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Neuropediatrics 2016; 47(01): 051-056
DOI: 10.1055/s-0035-1566233
Short Communication
Georg Thieme Verlag KG Stuttgart · New York

Xp11.22 Microduplications Including HUWE1: Case Report and Literature Review

Sonia Orivoli
1   Child Neuropsychiatry Unit, Department of Neuroscience, University-Hospital of Parma, Parma, Italy
,
Elena Pavlidis
1   Child Neuropsychiatry Unit, Department of Neuroscience, University-Hospital of Parma, Parma, Italy
,
Gaetano Cantalupo
2   Child Neuropsychiatry Unit, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy
,
Marianna Pezzella
3   Muscular and Neurodegenerative Disease Unit, Institute G. Gaslini, Genova, Italy
,
Federico Zara
3   Muscular and Neurodegenerative Disease Unit, Institute G. Gaslini, Genova, Italy
,
Livia Garavelli
4   Clinical Genetics Unit, IRCCS, S. Maria Nuova Hospital, Reggio Emilia, Italy
,
Francesco Pisani
1   Child Neuropsychiatry Unit, Department of Neuroscience, University-Hospital of Parma, Parma, Italy
,
Benedetta Piccolo
5   Child Neuropsychiatry Unit, Mother and Child Department, University-Hospital of Parma, Parma, Italy
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Publikationsverlauf

19. Juni 2015

12. September 2015

Publikationsdatum:
20. November 2015 (online)

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Abstract

Xp11.22 microduplications have been reported in different patients with X-linked intellectual disability. Comparing the duplicated segments, a minimum region of overlap has been identified. Within this region, only one gene, the HUWE1 gene, coding the E3 ubiquitin protein ligase, turned out to be duplicated in all previously described patients. We provide a review of the literature on this topic, making a comparison not only of genetic aspects, but also of clinical, neurophysiological, and neuroradiological findings. Furthermore, we describe the phenotypic and molecular characterization of a case of intellectual disability in a child carrying one of the smallest Xp11.22 microduplications reported, involving the whole sequence of HUWE1 gene. Unlike previously described cases, our patient's neuroimaging showed abnormal findings; he also experienced one seizure and showed interictal electroencephalogram (EEG) epileptiform abnormalities. Given the fact that HUWE1 duplications and mutations have previously been described in several patients with X-linked cognitive impairment, our findings support the hypothesis that HUWE1 gene might be implicate in the pathogenesis of intellectual disability. Nevertheless, further investigations and a more detailed examination of patients' clinical history are needed to clear up other eventual genotype–phenotype correlations, such as the presence of epilepsy/epileptiform EEG abnormalities.

Keywords

intellectual disability - HUWE1 - X-linked - EEG abnormalities
 

  • References

  • 1 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
    CrossrefPubMedSuche in Google Scholar
  • 2 Mercier C, Saxena S, Lecomte J, Cumbrera MG, Harnois G. WHO Atlas on Global Resources for Persons with Intellectual Disabilities 2007: Key Findings Relevant for Low- and Middle-Income Countries. Journal of Policy and Practice in Intellectual Disabilities 2008; 5 (2) 81-88
    CrossrefPubMedSuche in Google Scholar
  • 3 Roeleveld N, Zielhuis GA, Gabreëls F. The prevalence of mental retardation: a critical review of recent literature. Dev Med Child Neurol 1997; 39 (2) 125-132
    PubMedSuche in Google Scholar
  • 4 Frints SG, Froyen G, Marynen P, Fryns JP. X-linked mental retardation: vanishing boundaries between non-specific (MRX) and syndromic (MRXS) forms. Clin Genet 2002; 62 (6) 423-432
    CrossrefPubMedSuche in Google Scholar
  • 5 Lubs HA, Stevenson RE, Schwartz CE. Fragile X and X-linked intellectual disability: four decades of discovery. Am J Hum Genet 2012; 90 (4) 579-590
    CrossrefPubMedSuche in Google Scholar
  • 6 Froyen G, Corbett M, Vandewalle J , et al. Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation. Am J Hum Genet 2008; 82 (2) 432-443
    CrossrefPubMedSuche in Google Scholar
  • 7 Froyen G, Belet S, Martinez F , et al. Copy-number gains of HUWE1 due to replication- and recombination-based rearrangements. Am J Hum Genet 2012; 91 (2) 252-264
    CrossrefPubMedSuche in Google Scholar
  • 8 Narahara K, Kodama Y, Kimura S, Kimoto H. Probable inverted tandem duplication of Xp in a 46,Xp+Y boy. Jinrui Idengaku Zasshi 1979; 24 (2) 105-110
    CrossrefPubMedSuche in Google Scholar
  • 9 Bernstein R, Pinto MR, Almeida M, Solarsh SM, Meck J, Jenkins T. X;Y translocation in an adolescent mentally normal phenotypic male with features of hypogonadism. J Med Genet 1980; 17 (6) 437-443
    CrossrefPubMedSuche in Google Scholar
  • 10 Wyandt HE, Bugeau-Michaud L, Skare JC, Milunsky A. Partial duplication of Xp: a case report and review of previously reported cases. Am J Med Genet 1991; 40 (3) 280-283
    CrossrefPubMedSuche in Google Scholar
  • 11 Telvi L, Ion A, Carel JC , et al. A duplication of distal Xp associated with hypogonadotrophic hypogonadism, hypoplastic external genitalia, mental retardation, and multiple congenital abnormalities. J Med Genet 1996; 33 (9) 767-771
    CrossrefPubMedSuche in Google Scholar
  • 12 Zhang A, Weaver DD, Palmer CG. Molecular cytogenetic identification of four X chromosome duplications. Am J Med Genet 1997; 68 (1) 29-38
    CrossrefPubMedSuche in Google Scholar
  • 13 Ogata T, Kosho T, Wakui K, Fukushima Y, Yoshimoto M, Miharu N. Short stature homeobox-containing gene duplication on the der(X) chromosome in a female with 45,X/46,X, der(X), gonadal dysgenesis, and tall stature. J Clin Endocrinol Metab 2000; 85 (8) 2927-2930
    CrossrefPubMedSuche in Google Scholar
  • 14 Kokalj Vokac N, Seme Ciglenecki P, Erjavec A, Zagradisnik B, Zagorac A. Partial Xp duplication in a girl with dysmorphic features: the change in replication pattern of late-replicating dupX chromosome. Clin Genet 2002; 61 (1) 54-61
    CrossrefPubMedSuche in Google Scholar
  • 15 Dupont C, Lebbar A, Teinturier C , et al. First reported case of intrachromosomal cryptic inv dup del Xp in a boy with developmental retardation. Am J Med Genet A 2007; 143A (11) 1236-1243
    CrossrefPubMedSuche in Google Scholar
  • 16 Tachdjian G, Aboura A, Portnoï MF , et al. Cryptic Xp duplication including the SHOX gene in a woman with 46,X, del(X)(q21.31) and premature ovarian failure. Hum Reprod 2008; 23 (1) 222-226
    CrossrefPubMedSuche in Google Scholar
  • 17 Tzschach A, Chen W, Erdogan F , et al. Characterization of interstitial Xp duplications in two families by tiling path array CGH. Am J Med Genet A 2008; 146A (2) 197-203
    CrossrefPubMedSuche in Google Scholar
  • 18 del Rey G, Jasper H, Bengolea SV, Boywitt A, De Bellis R, Heinrich JJ. Trisomy of the short stature homeobox-containing gene (SHOX) due to duplication/deletion of the X chomosome: clinical implications on the stature. Horm Res Paediatr 2010; 74 (4) 297-304
    CrossrefPubMedSuche in Google Scholar
  • 19 Piccione M, Sanfilippo C, Cavani S , et al. Molecular and clinical characterization of a small duplication Xp in a human female with psychiatric disorders. J Genet 2011; 90 (3) 473-477
    CrossrefPubMedSuche in Google Scholar
  • 20 Gedeon A, Kerr B, Mulley J, Turner G. Pericentromeric genes for non-specific X-linked mental retardation (MRX). Am J Med Genet 1994; 51 (4) 553-564
    CrossrefPubMedSuche in Google Scholar
  • 21 Donnelly AJ, Partington MW, Ryan AK, Mulley JC. Regional localisation of two non-specific X-linked mental retardation genes (MRX30 and MRX31). Am J Med Genet 1996; 64 (1) 113-120
    CrossrefPubMedSuche in Google Scholar
  • 22 Madrigal I, Rodríguez-Revenga L, Armengol L , 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
    CrossrefPubMedSuche in Google Scholar
  • 23 Santos-Rebouças CB, de Almeida LG, Belet S , et al. Novel microduplications at Xp11.22 including HUWE1: clinical and molecular insights into these genomic rearrangements associated with intellectual disability. J Hum Genet 2015; 60 (4) 207-211
    CrossrefPubMedSuche in Google Scholar
  • 24 Adamson KA, Cross I, Batch JA, Rappold GA, Glass IA, Ball SG. Trisomy of the short stature homeobox-containing gene (SHOX), resulting from a duplication-deletion of the X chromosome. Clin Endocrinol (Oxf) 2002; 56 (5) 671-675
    CrossrefPubMedSuche in Google Scholar
  • 25 Bonnet C, Grégoire MJ, Brochet K, Raffo E, Leheup B, Jonveaux P. Pure de-novo 5 Mb duplication at Xp11.22-p11.23 in a male: phenotypic and molecular characterization. J Hum Genet 2006; 51 (9) 815-821
    CrossrefPubMedSuche in Google Scholar
  • 26 Edens AC, Lyons MJ, Duron RM, Dupont BR, Holden KR. Autism in two females with duplications involving Xp11.22-p11.23. Dev Med Child Neurol 2011; 53 (5) 463-466
    CrossrefPubMedSuche in Google Scholar
  • 27 Holden ST, Clarkson A, Thomas NS, Abbott K, James MR, Willatt L. A de novo duplication of Xp11.22-p11.4 in a girl with intellectual disability, structural brain anomalies, and preferential inactivation of the normal X chromosome. Am J Med Genet A 2010; 152A (7) 1735-1740
    CrossrefPubMedSuche in Google Scholar
  • 28 Kolomietz E, Godbole K, Winsor EJ, Stockley T, Seaward G, Chitayat D. Functional disomy of Xp: prenatal findings and postnatal outcome. Am J Med Genet A 2005; 134 (4) 393-398
    PubMedSuche in Google Scholar
  • 29 Matsuo M, Muroya K, Kosaki K , et al. Random X-inactivation in a girl with duplication Xp11.21-p21.3: report of a patient and review of the literature. Am J Med Genet 1999; 86 (1) 44-50
    CrossrefPubMedSuche in Google Scholar
  • 30 Nielsen KB, Langkjaer F. Inherited partial X chromosome duplication in a mentally retarded male. J Med Genet 1982; 19 (3) 222-224
    CrossrefPubMedSuche in Google Scholar
  • 31 Portnoï MF, Bouayed-Abdelmoula N, Mirc M , et al. Molecular cytogenetic analysis of a duplication Xp in a female with an abnormal phenotype and random X inactivation. Clin Genet 2000; 58 (2) 116-122
    PubMedSuche in Google Scholar
  • 32 Shchelochkov OA, Cooper ML, Ou Z , et al. Mosaicism for r(X) and der(X)del(X)(p11.23)dup(X)(p11.21p11.22) provides insight into the possible mechanism of rearrangement. Mol Cytogenet 2008; 1: 16-25
    CrossrefPubMedSuche in Google Scholar
  • 33 Vandewalle J, Langen M, Zschätzsch M , et al. Ubiquitin ligase HUWE1 regulates axon branching through the Wnt/β-catenin pathway in a Drosophila model for intellectual disability. PLoS ONE 2013; 8 (11) e81791
    CrossrefPubMedSuche in Google Scholar
  • 34 Isrie M, Kalscheuer VM, Holvoet M, Fieremans N, Van Esch H, Devriendt K. HUWE1 mutation explains phenotypic severity in a case of familial idiopathic intellectual disability. Eur J Med Genet 2013; 56 (7) 379-382
    CrossrefPubMedSuche in Google Scholar
  • 35 D'Arca D, Zhao X, Xu W, Ramirez-Martinez NC, Iavarone A, Lasorella A. Huwe1 ubiquitin ligase is essential to synchronize neuronal and glial differentiation in the developing cerebellum. Proc Natl Acad Sci U S A 2010; 107 (13) 5875-5880
    CrossrefPubMedSuche in Google Scholar
  • 36 Mefford HC, Sharp AJ, Baker C , et al. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N Engl J Med 2008; 359 (16) 1685-1699
    CrossrefPubMedSuche in Google Scholar