934-945.
74. de Leeuw N., Bulk S., Green A., Jaeckle-Santos L., Baker L.A., Zinn A.R., Kleefstra T., van der Smagt J.J., Vianne Morgante A.M., de Vries B.B., van Bokhoven H., de Brouwer A.P. UBE2A deficiency syndrome: mild to severe intellectual disability accompanied by seizures, absent speech, urogenital, and skin anomalies in male patients. Am. J. Med. Genet. A 2010, 152A(12):3084-3090.
75. Honda S., Orii K.O., Kobayashi J., Hayashi S., Imamura A., Imoto I., Nakagawa E., Goto Y., Inazawa J.A. Novel deletion at Xq24 including the UBE2A gene in a patient with X-linked mental retardation. J. Hum. Genet. 2010, 55(4):244-247.
76. Nascimento R.M.P., Otto P.A., de Brouwer A.P.M., Vianna-Morgante A.M. UBE2A, which encodes a ubiquitin-conjugating enzyme, is mutated in a novel X-linked mental retardation syndrome. Am. J. Hum. Genet. 2006, 79(3):549-555.
77. Scheffer I.E., Turner S.J., Dibbens L.M., Bayly M.A., Friend K., Hodgson B., Burrows L., Shaw M., Wei C., Ullmann R., Ropers H.H., Szepetowski P., et al. Epilepsy and mental retardation limited to females: an under-recognized disorder. Brain 2008, 131(Pt4):918-927.
78. Lugtenberg D., de Brouwer A.P., Oudakker A.R., Pfundt R., Hamel B.C., van Bokhoven H., Bongers E.M. Xq13.2q21.1 duplication encompassing the ATRX gene in a man with mental retardation, minor facial and genital anomalies, short stature and broad thorax. Am. J. Med. Genet. A 2009, 149A(4):760-766.
79. Melichar V.O., Guth S., Hellebrand H., Meindl A., von der Hardt K., Kraus C., Trautmann U., Rascher W., Rauch A. A male infant with a 9.6 Mb terminal Xp deletion including the OA1 locus: limit of viability of Xp deletions in males. Am. J. Med. Genet. A 2007, 143(2):135-141.