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

作者：Czeschik Johanna Christina; Bauer Peter; Buiting Karin; Dufke Claudia; Guillen Navarro Encarna; Johnson Diana S; Koehler Udo; Lopez Gonzalez Vanesa; Luedecke Hermann Josef; Male Alison; Morrogh Deborah; Riess Angelika; Tzschach Andreas; Wieczorek Dagmar; Kuechler Alma^*

来源：Orphanet Journal of Rare Diseases, 2013, 8(1): UNSP 146.

DOI：10.1186/1750-1172-8-146

• UBE2A
• RAD6A
• HHR6A
• Ubiquitin-conjugating enzyme
• Intellectual disability
• Synophrys
• Prominent supraorbital ridges
• Onychodystrophy

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. %26lt;br%26gt;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.

• 出版日期2013-9-21
• 单位河北医科大学