X-linked megalocornea: close linkage to DXS87 and DXS94

Chen, J. D.; Mackey, David A.; Fuller, H.; Serravalle, S.; Olsson, Jane E.; Denton, M. J.

doi:10.1007/bf00285176

Cited by 35 publications

(8 citation statements)

References 3 publications

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“…The recent isolation and physical mapping of a YAC containing the a-galactosidase A gene indicated it was in Xq22.1 approximately 70 kb from the ATK gene (Vetrie et al, 199313). Of interest, several other genetic disorders have been localized to Xq22 by linkage analysis in large pedigrees, including a megalocornea syndrome (Chen et al, 1989).…”

Section: The Molecular Genetics Of A-galactosidase Amentioning

confidence: 99%

Molecular basis of fabry disease: Mutations and polymorphisms in the human α-galactosidase A gene

Eng

Desnick²

1994

Hum. Mutat.

130

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Fabry disease, an X-linked inborn error of glycosphingolipid catabolism, results from mutations in the alpha-galactosidase A gene at Xq22.1. Studies of the mutations in unrelated Fabry families have identified a variety of lesions indicating the molecular genetic heterogeneity underlying the disease. Forty-nine different mutations have been described including five partial gene deletions, one partial gene duplication, nine small deletions and insertions, three splice junction consensus site alterations, and 31 coding region single base substitutions. Most mutations resulted in the classical disease phenotype; however, five missense mutations were detected in atypical hemizygotes who were asymptomatic or had symptoms confined to the heart, including N215S, which was described in three unrelated atypical males. Most mutations were confined to a single pedigree with the exception of N215S, R227Q, R227X, R342Q, and R342X, which were each found in several unrelated families. Five of the 14 coding region CpG dinucleotides were sites of point mutations including the CpGs in codons 227 and 342, which were each mutated in both orientations. The identification of the mutation in a given Fabry family permits precise prenatal diagnosis and heterozygote detection of other family members with this X-linked recessive disease. Studies of additional Fabry families will provide information on the nature and frequency of the mutations causing this disease as well as potential insights into the structure/function relationships of this lysosomal hydrolase.

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Section: The Molecular Genetics Of A-galactosidase Amentioning

confidence: 99%

Molecular basis of fabry disease: Mutations and polymorphisms in the human α-galactosidase A gene

Eng

Desnick²

1994

Hum. Mutat.

130

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“…Other secondary changes include mosaic corneal degeneration (shagreen), corneal arcus juvenilis, lens dislocation and mild iris atrophy with pigment dispersion [3]. The condition was genetically linked to the long arm of the X-chromosome over twenty years ago (Xq12-q26; MGC1) [2], [4] but the underlying genetic cause, mutations in CHRDL1 (MIM 300350), has only recently been discovered [3]. CHRDL1 encodes ventroptin (or neuralin-1, neurogenesin-1, chordin-like 1), a secreted bone morphogenetic protein (BMP) antagonist [5].…”

Section: Introductionmentioning

confidence: 99%

Association of CHRDL1 Mutations and Variants with X-linked Megalocornea, Neuhäuser Syndrome and Central Corneal Thickness

Davidson¹,

Cheong²,

Hysi

et al. 2014

PLoS ONE

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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 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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“…Arcus lipoides, mosaic corneal dystrophy, pigment dispersion, cataract, and lens dislocation are associated ocular anomalies in the disease; those symptoms are age-related.3 4 The gene for X linked megalocornea has been mapped on the long arm of the X chromosome. [3][4][5] In this study we performed a biometric examination in 11 affected males. The importance of biometric data for diagnosis and for differential diagnosis with primary infantile glaucoma and other diseases with megalocornea is discussed.…”

mentioning

confidence: 99%

Biometry in X linked megalocornea: pathognomonic findings.

Meire

Delleman

1994

British Journal of Ophthalmology

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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. (Br3 Ophthalmol 1994; 78: 781-785)

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X-linked megalocornea: close linkage to DXS87 and DXS94

Abstract: In a family in which X-linked megalocornea is segregating, the disease locus was found to be closely linked to DXS87 (zeta max = 3.91, theta max = 0.00) and DXS94 (zeta max = 3.34, theta max = 0.00) in Xq21.3-q22.

Cited by 35 publications

References 3 publications

Molecular basis of fabry disease: Mutations and polymorphisms in the human α-galactosidase A gene

Molecular basis of fabry disease: Mutations and polymorphisms in the human α-galactosidase A gene

Association of CHRDL1 Mutations and Variants with X-linked Megalocornea, Neuhäuser Syndrome and Central Corneal Thickness

Biometry in X linked megalocornea: pathognomonic findings.

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