2010
DOI: 10.1007/s00439-009-0778-7
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Clinical characterization of individuals with deletions of genes in holoprosencephaly pathways by aCGH refines the phenotypic spectrum of HPE

Abstract: Holoprosencephaly (HPE) is the most common developmental forebrain anomaly in humans. Both environmental and genetic factors have been identified to play a role in the HPE phenotype. Previous studies of the genetic bases of HPE have taken a phenotype-first approach by examining groups of patients with HPE for specific mutations or deletions in known or candidate HPE genes. In this study, we characterized the presence or absence of HPE or a microform in 136 individuals in which microarray-based comparative geno… Show more

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Cited by 70 publications
(67 citation statements)
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“…16 Our patient suggests that a role for SIX2 in craniofacial dysmorphism is, at best, subject to reduced penetrance. Similarly, lack of holoprosencephaly on brain magnetic resonance imaging in our patient despite haploinsufficiency for SIX3, one of the four major holoprosencephaly genes, 17 suggests that this may be an example of incomplete penetrance of the holoprosencephaly phenotype in association with SIX3 deletion.…”
Section: Discussionsupporting
confidence: 57%
“…16 Our patient suggests that a role for SIX2 in craniofacial dysmorphism is, at best, subject to reduced penetrance. Similarly, lack of holoprosencephaly on brain magnetic resonance imaging in our patient despite haploinsufficiency for SIX3, one of the four major holoprosencephaly genes, 17 suggests that this may be an example of incomplete penetrance of the holoprosencephaly phenotype in association with SIX3 deletion.…”
Section: Discussionsupporting
confidence: 57%
“…To the best of our knowledge, the occurrence of both anomalies has been reported in only three [McCormack et al, 2003;Alanay et al, 2005]. In addition, Rosenfeld et al [2010] reported a patient with a microform of holoprosencephaly and a DandyWalker malformation variant who had a terminal 7q deletion. The pathogenesis of holoprosencephaly is complex and multigenetic [Gekas et al, 2012].…”
Section: Discussionmentioning
confidence: 93%
“…This suggests that, in addition to alterations in TGIF , other genetic modifiers (on 18p or other chromosomal regions) or environmental factors are necessary to result in HPE. TSWG1 , as described above, was initially hypothesized to be one such genetic modifier, as it has been linked to forebrain development, although recent mutation analysis of the coding region of TWSG1 suggests that this gene does not play a significant role in human HPE [Petryk et al, 2004;Rosenfeld et al, 2010;Kauvar et al, 2011]. Another possibility may relate to the fact that mice with Tgif mutations have increased susceptibility to the teratogen retinoic acid [Bartholin et al, 2006].…”
Section: Discussionmentioning
confidence: 99%
“…Referenced patients were included in this analysis if there was a confirmed mutation affecting TGIF . Also included in the analysis were patients with clinical features of HPE and cytogenetic anomalies affecting the short arm of chromosome 18 (18p) without additional chromosomal abnormalities and with clear evidence that the deletion includes the TGIF locus at 18p11.3 [Münke et al, 1988;Münke, 1989;Roessler and Muenke, 1998;Aguilella et al, 2003;Bendavid et al, 2006Bendavid et al, , 2009El-Jaick et al, 2007;Richieri-Costa and Ribeiro, 2008;Sepulveda, 2009;Rosenfeld et al, 2010]. Cases involving deletions of 18p were only included in the final statistical analysis of phenotypes if clinical findings were consistent with HPE-spectrum anomalies.…”
Section: Methodsmentioning
confidence: 99%