Cutis Aplasia as a clinical hallmark for the syndrome associated with 19q13.11 deletion: the possible role for UBA2 gene.

Joana B Melo,Jorge Saraiva,Alexandra Estevinho,Lina Ramos,Isabel M Carreira

doi:10.1186/s13039-015-0123-x

Abstract

BackgroundWide genome screening through array comparative genomic hybridization made possible the recognition of the novel 19q13.11 deletion syndrome. There are very few cases reported with this deletion, but clinically this condition seems to be recognizable by pre and postnatal growth retardation, microcephaly, developmental delay/intellectual disabilities, speech disturbance, hypospadias (in males) and signs of ectodermal dysplasia and cutis aplasia over the posterior occiput.ResultsUsing oligoarray CGH, a 4.6 Mb deletion in 19q13.11q13.12 was detected in a 23 year old female patient that presented clinical features previously associated with 19q13.11 deletion.ConclusionsOur work reinforces the idea that a region encompassing four zinc finger genes is likely to be responsible for the syndrome, and that the difference in minor clinical manifestation depends on the genes present outside the minimal overlapping region proposed for this syndrome. We also review all cases described in the literature and discuss the correlation between haploinsufficiency of UBA2 gene and cutis aplasia present in the majority of the patients reported, and its importance as a clinical hallmark of 19q13.11 deletion syndrome, when associated with more common features like developmental delay, microcephaly, speech disturbance and hypospadias in males.

Highlights

Wide genome screening through array comparative genomic hybridization made possible the recognition of the novel 19q13.11 deletion syndrome
In this study we identified another patient with a de novo 19q13.11q13.12 deletion, harboring the minimal overlapping region (MOR) pointed by Gana et al as the critical region for the 19q13.11 deletion syndrome (Figure 2) [6]
The hypothesis that the haploinsuffiency of these genes could be the cause for mental retardation and speech disturbance is supported by the fact that zinc finger genes are involved in X-linked mental retardation in males, and that ZNF clusters are suspected to contribute to higher cognitive function in primates [11-14]

Summary

Introduction

Wide genome screening through array comparative genomic hybridization made possible the recognition of the novel 19q13.11 deletion syndrome. There are very few cases reported with this deletion, but clinically this condition seems to be recognizable by pre and postnatal growth retardation, microcephaly, developmental delay/intellectual disabilities, speech disturbance, hypospadias (in males) and signs of ectodermal dysplasia and cutis aplasia over the posterior occiput. The development of array comparative genomic hybridization technique (array CGH) greatly improved the detection of cryptic unbalanced rearrangements in mental retardation patients and made possible the identification of novel microdeletion and microduplication syndromes [1]. A total of 8 mental retardation patients and 1 aborted fetus, carrying the 19q13.11 deletion have been reported until now in addition to two more cases included in the Database of Chromosome Imbalance and Phenotype in Humans using Ensembl Resources (DECIPHER) [2,3,4,5,6,7]. All these patients presented common features and the deletion of 19q13.11 is proposed as a new clinical recognizable syndrome [3].

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Results

Discussion

Conclusion