X-linked intellectual disability type Nascimento is a clinically distinct, probably underdiagnosed entity

Orphanet Journal of Rare Diseases

Alma Kuechler⁴  Dagmar Wieczorek⁴  Andreas Tzschach³  Angelika Rieß³  Deborah Morrogh²  Alison Male²  Hermann-Josef Lüdecke⁴  Vanesa López-González¹  Udo Koehler⁵  Diana S Johnson⁶  Encarna Guillén-Navarro¹  Claudia Dufke³  Karin Buiting⁴  Peter Bauer³  Johanna Christina Czeschik⁴ 

[1] Unidad de Genética Médica, Servicio de Pediatría, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain;Great Ormond Street Hospital for Children, London, UK;Institut für Medizinische Genetik und Angewandte Genomik, Universitätsklinikum Tübingen, Tübingen, Germany;Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Hufelandstr. 55, 45122, Essen, Germany;MGZ - Medizinisch Genetisches Zentrum, München, Germany;Sheffield Children’s Hospital, Sheffield, UK

关键词: Onychodystrophy;    Prominent supraorbital ridges;    Synophrys;    Intellectual disability;    Ubiquitin-conjugating enzyme;    HHR6A;    RAD6A;    UBE2A;   

Others  :  863528
DOI  :  10.1186/1750-1172-8-146

 received in 2013-07-09, accepted in 2013-09-15,  发布年份 2013

【 摘 要 】

X-linked intellectual disability type Nascimento (MIM #300860), caused by mutations in UBE2A (MIM *312180), is characterized by craniofacial dysmorphism (synophrys, prominent supraorbital ridges, deep-set, almond-shaped eyes, depressed nasal bridge, prominent columella, hypoplastic alae nasi, and macrostomia), skin anomalies (hirsutism, myxedematous appearance, onychodystrophy), micropenis, moderate to severe intellectual disability (ID), motor delay, impaired/absent speech, and seizures. Hitherto only five familial point mutations and four different deletions including UBE2A have been reported in the literature.

We present eight additional individuals from five families with UBE2A associated ID - three males from a consanguineous family, in whom we identified a small deletion of only 7.1 kb encompassing the first three exons of UBE2A, two related males with a UBE2A missense mutation in exon 4, a patient with a de novo nonsense mutation in exon 6, and two sporadic males with larger deletions including UBE2A. All affected male individuals share the typical clinical phenotype, all carrier females are unaffected and presented with a completely skewed X inactivation in blood. We conclude that 1.) X-linked intellectual disability type Nascimento is a clinically very distinct entity that might be underdiagnosed to date. 2.) So far, all females carrying a familial UBE2A aberration have a completely skewed X inactivation and are clinically unaffected. This should be taken in to account when counselling those families. 3.) The coverage of an array should be checked carefully prior to analysis since not all arrays have a sufficient resolution at specific loci, or alternative quantitative methods should be applied not to miss small deletions.

【 授权许可】

   
2013 Czeschik et al.; licensee BioMed Central Ltd.

【 图 表 】

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