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JPMA. the Journal of the Pakistan... Mar 2020Latent transforming growth factor beta binding protein 2 (LTBP2) plays a critical role in the development of connective tissue structure and function. Mutations in gene...
Latent transforming growth factor beta binding protein 2 (LTBP2) plays a critical role in the development of connective tissue structure and function. Mutations in gene encoding LTBP2 are known to cause syndromic and a non-syndromic microspherophakia. Here, we present a 'first' report of genetic linkage of microspherophakia (MSP) to LTBP2 locus in a large consanguineous Pakistani family with four affected individuals in three loops. Using polymorphic microsatellite markers, haplotypes and linkage analysis, the diseased phenotype in MSP001 family was mapped to the LTBP2 gene. A maximum two point Logarithm of the odds (LOD) score of 4.16 was obtained with marker D14S284 at θ =0. Mutational analysis of exon 36 of LTBP2 using Sanger's sequencing did not reveal any previously reported mutations. Further analysis of the remaining exons are required to identify the causative variant.
Topics: Adolescent; Chromosome Mapping; Chromosomes, Human, Pair 14; Consanguinity; Corneal Diseases; Ectopia Lentis; Female; Glaucoma; Humans; Iris; Latent TGF-beta Binding Proteins; Lens Subluxation; Male; Medical History Taking; Mutation; Myopia; Pakistan; Pedigree; Young Adult
PubMed: 32207437
DOI: 10.5455/JPMA.302440 -
Frontiers in Genetics 2022Geleophysic dysplasia and Weill-Marchesani syndrome from the acromelic dysplasias group of genetic skeletal disorders share remarkable clinical and genetic overlap....
Geleophysic dysplasia and Weill-Marchesani syndrome from the acromelic dysplasias group of genetic skeletal disorders share remarkable clinical and genetic overlap. Ophthalmological, physical, radiological examinations were conducted with a female patient in her early 30 s. Whole exome sequencing followed by Sanger sequencing validation was performed to identify the genetic cause. The patient, born to consanguineous Chinese parents, presented with microspherophakia, lens subluxation, high myopia, short statue, small hands and feet, stiff joints, and thickened skin. A diagnosis of Weill-Marchesani syndrome was initially made for her. However, genetic testing reveals that the patient is homozygous for the c.1966G>A (p.Gly656Ser) variant in , and that the patient's healthy mother and daughter are heterozygous for the variant. As mutations in are known to cause autosomal recessive geleophysic dysplasia, the patient is re-diagnosed with geleophysic dysplasia in terms of her genotype and phenotype. The present study describes the clinical phenotype of the homozygous p. Gly656Ser variant, which increases our understanding of the genotype-phenotype correlation in acromelic dysplasias.
PubMed: 36246610
DOI: 10.3389/fgene.2022.1014188 -
Indian Journal of Ophthalmology 2007Retinitis pigmentosa (RP) is associated with a wide variety of ocular and systemic disorders. The Weill-Marchesani syndrome is a multi-system disorder with...
Retinitis pigmentosa (RP) is associated with a wide variety of ocular and systemic disorders. The Weill-Marchesani syndrome is a multi-system disorder with microspherophakia as one of the common manifestations. A 14-year-old girl presented with short stature, short and stubby fingers, hypodontia and low-set ears. Slit-lamp examination revealed microspherophakia, with shallow anterior chambers with irido and phacodonesis. Ultrasonographic biomicroscopy confirmed the clinical findings and revealed hypoplastic ciliary body. Electroretinogram confirmed the diagnosis of RP. Though RP has been associated with ectopia lentis in earlier reports, this is, to the best of our knowledge, the first case report describing the association of RP and Weill-Marchesani syndrome.
Topics: Abnormalities, Multiple; Adolescent; Diagnosis, Differential; Dwarfism; Electroretinography; Female; Fingers; Glaucoma, Angle-Closure; Hand Deformities, Congenital; Humans; Lens Subluxation; Microscopy, Acoustic; Myopia; Prognosis; Retinitis Pigmentosa; Syndrome
PubMed: 17322607
DOI: 10.4103/0301-4738.30711 -
Trauma Case Reports Dec 2023We report a case of traumatic bleb leak following trabeculectomy and dislocated intraocular lens treated with combined minimally invasive conjunctival surgery (MICS) and...
PURPOSE
We report a case of traumatic bleb leak following trabeculectomy and dislocated intraocular lens treated with combined minimally invasive conjunctival surgery (MICS) and lens repositioning.
OBSERVATIONS
A 36-year-old woman with a history of phacomorphic glaucoma secondary to microspherophakia and status post trabeculectomy underwent combined MICS and lens repositioning for a late-onset bleb leak and dislocated intraocular lens following minor trauma. The patient's vision rapidly improved postoperatively with prompt resolution of hypotony.
CONCLUSION/IMPORTANCE
MICS is an effective treatment for traumatic bleb leak following trabeculectomy that can be a particularly useful approach for patients undergoing concurrent ophthalmic surgery.
PubMed: 37810536
DOI: 10.1016/j.tcr.2023.100936 -
Journal of Medical Genetics Jan 2003Weill-Marchesani syndrome (WMS) is a connective tissue disorder characterised by short stature, brachydactyly, joint stiffness, and characteristic eye anomalies...
Weill-Marchesani syndrome (WMS) is a connective tissue disorder characterised by short stature, brachydactyly, joint stiffness, and characteristic eye anomalies including microspherophakia, ectopia of the lenses, severe myopia, and glaucoma. Both autosomal recessive (AR) and autosomal dominant (AD) modes of inheritance have been described and a gene for AR WMS has recently been mapped to chromosome 19p13.3-p13.2. Here, we report on the exclusion of chromosome 19p13.3-p13.2 in a large AD WMS family and show that, despite clinical homogeneity, AD and AR WMS are genetically heterogeneous entities. Because two AD WMS families were consistent with linkage to chromosome 15q21.1, the fibrillin-1 gene was sequenced and a 24 nt in frame deletion within a latent transforming growth factor-beta1 binding protein (LTBP) motif of the fibrillin-1 gene was found in a AD WMS family (exon 41, 5074_5097del). This in frame deletion cosegregated with the disease and was not found in 186 controls. This study strongly suggests that AD WMS and Marfan syndrome are allelic conditions at the fibrillin-1 locus and adds to the remarkable clinical heterogeneity of type I fibrillinopathies.
Topics: Abnormalities, Multiple; Adolescent; Adult; Child; Child, Preschool; Extracellular Matrix Proteins; Eye Abnormalities; Female; Fibrillin-1; Fibrillins; Gene Deletion; Genes, Dominant; Growth Disorders; Humans; Limb Deformities, Congenital; Male; Marfan Syndrome; Microfilament Proteins; Middle Aged; Pedigree; Reading Frames; Syndrome
PubMed: 12525539
DOI: 10.1136/jmg.40.1.34 -
The National Medical Journal of India 2019
Topics: Child; Corneal Diseases; Ectopia Lentis; Female; Glaucoma; Humans; Iris; Lens, Crystalline
PubMed: 32769256
DOI: 10.4103/0970-258X.291302 -
Indian Journal of Ophthalmology Nov 2014
PubMed: 25494262
DOI: 10.4103/0301-4738.146738 -
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