Title |
Yunis-Varón syndrome caused by biallelic VAC14 mutations
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Published in |
European Journal of Human Genetics, June 2017
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DOI | 10.1038/ejhg.2017.99 |
Pubmed ID | |
Authors |
Matthew A Lines, Yoko Ito, Kristin D Kernohan, Wendy Mears, Julie Hurteau-Miller, Sunita Venkateswaran, Leanne Ward, Karine Khatchadourian, Jeff McClintock, Priya Bhola, Philippe M Campeau, Kym M Boycott, Jean Michaud, André BP van Kuilenburg, Sacha Ferdinandusse, David A Dyment |
Abstract |
Yunis-Varón syndrome (YVS) is an autosomal recessive disorder comprising skeletal anomalies, dysmorphism, global developmental delay and intracytoplasmic vacuolation in brain and other tissues. All hitherto-reported pathogenic variants affect FIG4, a lipid phosphatase involved in phosphatidylinositol (3,5)-bisphosphate [PtdIns(3,5)P2] metabolism. FIG4 interacts with PIKfyve, a lipid kinase, via the adapter protein VAC14; all subunits of the resulting complex are essential for PtdIns(3,5)P2 synthesis in the endolysosomal membrane compartment. Here, we present the case of a female neonate with clinical features of YVS and normal FIG4 sequencing; exome sequencing identified biallelic rare coding variants in VAC14. Cultured patient fibroblasts exhibited a YVS-like vacuolation phenotype ameliorated in a dose-dependent fashion by ML-SA1, a pharmacological activator of the lysosomal PtdIns(3,5)P2 effector TRPML1. The patient developed a diffuse leukoencephalopathy with loss of the normal N-acetylaspartate spectrographic peak and presence of a large abnormal peak consistent with myoinositol. We report that VAC14 is a second gene for Yunis-Varón syndrome.European Journal of Human Genetics advance online publication, 21 June 2017; doi:10.1038/ejhg.2017.99. |
X Demographics
Geographical breakdown
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Switzerland | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 38 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 7 | 18% |
Student > Bachelor | 4 | 11% |
Researcher | 3 | 8% |
Professor | 3 | 8% |
Student > Doctoral Student | 2 | 5% |
Other | 5 | 13% |
Unknown | 14 | 37% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 9 | 24% |
Medicine and Dentistry | 7 | 18% |
Agricultural and Biological Sciences | 2 | 5% |
Neuroscience | 2 | 5% |
Environmental Science | 1 | 3% |
Other | 1 | 3% |
Unknown | 16 | 42% |