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A decade has passed since transmembrane coiled-coil domains 1 (TMCO1) defect syndrome was identified in 11 undiagnosed patients within the Old Order Amish of Northeastern Ohio-a disorder characterized by a distinctive craniofacial dysmorphism, skeletal anomalies and global developmental delay. Twenty seven patients, from diverse ethnic groups, have been reported with pathogenic TMCO1 variants now recognized to cause cerebrofaciothoracic dysplasia (CFTD). The implication of previously uncharacterized TMCO1 within disease has instigated a 10-year journey to understand the function of TMCO1 protein in Ca 2+ homeostasis. TMCO1 is an ER Ca 2+ leak channel which facilitates Ca 2+ leak upon ER "overload" through the novel Ca 2+ load activated Ca 2+ mechanism. This mini-review brings together the clinical and scientific advances made since the discovery of TMCO1 deficiency in disease, including broadened phenotype, understanding of pathophysiology, and implications to patient management of TMCO1 defect syndrome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Batchelor-Regan, Xin, Zhou and Wang.)

To investigate the association of known candidate genes with the visual field (VF) progression of primary open angle glaucoma (POAG) in a Han Chinese population. We included 440 POAG patients in this study. Fourteen previously reported single nucleotide polymorphisms (SNPs) at five different gene regions ( TGFBR3-CDC7 , TMCO1 , CDKN2B-AS1 , ATOH7 , and SIX1/SIX6 ) were genotyped. Age at diagnosis, gender, intraocular pressure (IOP), mean defect (MD) of VF, vertical cup disk ratio (VCDR), best corrected visual acuity (BCVA), central corneal thickness (CCT), and axial length (AL) were recorded at baseline. Patients were followed up for 5 years to evaluate VF progression over time. Clinical information and allele frequencies of 14 SNPs were compared between patients who progressed and who did not within 5 years by multivariate logistic regression. Survival analysis was performed to evaluate the contribution of the associated SNP by cox regression. Greater MD ( P < 0.0001), increased VCDR ( P = 0.0001), higher IOP ( P = 0.0003), worse BCVA ( P = 0.002), and older age ( P = 0.030) at the baseline were associated with VF progression. Both multivariate logistic regression and cox regression survival analysis showed none of the 14 SNPs statistically associated with VF progression adjusted with age at diagnosis, gender, baseline MD, follow-up IOP, CCT, and AL. There were lack of association of SNPs at TGFBR3-CDC7 , TMCO1 , ATOH7 , CDKN2B-AS1 , SIX1/SIX6 loci with VF progression in POAG patients in Han Chinese. Further studies are needed to evaluate the association of genetic variants with VF progression.