Novel PMM2 missense mutation in a Chinese family with non-syndromic premature ovarian insufficiency

Tianliu Peng; Chao Lv; Hangjing Tan; Jiafeng Huang; Hailun He; Yan Wang; Minghua Zeng; Dajing Yi; Jie Li; Hongwen Deng; Xiaobo Shi; Hongmei Xiao

doi:10.1007/s10815-019-01675-8

Novel PMM2 missense mutation in a Chinese family with non-syndromic premature ovarian insufficiency

J Assist Reprod Genet. 2020 Feb;37(2):443-450. doi: 10.1007/s10815-019-01675-8. Epub 2020 Jan 4.

Authors

Tianliu Peng^{1

2}, Chao Lv^{1

2}, Hangjing Tan^{1

2}, Jiafeng Huang³, Hailun He³, Yan Wang^{1

2}, Minghua Zeng^{1

2}, Dajing Yi^{1

2}, Jie Li⁴, Hongwen Deng^{2

5}, Xiaobo Shi⁶, Hongmei Xiao^{7

8}

Affiliations

¹ Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410013, China.
² Center for Reproductive Health and Systems Biology and Data information, School of Basic Medical Science, Central South University, Changsha, 410013, Hunan, China.
³ Life of Sciences, Central South University, Changsha, 410013, China.
⁴ Department of Obstetrics and Gynecology, Reproductive Medicine Center, Second Xiangya Hospital of Central South University, Changsha, 410011, China.
⁵ Center for Genomics and Bioinformatics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, 70112, USA.
⁶ Department of Obstetrics and Gynecology, Reproductive Medicine Center, Second Xiangya Hospital of Central South University, Changsha, 410011, China. 747660202@qq.com.
⁷ Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, 410013, China. hmxiao@csu.edu.cn.
⁸ Center for Reproductive Health and Systems Biology and Data information, School of Basic Medical Science, Central South University, Changsha, 410013, Hunan, China. hmxiao@csu.edu.cn.

Abstract

Purpose: This study sought to identify a disease-related gene in a consanguineous Chinese family in which there were two premature ovarian insufficiency (POI) sisters.

Method: We used whole-exome sequencing and Sanger sequencing to identify the disease-causing gene. Results were verified using an assay of mutant protein and in silico analyses.

Result: We identified a novel missense mutation (NM_000303: c.556G>A, p.Gly186Arg) in the PMM2 gene. The two sisters suffer from premature ovarian insufficiency (POI) only and have no other symptoms of congenital disorder of glycosylation type-1a (CDG-Ia). We found that the enzymic activity of the mutant PMM2 protein was reduced by 55.21% (p < 0.05) when compared with wild type, and many in silico tools suggested the mutation is disease-related.

Conclusion: This particular gene modification results in changes in activity of phosphomannomutase modification, which could lead to PMM2-CDG-Ia with an uncommon phenotype.

Keywords: Congenital disorder of glycosylation type-1a (CDG-Ia); Non-syndromic premature ovarian insufficiency; PMM2; Premature ovarian insufficiency (POI).

MeSH terms

Adult
China
Consanguinity
Female
Genetic Predisposition to Disease*
Humans
Mutation, Missense / genetics
Pedigree
Phenotype
Phosphotransferases (Phosphomutases) / genetics*
Primary Ovarian Insufficiency / genetics*
Primary Ovarian Insufficiency / physiopathology
Siblings

Substances

Phosphotransferases (Phosphomutases)
phosphomannomutase 2, human

Abstract

MeSH terms

Substances

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