Refinement of the critical 2p25.3 deletion region: the role of MYT1L in intellectual disability and obesity
Purpose: Submicroscopic deletions of chromosome band 2p25.3 are associated with intellectual disability and/or central obesity. Although MYT1L is believed to be a critical gene responsible for intellectual disability, so far no unequivocal data have confirmed this hypothesis. Methods: In this study...
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Veröffentlicht in: | Genetics in medicine 2015-06, Vol.17 (6), p.460-466 |
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Sprache: | eng |
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Zusammenfassung: | Purpose:
Submicroscopic deletions of chromosome band 2p25.3 are associated with intellectual disability and/or central obesity. Although
MYT1L
is believed to be a critical gene responsible for intellectual disability, so far no unequivocal data have confirmed this hypothesis.
Methods:
In this study we evaluated a cohort of 22 patients (15 sporadic patients and two families) with a 2p25.3 aberration to further refine the clinical phenotype and to delineate the role of
MYT1L
in intellectual disability and obesity. In addition,
myt1l
spatiotemporal expression in zebrafish embryos was analyzed by quantitative polymerase chain reaction and whole-mount in situ hybridization.
Results:
Complete
MYT1L
deletion, intragenic deletion, or duplication was observed in all sporadic patients, in addition to two patients with a de novo point mutation in
MYT1L
. The familial cases comprise a 6-Mb deletion in a father and his three children and a 5′
MYT1L
overlapping duplication in a father and his two children. Expression analysis in zebrafish embryos shows specific
myt1l
expression in the developing brain.
Conclusion:
Our data strongly strengthen the hypothesis that
MYT1L
is the causal gene for the observed syndromal intellectual disability. Moreover, because 17 patients present with obesity/overweight, haploinsufficiency of
MYT1L
might predispose to weight problems with childhood onset.
Genet Med
17
6, 460–466. |
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ISSN: | 1098-3600 1530-0366 |
DOI: | 10.1038/gim.2014.124 |