Novel variant of COL12A1 gene causing neonatal hypotonia and respiratory failure

The COL12A1 gene encodes Collagen XII α 1 chain, forming a biologically functional Collagen XII through a trimeric structure. Collagen XII dysfunction can lead to hereditary neuromuscular diseases with phenotypic profiles ranging from rare Ullrich congenital muscular dystrophy 2 (biallelic variant) to Bethlem myopathy 2 (uniallelic variant). Currently, only 29 COL12A1 deficiency cases have been reported, mainly featuring hypotonia, progressive muscular dystrophy, and skeletal deformities. Newborns cases were relatively rare. Here, we describe a neonate with hypotonia, weak spontaneous movement, convulsions, and respiratory failure at birth. Identification of a novel variant of COL12A1 by whole exome sequencing and Sanger sequencing, NM_004370.6: c.7622 C > T, p.Ser2541Phe. Molecular dynamics simulation revealed its location in the thrombospondin N-terminal domain, potentially destabilizing the Collagen XII trimer's structure. Our case report expands the COL12A1 genotype and phenotype spectrum, suggesting the presence of neonatal hypotonia and highlighting the importance of vigilance for respiratory clinical manifestations.