Abstract
Hereditary spherocytosis (HS), the most common cause of congenital hemolytic anemia, is caused by deficiency of the erythrocyte membrane proteins. Five causative genes (ANK1, SPTB, SPTA1, SLC4A1, and EPB42) have been identified. To date, molecular genetic studies have been performed in different populations, including the American, European, Brazilian, Japanese and Korean populations, whereas only a few studies have been described in the Chinese population. Here, by reanalysis of the exome data, we revealed causative mutations and established a definitive diagnosis of HS in all 38 Chinese families. We found 34 novel mutations and four reported mutations in three known HS-causing genes—17 in ANK1, 17 in SPTB and four in SLC4A1, suggesting that ANK1 and SPTB are the major genes in Chinese patients with HS. All of the ANK1 or SPTB mutations, scattered throughout the entire genes, are non-recurrent; and most of them are null mutations, which might cause HS via a haploinsufficiency mechanism. De novo mutations in ANK1 or SPTB often occur with an unexpected high frequency (87.5% and 64.2%, respectively). Our study updates our knowledge about the genetic profile of HS in Chinese and shows that family-based, especially parent-offspring trio, sequencing analysis can help to increase the diagnostic power and improve diagnostic efficiency.
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Acknowledgements
We thank all the individuals for their participation in this study. This work was supported by the National Key Research and Development Program of China (2016YFC0905100), the CAMS Innovation Fund for Medical Sciences (2016-I2M-1-002), the National Natural Science Foundation of China (NSFC) (81230015), the Beijing Municipal Science and Technology Commission (Z151100003915078), the Medical Science and Technology Research Projects of Henan Provincial Health Bureau (201601019) and the Scientific and Technological Projects of the Technology Bureau of Henan Provincial Technology (172102410010).
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Wang, R., Yang, S., Xu, M. et al. Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis. Sci. China Life Sci. 61, 947–953 (2018). https://doi.org/10.1007/s11427-017-9232-6
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DOI: https://doi.org/10.1007/s11427-017-9232-6