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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 -
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 -
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 -
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