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

Hum Genomics. 2021 Jul 8;15(1):42. doi: 10.1186/s40246-021-00343-2.

Mahsa Sadat Asl Mohajeri ¹, Atieh Eslahi ¹ ² ³, Zeinab Khazaii ⁴, Mohammad Reza Moradi ¹, Reza Pazhoomand ⁵ ⁶, Shima Farrokhi ¹ ³, Masoumeh Heidari Feizabadi ¹, Farzaneh Alizadeh ¹, Majid Mojarrad ⁷ ⁸ ⁹

Affiliations

1 Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
2 Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
3 Medical Genetics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
4 Genetic Center of Khorasan Razavi, Mashhad, Iran.
5 Legal Medicine Research Center, Legal Medicine Organization of Iran, Tehran, Iran.
6 Genetic Department, Shiraz Fertility Center, Shiraz, Iran.
7 Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. majidmojarrad@gmail.com.
8 Medical Genetics Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. majidmojarrad@gmail.com.
9 Genetic Center of Khorasan Razavi, Mashhad, Iran. majidmojarrad@gmail.com.

PMID: 34238371 DOI: 10.1186/s40246-021-00343-2

Abstract

Introduction: Skeletal 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.

Patient: Fetus 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.

Results: Whole 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.

Conclusion: TMEM263 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.

Keywords

Gene discovery; Novel gene; Skeletal dysplasia; Whole exome sequencing.

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