ArticleHuman molecular genetics2018
Visual impairment and progressive phthisis bulbi caused by recessive pathogenic variant in MARK3.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 25 citations in OpenAlex.
- Deciphering the Genetic Basis of Degenerative and Developmental Eye Disorders in 50 Pakistani Consanguineous Families Using Whole-Exome Sequencing.International journal of molecular sciences · 2025Article
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- Microtubule-affinity regulating kinase family members distinctively affect tau phosphorylation and promote its toxicity in a Drosophila model.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- Integrating non-mammalian model organisms in the diagnosis of rare genetic diseases in humans.Nature reviews. Genetics · 2024Review
- FOXI3 pathogenic variants cause one form of craniofacial microsomia.Nature communications · 2023Article
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- Variants in CAPZA2, a member of an F-actin capping complex, cause intellectual disability and developmental delay.Human molecular genetics · 2020Article
- Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms.Neuron · 2020Article
- The fruit fly at the interface of diagnosis and pathogenic mechanisms of rare and common human diseases.Human molecular genetics · 2019Article
- Bi-allelic Variants in IQSEC1 Cause Intellectual Disability, Developmental Delay, and Short Stature.American journal of human genetics · 2019Article
- Carrier screening for recessive disorders.Nature reviews. Genetics · 2019Review
- In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila.Journal of visualized experiments : JoVE · 2019Article
- Bi-allelic Variants in DYNC1I2 Cause Syndromic Microcephaly with Intellectual Disability, Cerebral Malformations, and Dysmorphic Facial Features.American journal of human genetics · 2019Article
- Biallelic variants in FBXL3 cause intellectual disability, delayed motor development and short stature.Human molecular genetics · 2019Article
- Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts.American journal of human genetics · 2018Article
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Developmental eye defects often severely reduce vision. Despite extensive efforts, for a substantial fraction of these cases the molecular causes are unknown. Recessive eye disorders are frequent in consanguineous populations and such large families with multiple affected individuals provide an opportunity to identify recessive causative genes. We studied a Pakistani consanguineous family with three affected individuals with congenital vision loss and progressive eye degeneration. The family was analyzed by exome sequencing of one affected individual and genotyping of all family members. We have identified a non-synonymous homozygous variant (NM_001128918.2: c.1708C > G: p.Arg570Gly) in the MARK3 gene as the likely cause of the phenotype. Given that MARK3 is highly conserved in flies (I: 55%; S: 67%) we knocked down the MARK3 homologue, par-1, in the eye during development. This leads to a significant reduction in eye size, a severe loss of photoreceptors and loss of vision based on electroretinogram (ERG) recordings. Expression of the par-1 p.Arg792Gly mutation (equivalent to the MARK3 variant found in patients) in developing fly eyes also induces loss of eye tissue and reduces the ERG signals. The data in flies and human indicate that the MARK3 variant corresponds to a loss of function. We conclude that the identified mutation in MARK3 establishes a new gene-disease link, since it likely causes structural abnormalities during eye development and visual impairment in humans, and that the function of MARK3/par-1 is evolutionarily conserved in eye development.
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