TMEM263: a novel candidate gene implicated in human autosomal recessive severe lethal skeletal dysplasia

Human Genomics

Farzaneh Alizadeh¹  Mahsa Sadat Asl Mohajeri¹  Mohammad Reza Moradi¹  Masoumeh Heidari Feizabadi¹  Shima Farrokhi²  Majid Mojarrad³  Atieh Eslahi⁴  Zeinab Khazaii⁵  Reza Pazhoomand⁶ 

[1] Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;Medical Genetics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;Medical Genetics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;Genetic Center of Khorasan Razavi, Mashhad, Iran;Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;Medical Genetics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;Genetic Center of Khorasan Razavi, Mashhad, Iran;Legal Medicine Research Center, Legal Medicine Organization of Iran, Tehran, Iran;Genetic Department, Shiraz Fertility Center, Shiraz, Iran;

关键词: Skeletal dysplasia;    Novel gene;    Whole exome sequencing;    Gene discovery;   

DOI  :  10.1186/s40246-021-00343-2

来源: Springer

【 摘 要 】

IntroductionSkeletal dysplasia is a common, clinically and genetically heterogeneous disorder in the human population. An increasing number of different genes are being identified causing this disorder. We used whole exome sequencing (WES) for detection of skeletal dysplasia causing mutation in a fetus affected to severe lethal skeletal dysplasia.PatientFetus was assessed by ultrasonography in second trimester of pregnancy. He suffers from severe rhizomelic dysplasia and also pathologic shortening of ribs. WES was applied to finding of causal mutation. Furthermore, bioinformatics analysis was performed to predict mutation impact.ResultsWhole exome sequencing (WES) identified a homozygous frameshift mutation in the TMEM263 gene in a fetus with severe lethal skeletal dysplasia. Mutations of this gene have been previously identified in dwarf chickens, but this is the first report of involvement of this gene in human skeletal dysplasia. This gene plays a key role in the growth hormone signaling pathway.ConclusionTMEM263 can be considered as a new gene responsible for skeletal dysplasia. Given the complications observed in the affected fetus, the mutation of this gene appears to produce much more intense complications than that found in chickens and is likely to play a more important role in bone development in human.

【 授权许可】

CC BY