The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Françoise Meire - One of the best experts on this subject based on the ideXlab platform.
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LTBP2 null mutations in an autosomal recessive ocular syndrome with Megalocornea, spherophakia, and secondary glaucoma
European Journal of Human Genetics, 2010Co-Authors: Julie Desir, Yves Sznajer, Fanny Depasse, Françoise Roulez, Marc Schrooyen, Françoise Meire, Marc AbramowiczAbstract:The latent TGF β -binding proteins (LTBPs) and fibrillins are a superfamily of large, multidomain proteins with structural and TGF β -signalling roles in the extracellular matrix. Their importance is underscored by fibrillin-1 mutations responsible for Marfan syndrome, but their respective roles are still incompletely understood. We report here on two families where children from healthy, consanguineous parents, presented with Megalocornea and impaired vision associated with small, round, dislocated lenses (microspherophakia and ectopia lentis) and myopia, as well as a high-arched palate, and, in older children, tall stature with an abnormally large arm span over body height ratio, that is, associated features of Marfan syndrome. Glaucoma was not present at birth, but was diagnosed in older children. Whole genome homozygosity mapping followed by candidate gene analysis identified homozygous truncating mutations of LTBP2 gene in patients from both families. Fibroblast mRNA analysis was consistent with nonsense-mediated mRNA decay, with no evidence of mutated exon skipping. We conclude that biallelic null LTBP2 mutations cause the ocular phenotype in both families and could lead to Marfan-like features in older children. We suggest that intraocular pressures should be followed-up in young children with an ocular phenotype consisting of Megalocornea, spherophakia and/or lens dislocation, and recommend LTBP2 gene analysis in these patients.
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biometry in x linked Megalocornea pathognomonic findings
British Journal of Ophthalmology, 1994Co-Authors: Françoise Meire, Jw DellemanAbstract:Biometric study in a series of 11 affected males provides characteristic findings. The patients present with a large cornea with short radius, very deep anterior chamber depth (AC depth) exceeding the normal mean value of plus 2 SD, and a short vitreous length. Calculation of the postlimbal depth, a method applied in this study to obtain information about positioning of the iris and the lens, reveals a posterior positioning of the iris and lens. The posterior positioning of the iris and lens was proved to occur at the expense of the vitreous. The importance of biometric data for diagnosis and for differential diagnosis in primary infantile glaucoma and other diseases with Megalocornea is discussed.
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heterogeneity versus variability in Megalocornea mental retardation mmr syndromes report of new cases and delineation of 4 probable types
American Journal of Medical Genetics, 1993Co-Authors: Alain Verloes, H Journel, Catherine Elmer, Jeanpaul Misson, Martine Le Merrer, Josseline Kaplan, Lionel Van Maldergem, Hilde Deconinck, Françoise MeireAbstract:Megalocornea (corneal diameter ≥ 13 mm) is associated with mental and neurological impairment, and minor anomalies in Neuhauser syndrome (Megalocornea-mental retardation syndrome). Here we report 4 new cases of Megalocornea and mental retardation. Those unrelated patients have a consistent pattern of anomalies with possible recessive inheritance which clearly differs from that of the original patients of Neuhauser et al. [1975]. We discuss the heterogeneity of the syndromes with Megalocornea and mental retardation. Based on these caes and on a review of the literature, we suggest a provisional clinically oriented classification in 5 subtypes: (1) a recessive form type Neuhauser (with iris hypoplasia and minor anomalies), (2) a recessive form type Frank-Temtamy (with camptodactyly, scoliosis and growth retardation), (3) a recessive type 3 including our 4 personal cases (with normal irides, severe hypotonia, relative or absolute macrocephaly and minor anomalies), (4) a possible Frydman type (with normal irides, megalencephaly and obesity), and (5) provisionally unclassifiable cases. © 1993 Wiley-Liss, Inc.
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Autosomal Dominant Congenital Miosis with Megalocornea
Ophthalmic paediatrics and genetics, 1992Co-Authors: Françoise Meire, Jw DellemanAbstract:A family with AD congenital miosis is presented. The ocular symptoms were: Megalocornea, iris translucency, microcoria with poor pupillary dilatation and goniodysgenesis with anterior insertion of the iris. This observation confirms that in congenital miosis abnormal development of the whole anterior eye segment may occur. The patients have an increased risk to develop glaucoma. If retinoscopy is impossible due to pin-point pupils, ultrasonic biometry to determine the axial length is recommended. An optical iridectomy could improve visual performance at low illumination; the complaints of photophobia, which are related to the iris translucency, persist.
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x linked Megalocornea ocular findings and linkage analysis
Ophthalmic Paediatrics and Genetics, 1991Co-Authors: Françoise Meire, E Bleekerwagemakers, Martin K Oehler, Andreas Gal, Jw DellemanAbstract:A family with X-linked Megalocornea (XMC) is presented. The most typical ocular features of the disease (cornea globosa, arcus lipoides, mosaic dystrophy of the cornea, pigment dispersion, and cataract) are described and their diagnostic value is discussed by reviewing the literature. Linkage data suggest that the XMC locus maps in the region Xq13-q25, most probably in Xq21-q22.
Hala Hassan - One of the best experts on this subject based on the ideXlab platform.
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Association of CHRDL1 Mutations and Variants with X-linked Megalocornea, Neuhäuser Syndrome and Central Corneal Thickness
2016Co-Authors: Alice E. Davidson, Sek-shir Cheong, Pirro G. Hysi, Cristina Venturini, Vincent Plagnol, Jonathan B. Ruddle, Hala Ali, Nicole Carnt, Jessica C. Gardner, Hala HassanAbstract:We describe novel CHRDL1 mutations in ten families with X-linked Megalocornea (MGC1). Our mutation-positive cohort enabled us to establish ultrasonography as a reliable clinical diagnostic tool to distinguish between MGC1 and primary congenital glaucoma (PCG). Megalocornea is also a feature of Neuhäuser or Megalocornea-mental retardation (MMR) syndrome, a rare condition of unknown etiology. In a male patient diagnosed with MMR, we performed targeted and whole exome sequencing (WES) and identified a novel missense mutation in CHRDL1 that accounts for his MGC1 phenotype but not his non-ocular features. This finding suggests that MMR syndrome, in some cases, may be di- or multigenic. MGC1 patients have reduced central corneal thickness (CCT); however no X-linked loci have been associated with CCT, possibly because the majority of genome-wide association studies (GWAS) overlook the X-chromosome. We therefore explored whether variants on the X-chromosome are associated with CCT. We found rs149956316, in intron 6 of CHRDL1, to be th
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association of chrdl1 mutations and variants with x linked Megalocornea neuhauser syndrome and central corneal thickness
PLOS ONE, 2014Co-Authors: Alice E. Davidson, Sek-shir Cheong, Pirro G. Hysi, Cristina Venturini, Vincent Plagnol, Jonathan B. Ruddle, Hala Ali, Nicole Carnt, Jessica C. Gardner, Hala HassanAbstract:We describe novel CHRDL1 mutations in ten families with X-linked Megalocornea (MGC1). Our mutation-positive cohort enabled us to establish ultrasonography as a reliable clinical diagnostic tool to distinguish between MGC1 and primary congenital glaucoma (PCG). Megalocornea is also a feature of Neuhauser or Megalocornea-mental retardation (MMR) syndrome, a rare condition of unknown etiology. In a male patient diagnosed with MMR, we performed targeted and whole exome sequencing (WES) and identified a novel missense mutation in CHRDL1 that accounts for his MGC1 phenotype but not his non-ocular features. This finding suggests that MMR syndrome, in some cases, may be di- or multigenic. MGC1 patients have reduced central corneal thickness (CCT); however no X-linked loci have been associated with CCT, possibly because the majority of genome-wide association studies (GWAS) overlook the X-chromosome. We therefore explored whether variants on the X-chromosome are associated with CCT. We found rs149956316, in intron 6 of CHRDL1, to be the most significantly associated single nucleotide polymorphism (SNP) (p = 6.81×10(-6)) on the X-chromosome. However, this association was not replicated in a smaller subset of whole genome sequenced samples. This study highlights the importance of including X-chromosome SNP data in GWAS to identify potential loci associated with quantitative traits or disease risk.
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Novel CHRDL1 missense mutation in a patient diagnosed with MMR.
2014Co-Authors: Alice E. Davidson, Sek-shir Cheong, Pirro G. Hysi, Cristina Venturini, Vincent Plagnol, Jonathan B. Ruddle, Hala Ali, Nicole Carnt, Jessica C. Gardner, Hala HassanAbstract:(A) Pedigree of Family K with Megalocornea-mental retardation (MMR) syndrome. Squares, males; circles, females; diamonds, unknown gender; shaded, affected; dotted, carrier; clear, unaffected. Arrowhead indicates proband. Sequence electropherograms show the CHRDL1 missense mutation c.464G>A; p.(Cys155Tyr), which segregates in Family K. (B–C) The proband at ages 3, and 6 years, respectively, presented with bilateral Megalocorneae, broad forehead, bilateral epicanthic folds, a tented upper lip, and downturned corners of the mouth. (D–E) Frontal and sides of the proband at age of 10 years.
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Comparison between biometry of X-linked Megalocornea and congenital glaucoma.
2014Co-Authors: Alice E. Davidson, Sek-shir Cheong, Pirro G. Hysi, Cristina Venturini, Vincent Plagnol, Jonathan B. Ruddle, Hala Ali, Nicole Carnt, Jessica C. Gardner, Hala HassanAbstract:(A) AC, anterior chamber depth (back of cornea to front of lens); AL, axial length (anterior corneal surface to vitreo-retinal interface at the back of the macular). Transverse B-Mode ultrasound scans demonstrate higher ratio of the AC to AL in Megalocornea, 0.204 (left) than congenital glaucoma, 0.135 (right). (B) Ocular coherence tomography (OCT) images comparing Megalocornea (left) and arrested congenital glaucoma (right). Although there is enlargement of the anterior segment in both conditions, patients with Megalocornea tend to have a greater anterior chamber (AC) depth, lower central corneal thickness (CCT), and deeper anterior chamber angles (ACA) than congenital glaucoma patients.
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Summary of CHRDL1 mutations.
2014Co-Authors: Alice E. Davidson, Sek-shir Cheong, Pirro G. Hysi, Cristina Venturini, Vincent Plagnol, Jonathan B. Ruddle, Hala Ali, Nicole Carnt, Jessica C. Gardner, Hala HassanAbstract:(A) Schematic of CHRDL1 protein domains. The following abbreviations are used: SP, signal peptide; VWFC, von Willebrand factor, type C domain. (B) Schematic of the CHRDL1 gene. (C) CHRDL1 mutations previously reported in X-linked Megalocornea families [3], [6]. Frameshift, splicing, nonsense, missense, and whole gene deletion mutations were identified. (D) Novel CHRDL1 mutations identified in MGC1 families in this study (Families A–J). The dagger (†) indicates Family K with MMR syndrome.
R M Goodman - One of the best experts on this subject based on the ideXlab platform.
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Megalocornea macrocephaly mental and motor retardation mmmm
Clinical Genetics, 2008Co-Authors: Moshe Frydman, Michal Berkenstadt, A Raasrothschild, R M GoodmanAbstract:Two patients with macrocephaly, mild mental retardation and Megalocornea are reported. Hypotonia, poor coordination and swallowing difficulties were present. One patient was obese and the other had scoliosis. Both had large fleshy ears and long fingers. The spectrum of the mental retardation Megalocornea syndrome is not fully defined. These two patients resemble a previously reported case, and although there are distinct differences from patients with familial or sporadic Neuhauser syndrome, these cases may represent clinical variability of that syndrome.
L Zergollern - One of the best experts on this subject based on the ideXlab platform.
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Megalocornea-mental retardation syndrome: report of a new case.
Journal of medical genetics, 1996Co-Authors: Ingeborg Barišić, I Ligutić, L ZergollernAbstract:Megalocornea-mental retardation syndrome (MMR) is a rare autosomal recessive disorder presenting with Megalocornea, mental and motor retardation, hypotonia, seizures, short stature, and characteristic dysmorphic traits (MIM 249310). We present a new case in order to delineate with more accuracy the typical phenotype.
Alice E. Davidson - One of the best experts on this subject based on the ideXlab platform.
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Association of CHRDL1 Mutations and Variants with X-linked Megalocornea, Neuhäuser Syndrome and Central Corneal Thickness
2016Co-Authors: Alice E. Davidson, Sek-shir Cheong, Pirro G. Hysi, Cristina Venturini, Vincent Plagnol, Jonathan B. Ruddle, Hala Ali, Nicole Carnt, Jessica C. Gardner, Hala HassanAbstract:We describe novel CHRDL1 mutations in ten families with X-linked Megalocornea (MGC1). Our mutation-positive cohort enabled us to establish ultrasonography as a reliable clinical diagnostic tool to distinguish between MGC1 and primary congenital glaucoma (PCG). Megalocornea is also a feature of Neuhäuser or Megalocornea-mental retardation (MMR) syndrome, a rare condition of unknown etiology. In a male patient diagnosed with MMR, we performed targeted and whole exome sequencing (WES) and identified a novel missense mutation in CHRDL1 that accounts for his MGC1 phenotype but not his non-ocular features. This finding suggests that MMR syndrome, in some cases, may be di- or multigenic. MGC1 patients have reduced central corneal thickness (CCT); however no X-linked loci have been associated with CCT, possibly because the majority of genome-wide association studies (GWAS) overlook the X-chromosome. We therefore explored whether variants on the X-chromosome are associated with CCT. We found rs149956316, in intron 6 of CHRDL1, to be th
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association of chrdl1 mutations and variants with x linked Megalocornea neuhauser syndrome and central corneal thickness
PLOS ONE, 2014Co-Authors: Alice E. Davidson, Sek-shir Cheong, Pirro G. Hysi, Cristina Venturini, Vincent Plagnol, Jonathan B. Ruddle, Hala Ali, Nicole Carnt, Jessica C. Gardner, Hala HassanAbstract:We describe novel CHRDL1 mutations in ten families with X-linked Megalocornea (MGC1). Our mutation-positive cohort enabled us to establish ultrasonography as a reliable clinical diagnostic tool to distinguish between MGC1 and primary congenital glaucoma (PCG). Megalocornea is also a feature of Neuhauser or Megalocornea-mental retardation (MMR) syndrome, a rare condition of unknown etiology. In a male patient diagnosed with MMR, we performed targeted and whole exome sequencing (WES) and identified a novel missense mutation in CHRDL1 that accounts for his MGC1 phenotype but not his non-ocular features. This finding suggests that MMR syndrome, in some cases, may be di- or multigenic. MGC1 patients have reduced central corneal thickness (CCT); however no X-linked loci have been associated with CCT, possibly because the majority of genome-wide association studies (GWAS) overlook the X-chromosome. We therefore explored whether variants on the X-chromosome are associated with CCT. We found rs149956316, in intron 6 of CHRDL1, to be the most significantly associated single nucleotide polymorphism (SNP) (p = 6.81×10(-6)) on the X-chromosome. However, this association was not replicated in a smaller subset of whole genome sequenced samples. This study highlights the importance of including X-chromosome SNP data in GWAS to identify potential loci associated with quantitative traits or disease risk.
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Novel CHRDL1 missense mutation in a patient diagnosed with MMR.
2014Co-Authors: Alice E. Davidson, Sek-shir Cheong, Pirro G. Hysi, Cristina Venturini, Vincent Plagnol, Jonathan B. Ruddle, Hala Ali, Nicole Carnt, Jessica C. Gardner, Hala HassanAbstract:(A) Pedigree of Family K with Megalocornea-mental retardation (MMR) syndrome. Squares, males; circles, females; diamonds, unknown gender; shaded, affected; dotted, carrier; clear, unaffected. Arrowhead indicates proband. Sequence electropherograms show the CHRDL1 missense mutation c.464G>A; p.(Cys155Tyr), which segregates in Family K. (B–C) The proband at ages 3, and 6 years, respectively, presented with bilateral Megalocorneae, broad forehead, bilateral epicanthic folds, a tented upper lip, and downturned corners of the mouth. (D–E) Frontal and sides of the proband at age of 10 years.
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Comparison between biometry of X-linked Megalocornea and congenital glaucoma.
2014Co-Authors: Alice E. Davidson, Sek-shir Cheong, Pirro G. Hysi, Cristina Venturini, Vincent Plagnol, Jonathan B. Ruddle, Hala Ali, Nicole Carnt, Jessica C. Gardner, Hala HassanAbstract:(A) AC, anterior chamber depth (back of cornea to front of lens); AL, axial length (anterior corneal surface to vitreo-retinal interface at the back of the macular). Transverse B-Mode ultrasound scans demonstrate higher ratio of the AC to AL in Megalocornea, 0.204 (left) than congenital glaucoma, 0.135 (right). (B) Ocular coherence tomography (OCT) images comparing Megalocornea (left) and arrested congenital glaucoma (right). Although there is enlargement of the anterior segment in both conditions, patients with Megalocornea tend to have a greater anterior chamber (AC) depth, lower central corneal thickness (CCT), and deeper anterior chamber angles (ACA) than congenital glaucoma patients.
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Summary of CHRDL1 mutations.
2014Co-Authors: Alice E. Davidson, Sek-shir Cheong, Pirro G. Hysi, Cristina Venturini, Vincent Plagnol, Jonathan B. Ruddle, Hala Ali, Nicole Carnt, Jessica C. Gardner, Hala HassanAbstract:(A) Schematic of CHRDL1 protein domains. The following abbreviations are used: SP, signal peptide; VWFC, von Willebrand factor, type C domain. (B) Schematic of the CHRDL1 gene. (C) CHRDL1 mutations previously reported in X-linked Megalocornea families [3], [6]. Frameshift, splicing, nonsense, missense, and whole gene deletion mutations were identified. (D) Novel CHRDL1 mutations identified in MGC1 families in this study (Families A–J). The dagger (†) indicates Family K with MMR syndrome.