Recessive variants in COL25A1 gene as novel cause of arthrogryposis multiplex congenita with ocular congenital cranial dysinnervation disorder
Por:
Natera-de Benito D, Jurgens JA, Yeung A, Zaharieva IT, Manzur A, DiTroia SP, Di Gioia SA, Pais L, Pini V, Barry BJ, Chan WM, Elder JE, Christodoulou J, Hay E, England EM, Munot P, Hunter DG, Feng L, Ledoux D, O'Donnell-Luria A, Phadke R, Engle EC, Sarkozy A and Muntoni F
Publicada:
1 abr 2022
Ahead of Print:
1 feb 2022
Resumen:
A proper interaction between muscle-derived collagen XXV and its motor neuron-derived receptors protein tyrosine phosphatases sigma and delta (PTP sigma/delta) is indispensable for intramuscular motor innervation. Despite this, thus far, pathogenic recessive variants in the COL25A1 gene had only been detected in a few patients with isolated ocular congenital cranial dysinnervation disorders. Here we describe five patients from three unrelated families with recessive missense and splice site COL25A1 variants presenting with a recognizable phenotype characterized by arthrogryposis multiplex congenita with or without an ocular congenital cranial dysinnervation disorder phenotype. The clinical features of the older patients remained stable over time, without central nervous system involvement. This study extends the phenotypic and genotypic spectrum of COL25A1 related conditions, and further adds to our knowledge of the complex process of intramuscular motor innervation. Our observations indicate a role for collagen XXV in regulating the appropriate innervation not only of extraocular muscles, but also of bulbar, axial, and limb muscles in the human.
Filiaciones:
Natera-de Benito D:
Dubowitz Neuromuscular Centre, UCL Great Ormond Street Hospital, Institute of Child Health, London, UK
Neuromuscular Unit, Department of Neurology, Hospital Sant Joan de Déu, Barcelona, Spain
Jurgens JA:
Program in Medical and Population Genetics and Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142
Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA
Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA
Yeung A:
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Parkville, Victoria, 3052, Australia
Department of Paediatrics, University of Melbourne, Parkville, Victoria, 3052, Australia
Zaharieva IT:
Dubowitz Neuromuscular Centre, UCL Great Ormond Street Hospital, Institute of Child Health, London, UK
Manzur A:
Dubowitz Neuromuscular Centre, UCL Great Ormond Street Hospital, Institute of Child Health, London, UK
DiTroia SP:
Program in Medical and Population Genetics and Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142
Di Gioia SA:
Program in Medical and Population Genetics and Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142
Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA
Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA
Pais L:
Program in Medical and Population Genetics and Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142
Pini V:
Dubowitz Neuromuscular Centre, UCL Great Ormond Street Hospital, Institute of Child Health, London, UK
Barry BJ:
Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA
Howard Hughes Medical Institute, Chevy Chase, MD, USA
Chan WM:
Program in Medical and Population Genetics and Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142
Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA
Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA
Howard Hughes Medical Institute, Chevy Chase, MD, USA
Elder JE:
Department of Paediatrics, University of Melbourne, Parkville, Victoria, 3052, Australia
Department of Ophthalmology, Royal Childrens's Hospital, Parkville, Victoria, 3052, Australia
Christodoulou J:
Murdoch Children's Research Institute, Melbourne, VIC, 3052, Australia
Department of Paediatrics, University of Melbourne, Melbourne, VIC, 3052, Australia
Hay E:
Department of Clinical Genetics, North East Thames Regional Genetic Service, Great Ormond Street Hospital, London, UK
England EM:
Program in Medical and Population Genetics and Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142
Munot P:
Dubowitz Neuromuscular Centre, UCL Great Ormond Street Hospital, Institute of Child Health, London, UK
Hunter DG:
Department of Ophthalmology, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA
Feng L:
Dubowitz Neuromuscular Centre, UCL Great Ormond Street Hospital, Institute of Child Health, London, UK
Ledoux D:
Department of Ophthalmology, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA
O'Donnell-Luria A:
Program in Medical and Population Genetics and Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142
Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA
Phadke R:
Dubowitz Neuromuscular Centre, UCL Great Ormond Street Hospital, Institute of Child Health, London, UK
Engle EC:
Program in Medical and Population Genetics and Center for Mendelian Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, 02142
Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA
Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA
Howard Hughes Medical Institute, Chevy Chase, MD, USA
Department of Ophthalmology, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA
Sarkozy A:
Dubowitz Neuromuscular Centre, UCL Great Ormond Street Hospital, Institute of Child Health, London, UK
Muntoni F:
Dubowitz Neuromuscular Centre, UCL Great Ormond Street Hospital, Institute of Child Health, London, UK
Centre for Neuromuscular Diseases, UCL Institute of Neurology, London, WC1N 3BG, UK
NIHR Great Ormond Street Hospital Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
Green Submitted
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