@article {1629472, title = {Recessive variants in COL25A1 gene as novel cause of arthrogryposis multiplex congenita with ocular congenital cranial dysinnervation disorder}, journal = {Hum Mutat}, volume = {43}, number = {4}, year = {2022}, month = {2022 Apr}, pages = {487-498}, abstract = {A proper interaction between muscle-derived collagen XXV and its motor neuron-derived receptors protein tyrosine phosphatases σ and δ (PTP σ/δ) 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.}, keywords = {Arthrogryposis, Face, Humans, Muscle, Skeletal, Mutation, Phenotype}, issn = {1098-1004}, doi = {10.1002/humu.24333}, author = {Natera-de Benito, Daniel and Jurgens, Julie A and Yeung, Alison and Zaharieva, Irina T and Manzur, Adnan and DiTroia, Stephanie P and Di Gioia, Silvio Alessandro and Pais, Lynn and Pini, Veronica and Barry, Brenda J and Chan, Wai-Man and Elder, James E and Christodoulou, John and Hay, Eleanor and England, Eleina M and Munot, Pinki and Hunter, David G and Feng, Lucy and Ledoux, Danielle and O{\textquoteright}Donnell-Luria, Anne and Phadke, Rahul and Engle, Elizabeth C and Sarkozy, Anna and Muntoni, Francesco} }