ArticleAmerican journal of human genetics2017
Large Intragenic Deletion in DSTYK Underlies Autosomal-Recessive Complicated Spastic Paraparesis, SPG23.
Article in American journal of human genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- Mouse and human studies support DSTYK loss of function as a low-penetrance and variable expressivity risk factor for congenital urinary tract anomalies.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- Copy Number Variations in Hereditary Spastic Paraplegia-Related Genes: Evaluation of an Iranian Hereditary Spastic Paraplegia Cohort and Literature Review.Molecular syndromology · 2023Article
- Functions of the RIP kinase family members in the skin.Cellular and molecular life sciences : CMLS · 2023Review
- DSTYK inhibition increases the sensitivity of lung cancer cells to T cell-mediated cytotoxicity.The Journal of experimental medicine · 2022Article
- Hereditary Spastic Paraplegia: An Update.International journal of molecular sciences · 2022Review
- Article
- Exome sequencing implicates a novel heterozygous missense variant in DSTYK in autosomal dominant lower urinary tract dysfunction and mild hereditary spastic paraparesis.Molecular and cellular pediatrics · 2021Article
- Importance of lipids for upper motor neuron health and disease.Seminars in cell & developmental biology · 2021Review
- Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview.Frontiers in molecular biosciences · 2021Review
- Exploring the possibility of predicting human head hair greying from DNA using whole-exome and targeted NGS data.BMC genomics · 2020Article
- Article
- Dstyk mutation leads to congenital scoliosis-like vertebral malformations in zebrafish via dysregulated mTORC1/TFEB pathway.Nature communications · 2020Article
- DSTYK Promotes Metastasis and ChemoresistanceFrontiers in pharmacology · 2020Article
- A DSTYK mutation activates ERK1/2 signaling to promote intraspinal dissemination in a case of solitary fibrous tumor/hemangiopericytoma.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- Evolutionary and functional impact of common polymorphic inversions in the human genome.Nature communications · 2019Article
- NGS Technologies as a Turning Point in Rare Disease Research , Diagnosis and Treatment.Current medicinal chemistry · 2018Review
- Genetic basis of human congenital anomalies of the kidney and urinary tract.The Journal of clinical investigation · 2018Review
- Perspectives on the Genomics of HSP Beyond Mendelian Inheritance.Frontiers in neurology · 2018Review
Corrections and comments
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Authors and funding
26 authors at 13 institutions in 6 countries.
Funding
Abstract
SPG23 is an autosomal-recessive neurodegenerative subtype of lower limb spastic paraparesis with additional diffuse skin and hair dyspigmentation at birth followed by further patchy pigment loss during childhood. Previously, genome-wide linkage in an Arab-Israeli pedigree mapped the gene to an approximately 25 cM locus on chromosome 1q24-q32. By using whole-exome sequencing in a further Palestinian-Jordanian SPG23 pedigree, we identified a complex homozygous 4-kb deletion/20-bp insertion in DSTYK (dual serine-threonine and tyrosine protein kinase) in all four affected family members. DSTYK is located within the established linkage region and we also found the same mutation in the previously reported pedigree and another Israeli pedigree (total of ten affected individuals from three different families). The mutation removes the last two exons and part of the 3' UTR of DSTYK. Skin biopsies revealed reduced DSTYK protein levels along with focal loss of melanocytes. Ultrastructurally, swollen mitochondria and cytoplasmic vacuoles were also noted in remaining melanocytes and some keratinocytes and fibroblasts. Cultured keratinocytes and fibroblasts from an affected individual, as well as knockdown of Dstyk in mouse melanocytes, keratinocytes, and fibroblasts, were associated with increased cell death after ultraviolet irradiation. Keratinocytes from an affected individual showed loss of kinase activity upon stimulation with fibroblast growth factor. Previously, dominant mutations in DSTYK were implicated in congenital urological developmental disorders, but our study identifies different phenotypic consequences for a recurrent autosomal-recessive deletion mutation in revealing the genetic basis of SPG23.
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