Congenital cataract: An ocular manifestation of classical homocystinuria

Saba, Neelam; Irshad, Saba

doi:10.1002/mgg3.1742

Cited by 6 publications

(2 citation statements)

References 19 publications

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“…Regarding patients with monogenetic methylation disorders, studies on patients with MTHFR 20 and CBS deficiency 21,22 reported ectopia lentis, congenital cataract, 23 and myopia as commonly observed ophthalmological features. One patient with CBS in our cohort showed ectopia lentis, while it was not reported for any patient affected by MTHFR.…”

Section: Discussionmentioning

confidence: 99%

Methylation-associated pathways in Macular Telangiectasia Type 2 and ophthalmologic findings in patients with genetic methylation disorders

Pauleikhoff,

Wingert,

Grünert

et al. 2024

Retina

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Purpose: Serine (Ser) and glycine (Gly) levels were reported to differ between Macular telangiectasia type 2 (MacTel) patients compared to healthy controls. Since they are closely related to methylation metabolism, this report investigates methylation-associated metabolite (MAM) levels in MacTel patients and retinal changes in monogenetic methylation disorders. Methods: Prospective, monocentric study on MacTel patients and healthy controls the underwent a standardized protocol including a blood draw. MAM levels in plasma were determined using targeted quantitative metabolomics. Furthermore, patient records of cystathionine beta-synthase (CBS), methylenetetrahydrofolate reductase (MTHFR), and cobalamin C (MMACHC) deficiency were screened for reported retinal changes. Results: In total, 29 MacTel patients and 27 healthy controls were included. MacTel patients showed lower plasma Ser (p = 0.02 and p = 0.01) and Gly (p= 0.11 and p = 0.11) levels than controls. Principal component analyses revealed that MAM, especially homocysteine, contributed to a distinct clustering of MacTel patients. No retinal changes were seen in CBS (n=1) and MTHFR (n=2) deficiency, while two patients with MMACHC (n=4) deficiency displayed extensive macular dystrophy. Conclusions: MacTel patients show distinct clustering of MAM compared to controls. Of the three homocystinurias, only MMACHC resulted in macular dystrophy, possibly due to distinct compensatory pathways.

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Section: Discussionmentioning

confidence: 99%

Methylation-associated pathways in Macular Telangiectasia Type 2 and ophthalmologic findings in patients with genetic methylation disorders

Pauleikhoff,

Wingert,

Grünert

et al. 2024

Retina

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show abstract

“…Only nine patients were identified with homocystinuria, and none had c.833T>C mutation [ 22 ]. A study on three patients in a Pakistani consanguineous family with symptoms in 2021 confirmed homocystinuria was not detected with c.833T>C mutation [ 23 ]. Although the prevalence of c.833T>C is likely less among the Asian population, but it is the most prevalent mutation worldwide in the CBS gene related to homocystinuria, thus, it is important to find out the presence and prevalence of this mutation in Sri Lanka.…”

Section: Discussionmentioning

confidence: 99%

Association of selected genetic variants in CBS and MTHFR genes in a cohort of children with homocystinuria in Sri Lanka

Samarasinghe

Mahaliyanage

Silva

et al. 2022

Journal of Genetic Engineering and Biotechnology

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Background Homocystinuria is an inherited, inborn error of homocysteine metabolism, which leads to the abnormal accumulation of homocysteine and its metabolites in blood and urine, resulting in various complications. Variants in the cystathionine β-synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR) genes interrupt the formation of the corresponding enzymes and prevent homocysteine from being metabolised; hence, the homocysteine levels in plasma increase than the optimum levels. Materials and methods In the current study, eight clinically confirmed children with homocystinuria were detected to study the chosen variants in the CBS gene (c.833 T>C and c.19del) and in the MTHFR gene (c.665 C>T, c.1286 A>C) using SNaPshot mini-sequencing and direct sequencing. Results After screening eight patients, none had the c.833T>C, but four patients were in the homozygous state for the c.19del variant in the CBS gene. Furthermore, seven were heterozygous for c.1286A>C, while one patient was heterozygous for c.665C>T in the MTHFR gene. Conclusion According to the results, c.19del is common in the studied cohort of Sri Lankan children, while c.833T>C is absent, whereas c.1286A>C was more frequent than c.665C>T. To our knowledge, the current study was the first report to discuss the genetic impact of homocystinuria in Sri Lanka; further comprehensive studies are necessary with a larger sample size to establish the association of these variants with the disease in Sri Lanka, which can be beneficial in enhanced patient care and for prospective studies.

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Congenital cataract: An ocular manifestation of classical homocystinuria

Saba

Irshad

2021

Molec Gen & Gen Med

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Background Homocystinuria is an autosomal recessive metabolic disorder occurring due to the defects in cystathionine‐β‐synthase enzyme. The study was carried out to investigate a Pakistani family presenting bilateral congenital cataract with symptoms of classical homocystinuria at LRBT Free Eye Hospital, Lahore, Pakistan. Methods Three affected individuals of the family presented skeletal deformations, intellectual disability, speech delay, and myopia with bilateral congenital cataract. Genetic analysis on DNA samples from affected individuals was done through whole exome sequencing to identify underlying genetic variant causing disease phenotypes in the family. In silico analysis was done to predict the effect of variation on the structure of mutant protein. Results A missense allelic variant (NM_000071.3: c.253G>A) of the CBS gene was revealed which may affect the catalytic activity of the substituted (NP_000062.1: p.G85R) protein by disrupting the folding of the enzymatic protein. High levels of homocysteine were observed in the plasma of affected individuals. This is the first report of this genetic variant from Pakistan causing homocystinuria and congenital cataract in association. Conclusion This variant was reported first time in association with congenital cataract instead of ectopia lentis. Congenital cataract was developed secondarily in these patients and provided a clue for the early diagnosis of metabolic disorders like homocystinuria to prevent further complications and morbidity.

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Congenital cataract: An ocular manifestation of classical homocystinuria

Cited by 6 publications

References 19 publications

Methylation-associated pathways in Macular Telangiectasia Type 2 and ophthalmologic findings in patients with genetic methylation disorders

Methylation-associated pathways in Macular Telangiectasia Type 2 and ophthalmologic findings in patients with genetic methylation disorders

Association of selected genetic variants in CBS and MTHFR genes in a cohort of children with homocystinuria in Sri Lanka

Congenital cataract: An ocular manifestation of classical homocystinuria

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