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Hypertelorism

About: Hypertelorism is a research topic. Over the lifetime, 2054 publications have been published within this topic receiving 38928 citations. The topic is also known as: Hypertelorism of Orbit.


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Journal ArticleDOI
TL;DR: An additional cohort of 40 patients who had vascular Ehlers–Danlos syndrome without the characteristic type III collagen abnormalities or the craniofacial features of the Loeys–Dietz syndrome were screened and a mutation in TGFBR1 or TGF BR2 was found.
Abstract: Background The Loeys–Dietz syndrome is a recently described autosomal dominant aortic-aneurysm syndrome with widespread systemic involvement The disease is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate and is caused by heterozygous mutations in the genes encoding transforming growth factor β receptors 1 and 2 (TGFBR1 and TGFBR2, respectively) Methods We undertook the clinical and molecular characterization of 52 affected families Forty probands presented with typical manifestations of the Loeys–Dietz syndrome In view of the phenotypic overlap between this syndrome and vascular Ehlers–Danlos syndrome, we screened an additional cohort of 40 patients who had vascular Ehlers–Danlos syndrome without the characteristic type III collagen abnormalities or the craniofacial features of the Loeys–Dietz syndrome Results We found a mutation in TGFBR1 or TGFBR2 in all probands with typical Loeys–Dietz syndrome (type I) and in 12 probands presenting

1,391 citations

Journal ArticleDOI
11 Nov 1999-Nature
TL;DR: It is shown that five unrelated ICF patients have mutations in both alleles of the gene that encodes DNA methyltransferase 3B (refs 5, 6), which is the only genetic disorder known to involve constitutive abnormalities of genomic methylation patterns.
Abstract: The recessive autosomal disorder known as ICF syndrome (for immunodeficiency, centromere instability and facial anomalies; Mendelian Inheritance in Man number 242860) is characterized by variable reductions in serum immunoglobulin levels which cause most ICF patients to succumb to infectious diseases before adulthood. Mild facial anomalies include hypertelorism, low-set ears, epicanthal folds and macroglossia. The cytogenetic abnormalities in lymphocytes are exuberant: juxtacentromeric heterochromatin is greatly elongated and thread-like in metaphase chromosomes, which is associated with the formation of complex multiradiate chromosomes. The same juxtacentromeric regions are subject to persistent interphase self-associations and are extruded into nuclear blebs or micronuclei. Abnormalities are largely confined to tracts of classical satellites 2 and 3 at juxtacentromeric regions of chromosomes 1, 9 and 16. Classical satellite DNA is normally heavily methylated at cytosine residues, but in ICF syndrome it is almost completely unmethylated in all tissues. ICF syndrome is the only genetic disorder known to involve constitutive abnormalities of genomic methylation patterns. Here we show that five unrelated ICF patients have mutations in both alleles of the gene that encodes DNA methyltransferase 3B (refs 5, 6). Cytosine methylation is essential for the organization and stabilization of a specific type of heterochromatin, and this methylation appears to be carried out by an enzyme specialized for the purpose.

1,144 citations

Journal ArticleDOI
10 Jun 2010-Nature
TL;DR: In vitro-derived cardiomyocytes from LEOPARD syndrome iPSCs are larger, have a higher degree of sarcomeric organization and preferential localization of NFATC4 in the nucleus when compared with cardiomeocytes derived from human embryonic stem cells or wild-type iPSC derived from a healthy brother of one of the LEopARD syndrome patients, which correlate with a potential hypertrophic state.
Abstract: The generation of reprogrammed induced pluripotent stem cells (iPSCs) from patients with defined genetic disorders holds the promise of increased understanding of the aetiologies of complex diseases and may also facilitate the development of novel therapeutic interventions. We have generated iPSCs from patients with LEOPARD syndrome (an acronym formed from its main features; that is, lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary valve stenosis, abnormal genitalia, retardation of growth and deafness), an autosomal-dominant developmental disorder belonging to a relatively prevalent class of inherited RAS-mitogen-activated protein kinase signalling diseases, which also includes Noonan syndrome, with pleomorphic effects on several tissues and organ systems. The patient-derived cells have a mutation in the PTPN11 gene, which encodes the SHP2 phosphatase. The iPSCs have been extensively characterized and produce multiple differentiated cell lineages. A major disease phenotype in patients with LEOPARD syndrome is hypertrophic cardiomyopathy. We show that in vitro-derived cardiomyocytes from LEOPARD syndrome iPSCs are larger, have a higher degree of sarcomeric organization and preferential localization of NFATC4 in the nucleus when compared with cardiomyocytes derived from human embryonic stem cells or wild-type iPSCs derived from a healthy brother of one of the LEOPARD syndrome patients. These features correlate with a potential hypertrophic state. We also provide molecular insights into signalling pathways that may promote the disease phenotype.

695 citations

Journal ArticleDOI
TL;DR: Nine patients with remarkably similar facies with a previously unrecognized syndrome of valvular pulmonary stenosis and multiple extra cardiac anomalies with similar associated lesions are reported on in 1962.
Abstract: AT THE meeting of the Mid-Western Society for Pediatric Research in 1962, I reported on nine patients with remarkably similar facies with a previously unrecognized syndrome of valvular pulmonary stenosis and multiple extra cardiac anomalies.1Review of the literature at that time showed that several males resembling these patients had been reported under several different headings, most commonly under the designation of, "the male Turner syndrome."2-5There were no definite reports of similarly affected female patients. In that report I spoke in terms of a "new syndrome" in order to stress that this condition could affect not only males but also females, and that it was also clinically and etiologically different from the true Turner6syndrome. Since that time, a further eight patients, five males and three females, with valvular pulmonary stenosis and similar associated lesions have been studied. An additional two patients, one of each sex,

515 citations

Journal ArticleDOI
TL;DR: Two PHS families with frameshift mutations in GLI3 that are 3′ of the zinc finger-encoding domains are reported, including one family with a de novo mutation, which implicate mutations inGLI3 as the cause of autosomal dominant PHS, and suggest that frameshIFT mutations of the GLi3 transcription factor gene can alter the development of multiple organ systems in vertebrates.
Abstract: Pallister-Hall syndrome (PHS, M146510) was first described in 1980 in six newborns. It is a pleiotropic disorder of human development that comprises hypothalamic hamartoma, central polydactyly, and other malformations. This disorder is inherited as an autosomal dominant trait and has been mapped to 7p13 (S. Kang et al. Autosomal dominant Pallister-Hall syndrome maps to 7p13. Am. J. Hum. Genet. 59, A81 (1996)), co-localizing the PHS locus and the GLI3 zinc finger transcription factor gene. Large deletions or translocations resulting in haploinsufficiency of the GLI3 gene have been associated with Greig cephalopolysyndactyly syndrome (GCPS; M175700) although no mutations have been identified in GCPS patients with normal karyotypes. Both PHS and GCPS have polysyndactyly, abnormal craniofacial features and are inherited in an autosomal dominant pattern, but they are clinically distinct. The polydactyly of GCPS is commonly preaxial and that of PHS is typically central or postaxial. No reported cases of GCPS have hypothalamic hamartoma and PHS does not cause hypertelorism or broadening of the nasal root or forehead. The co-localization of the loci for PHS and GCPS led us to investigate GLI3 as a candidate gene for PHS. Herein we report two PHS families with frameshift mutations in GLI3 that are 3' of the zinc finger-encoding domains, including one family with a de novo mutation. These data implicate mutations in GLI3 as the cause of autosomal dominant PHS, and suggest that frameshift mutations of the GLI3 transcription factor gene can alter the development of multiple organ systems in vertebrates.

493 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202333
202286
202159
202053
201942
201854