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BMJ Case Reports Apr 2016A 16-year-old boy presented with decrease of vision over a period of 2 years. On examination, he was diagnosed to have microspherophakia with lenticular myopia with...
A 16-year-old boy presented with decrease of vision over a period of 2 years. On examination, he was diagnosed to have microspherophakia with lenticular myopia with secondary glaucoma in both eyes. He was treated by lens aspiration and two-point capsular support using a modified capsular tension ring (M-CTR) and capsular tension segment (CTS) sutured to the sclera along with implantation of a foldable intraocular lens inside the bag. Lens aspiration was performed without artificial capsular hook support of the bag, as the lens was soft and vitreous was formed. However, M-CTR rotation into the bag was fraught with repeated adherence of the advancing end of the M-CTR into the loose bag causing simultaneous rotation of the bag with the rotation of the ring resulting in transient increase in bag subluxation. Capsular hooks provided appropriate countertraction to the unsupported bag, thus facilitating easy insertion and rotation of the ring into the bag.
Topics: Adolescent; Corneal Diseases; Ectopia Lentis; Glaucoma; Humans; Iris; Lens Capsule, Crystalline; Lens Implantation, Intraocular; Lens Subluxation; Lenses, Intraocular; Male; Microsurgery; Myopia; Phacoemulsification; Sclera
PubMed: 27048263
DOI: 10.1136/bcr-2015-214274 -
Risk Management and Healthcare Policy 2021Weill-Marchesani syndrome (WMS) is an autosomal inherited connective tissue disease. Clinical manifestations include microspherophakia (MSP), high myopia, ectopia...
BACKGROUND
Weill-Marchesani syndrome (WMS) is an autosomal inherited connective tissue disease. Clinical manifestations include microspherophakia (MSP), high myopia, ectopia lentis, open-angle glaucoma, short stature, short fingers, joint stiffness, and (occasionally) cardiovascular defects. At present, a total of four pathogenic gene loci related to WMS have been found: ADAMTS10, ADAMTS17, FBN1, and LTBP2.
CASE REPORT
The patient was a five-year-old girl whose eyesight had become progressively worse for three years before her parents brought her to the hospital. Computer optometry showed high myopia in both eyes, while a slit lamp examination found that the anterior chamber of both eyes was shallow, and the lens was in a state of dislocation (ectopia lentis). An IOLMaster examination revealed that the lens was spherical (MSP), and the lens thickness (LT) was 5.36 mm. Corneal topography showed that the angle kappa was 0.18 mm in the right eye (OD) and 0.30 mm in the left eye (OS). An intraocular pressure (IOP) (OD: 26.5 mmHg, OS: 30.6 mmHg) examination showed that the fundus cup to disc ratio was normal, but secondary glaucoma caused by lens dislocation could be considered. The IOP was maintained within a normal range using antihypertensive drugs. The patient's younger sister also had a dislocation of MSP. Gene detection showed a heterozygous mutation in the LTBP2 gene [c.3672delC:p.Thr1225fs and c.3542delT:p.Met1181fs], and a diagnosis of WMS-like syndrome was confirmed.
CONCLUSION
WMS syndrome is rare, and the mutation of the LTBP2 gene has not been previously recorded in the GnomAD (Genome Aggregation Database) of East Asia. This case report provides some reference for studying the mechanism of WMS and WMS-like syndrome caused by an LTBP2 gene mutation.
PubMed: 33958902
DOI: 10.2147/RMHP.S307290 -
European Journal of Human Genetics :... Sep 2015Weill-Marchesani syndrome is a rare disorder of the connective tissue. Functional variants in ADAMTS10 are associated with Weill-Marchesani syndrome-1. We identified a...
Weill-Marchesani syndrome is a rare disorder of the connective tissue. Functional variants in ADAMTS10 are associated with Weill-Marchesani syndrome-1. We identified a homozygous missense mutation, c.41T>A, of the ADAMTS10 gene in a 19-year-old female with typical symptoms of WMS1: proportionate short stature, brachydactyly, joint stiffness, and microspherophakia. The ADAMTS10 missense mutation was analysed in silico, with conflicting results as to its effects on protein function, but it was predicted to affect the leader sequence. Molecular characterisation in HEK293 Ebna cells revealed an intracellular mis-targeting of the ADAMTS10 protein with a reduced concentration of the polypeptide in the endoplasmic reticulum. A large reduction in glycosylation of the cytoplasmic fraction of the mutant ADAMTS10 protein versus the wild-type protein and a lack of secretion of the mutant protein are also evident in our results.In conclusion, we identified a novel missense mutation of the ADAMTS10 gene and confirmed the functional consequences suggested by the in silico analysis by conducting molecular studies.
Topics: Female; Humans; Young Adult; ADAM Proteins; ADAMTS Proteins; Amino Acid Sequence; Base Sequence; Computer Simulation; Endoplasmic Reticulum; Gene Expression; Genotype; Glycosylation; HEK293 Cells; Homozygote; Molecular Sequence Data; Mutation, Missense; Pedigree; Phenotype; Protein Transport; Sequence Analysis, DNA; Weill-Marchesani Syndrome
PubMed: 25469541
DOI: 10.1038/ejhg.2014.264 -
Indian Journal of Ophthalmology Jun 2020
Topics: Corneal Diseases; Ectopia Lentis; Glaucoma; Humans; Iris; Lens Subluxation; Lens, Crystalline
PubMed: 32461458
DOI: 10.4103/ijo.IJO_1898_19 -
Human Molecular Genetics Nov 2014Latent TGF-β-binding protein-2 (LTBP-2) is an extracellular matrix protein associated with microfibrils. Homozygous mutations in LTBP2 have been found in humans with...
Latent TGF-β-binding protein-2 (LTBP-2) is an extracellular matrix protein associated with microfibrils. Homozygous mutations in LTBP2 have been found in humans with genetic eye diseases such as congenital glaucoma and microspherophakia, indicating a critical role of the protein in eye development, although the function of LTBP-2 in vivo has not been well understood. In this study, we explore the in vivo function of LTBP-2 by generating Ltbp2(-/-) mice. Ltbp2(-/-) mice survived to adulthood but developed lens luxation caused by compromised ciliary zonule formation without a typical phenotype related to glaucoma, suggesting that LTBP-2 deficiency primarily causes lens dislocation but not glaucoma. The suppression of LTBP2 expression in cultured human ciliary epithelial cells by siRNA disrupted the formation of the microfibril meshwork by the cells. Supplementation of recombinant LTBP-2 in culture medium not only rescued the microfibril meshwork formation in LTBP2-suppressed ciliary epithelial cells but also restored unfragmented and bundled ciliary zonules in Ltbp2(-/-) mouse eyes under organ culture. Although several reported human mutant LTBP-2 proteins retain normal domain structure and keep the fibrillin-1-binding site intact, none of these mutant proteins were secreted from their producing cells, suggesting secretion arrest occurred to the LTBP-2 mutants owing to conformational alteration. The findings of this study suggest that LTBP-2 is an essential component for the formation of microfibril bundles in ciliary zonules.
Topics: Animals; Cell Line; Cilia; Ectopia Lentis; Epithelial Cells; Fibrillin-1; Fibrillins; Gene Knockout Techniques; Gene Targeting; Genotype; Glaucoma; Humans; Latent TGF-beta Binding Proteins; Mice; Mice, Knockout; Microfibrils; Microfilament Proteins; Mutation; Phenotype; Protein Binding
PubMed: 24908666
DOI: 10.1093/hmg/ddu283 -
International Journal of Molecular... May 2023Weill-Marchesani syndrome (WMS) is a rare genetic inherited disorder with autosomal recessive and dominant modes of inheritance. WMS is characterized by the association...
A Novel Mutation in the Associated with Weil-Marchesani Syndrome with a Unique Presentation of Developed Membranes Causing Severe Stenosis of the Supra Pulmonic, Supramitral, and Subaortic Areas in the Heart.
Weill-Marchesani syndrome (WMS) is a rare genetic inherited disorder with autosomal recessive and dominant modes of inheritance. WMS is characterized by the association of short stature, brachydactyly, joint stiffness, eye anomalies, including microspherophakia and ectopia of the lenses, and, occasionally, heart defects. We investigated the genetic cause of a unique and novel presentation of heart-developed membranes in the supra-pulmonic, supramitral, and subaortic areas, creating stenosis that recurred after their surgical resection in four patients from one extended consanguineous family. The patients also presented ocular findings consistent with Weill-Marchesani syndrome (WMS). We used whole exome sequencing (WES) to identify the causative mutation and report it as a homozygous nucleotide change c. 232T>C causing p. Tyr78His in . (ADAM Metallopeptidase with Thrombospondin Type 1 Motif 10) is a member of a family of zinc-dependent extracellular matrix protease family. This is the first report of a mutation in the pro-domain of . The novel variation replaces a highly evolutionary conserved tyrosine with histidine. This change may affect the secretion or function of ADAMTS10 in the extracellular matrix. The compromise in protease activity may thus cause the unique presentation of the developed membranes in the heart and their recurrence after surgery.
PubMed: 37240210
DOI: 10.3390/ijms24108864 -
Indian Journal of Ophthalmology Apr 2020A lady who underwent lensectomy for microspherophakia and pars plana vitrectomy for retinal detachment in her left eye developed recurrent filtering blebs at the site of...
A lady who underwent lensectomy for microspherophakia and pars plana vitrectomy for retinal detachment in her left eye developed recurrent filtering blebs at the site of sclerotomies. Filtering blebs were managed by suturing the sclerotomies. Targeted gene sequencing identified a variant of ASPH gene (p.Arg688Gln) which is not known to be associated with Traboulsi syndrome. But considering the paucity of cases with genetic analysis, it would be possible that p.Arg688Gln is a pathogenic variant. This is the first case report of Traboulsi syndrome due to an ASPH variant not reported earlier that can lead to recurrent filtering blebs.
Topics: Female; Humans; Ectopia Lentis; Glaucoma; Retinal Detachment; Retrospective Studies; Vitrectomy
PubMed: 32174599
DOI: 10.4103/ijo.IJO_1249_19