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Novel association of severe neonatal encephalopathy and Hirschsprung disease in a male with a duplication at the Xq28 region.

ABSTRACT: BACKGROUND: Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of parasympathetic intrinsic ganglion cells in the submucosal and myenteric plexuses along a variable portion of the intestinal tract. In approximately 18% of the cases HSCR also presents with multiple congenital anomalies including recognized syndromes. METHODS: A combination of MLPA and microarray data analysis have been undertaken to refine a duplication at the Xq28 region. RESULTS: In this study we present a new clinical association of severe neonatal encephalopathy (Lubs syndrome) and HSCR, in a male patient carrying a duplication at the Xq28 region which encompasses the MECP2 and L1CAM genes. CONCLUSIONS: While the encephalopathy has been traditionally attributed to the MECP2 gene duplication in patients with Lubs syndrome, here we propose that the enteric phenotype in our patient might be due to the dosage variation of the L1CAM protein, together with additional molecular events not identified yet. This would be in agreement with the hypothesis previously forwarded that mutations in L1CAM may be involved in HSCR development in association with a predisposing genetic background.

SUBMITTER: Fernandez RM

PROVIDER: S-EPMC2955569 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Novel association of severe neonatal encephalopathy and Hirschsprung disease in a male with a duplication at the Xq28 region.

Fernández Raquel M RM Núñez-Torres Rocío R González-Meneses Antonio A Antiñolo Guillermo G Borrego Salud S

BMC medical genetics 20100922

<h4>Background</h4>Hirschsprung disease (HSCR) is a neurocristopathy characterized by the absence of parasympathetic intrinsic ganglion cells in the submucosal and myenteric plexuses along a variable portion of the intestinal tract. In approximately 18% of the cases HSCR also presents with multiple congenital anomalies including recognized syndromes.<h4>Methods</h4>A combination of MLPA and microarray data analysis have been undertaken to refine a duplication at the Xq28 region.<h4>Results</h4>I ...[more]

PMID: 20860806

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Project description:BackgroundTourette syndrome (TS) is a complex neurodevelopmental disorder (NDD) characterized by multiple chronic involuntary motor and vocal tics with onset during childhood or adolescence. Most TS patients present with additional comorbidities, typically attention deficit hyperactivity disorder (ADHD), obsessive- compulsive disorder (OCD), autism spectrum disorder (ASD) and intellectual disability (ID). Both TS and ID are genetically complex disorders that likely occur as a result of the effects of multiple genes interacting with other environmental factors. In addition to single gene mutations and chromosomal disorders, copy number variations (CNVs) are implicated across many NDDs and ID and contribute to their shared genetic etiology. Screening of CNVs using microarray-based Comparative Genomic Hybridization (aCGH) is now routinely performed in all subjects with NDD and ID.Case presentationWe report a case of a 12-year-old girl diagnosed with Gilles de la Tourette Syndrome associated to behavior disorders and intellectual disability in particular with regard to language. Array-CGH analysis showed a CNV of a subtelomeric region Xq28 (gain of 260 kb) inherited from the healthy father. The duplication contains two genes, VAMP7 and SPRY3 of the PAR2 pseudoautosomal region. FISH analysis revealed that the duplicated segment is located on the short arm of a chromosome 13, resulting in a trisomy of the region. In the proband the expression levels of the genes evaluated in the peripheral blood sample are comparable both those of the mother and to those of female control subjects.ConclusionsAlthough the trisomy of the 260 kb region from Xq28 identified in proband is also shared by the healthy father, it is tantalizing to speculate that, together with genetic risk factors inherited from the mother, it may play a role in the development of a form of Tourette syndrome with intellectual disability. This hypothesis is also supported by the fact that both genes present in the duplicated region (VAMP7 and SPRY3) are expressed in the CNS and are implicated in neurotransmission and neurite growth and branching. In addition, similar CNVs have been identified in individuals whose phenotype is associated with autism spectrum disorders or intellectual disability.

Dataset Information

Novel association of severe neonatal encephalopathy and Hirschsprung disease in a male with a duplication at the Xq28 region.

Publications

Novel association of severe neonatal encephalopathy and Hirschsprung disease in a male with a duplication at the Xq28 region.

Similar Datasets

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