Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis

Wang, Rongrong; Yang, Shuanghao; Xu, Ming; Huang, Jia; Liu, Hongyan; Gu, Weiyue; Zhang, Xue

doi:10.1007/s11427-017-9232-6

Cited by 50 publications

(52 citation statements)

References 36 publications

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“…All identified variants (21, among which 13 novel) were classified as likely pathogenic or pathogenic loss-of-function mutations. A recent exomic study of 38 Chinese patients with suspected HS found mutations of ANK1 or SPTB in all patients [24]. Gallagher et al in 2019 [25] reported on a group of 24 recessive HS patients explored by WES and whole genome sequencing (WGS), all having mutations found in SPTA1.…”

Section: Discussionmentioning

confidence: 99%

Exome sequencing for diagnosis of congenital hemolytic anemia

Mansour‐Hendili

Aissat

Badaoui

et al. 2020

Preprint

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Background: Congenital hemolytic anemia constitutes a heterogeneous group of rare genetic disorders of red blood cells. Diagnosis is based on clinical data, family history and phenotypic testing, genetic analyses being usually performed as a late step. In this study, we explored 40 patients with congenital hemolytic anemia by whole exome sequencing: 20 patients with hereditary spherocytosis and 20 patients with unexplained hemolysis. Results: A probable genetic cause of disease was identified in 82.5% of the patients (33/40): 100% of those with suspected hereditary spherocytosis (20/20) and 65% of those with unexplained hemolysis (13/20). We found that several patients carried genetic variations in more than one gene (3/20 in the hereditary spherocytosis group, 6/13 fully elucidated patients in the unexplained hemolysis group), giving a more accurate picture of the genetic complexity of congenital hemolytic anemia. In addition, whole exome sequencing allowed us to identify genetic variants in non-congenital hemolytic anemia genes that explained part of the phenotype in 3 patients. Conclusion: The rapid development of next generation sequencing has rendered the genetic study of these diseases much easier and cheaper. Whole exome sequencing in congenital hemolytic anemia could provide a more precise and quicker diagnosis, improve patients’ healthcare and probably has to be democratized notably for complex cases. .

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Section: Discussionmentioning

confidence: 99%

Exome sequencing for diagnosis of congenital hemolytic anemia

Mansour‐Hendili

Aissat

Badaoui

et al. 2020

Preprint

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“…Hereditary spherocytosis (HS), one of the most common monogenic haemolytic anaemia diseases, is characterized by spherical‐shaped erythrocytes in the peripheral blood of patients. Hereditary spherocytosis is prevalent worldwide, especially in the Northern European population, with an incidence rate of 1:2000 . To date, no exact epidemiological data related to HS in China are available, and the estimated prevalence is 1.27/100 000 in males and 1.49/100 000 in females, which was reported by Wang et al only …”

Section: Introductionmentioning

confidence: 92%

Two novel ANK1 loss‐of‐function mutations in Chinese families with hereditary spherocytosis

Hao

et al. 2019

J Cellular Molecular Medi

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Hereditary spherocytosis (HS) is the most common inherited haemolytic anaemia disorder. ANK1 mutations account for most HS cases, but pathogenicity analysis and functional research have not been widely performed for these mutations. In this study, in order to confirm diagnosis, gene mutation was screened in two unrelated Chinese families with HS by a next‐generation sequencing (NGS) panel and then confirmed by Sanger sequencing. Two novel heterozygous mutations (c.C841T, p.R281X and c.T290G, p.L97R) of the ANK1 gene were identified in the two families respectively. Then, the pathogenicity of the two new mutations and two previously reported ANK1 mutations (c.C648G, p.Y216X and c.G424T, p.E142X) were studied by in vitro experiments. The four mutations increased the osmotic fragility of cells, reduced the stabilities of ANK1 proteins and prevented the protein from localizing to the plasma membrane and interacting with SPTB and SLC4A1. We classified these four mutations into disease‐causing mutations for HS. Thus, conducting the same mutation test and providing genetic counselling for the two families were meaningful and significant. Moreover, the identification of two novel mutations enriches the ANK1 mutation database, especially in China.

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“…Moreover, a molecular diagnosis is essential when the clinical diagnosis is not certain, for example in patients that require frequent transfusions. Genetic testing for RBC defects is moving increasingly towards customised multi‐gene panels (i.e., targeted‐NGS) and whole‐exome sequencing (Roy et al , ; Russo et al , ; Wang et al , ). The diagnostic yield of targeted‐NGS approach ranges between 40% and 65% of screened patients, depending on the number of genes included in each panel (Roy et al , ; Russo et al , ).…”

Section: New Insights Into the Diagnosis Of Red Cell Membrane Disordersmentioning

confidence: 99%

Advances in understanding the pathogenesis of red cell membrane disorders

2019

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Summary Hereditary erythrocyte membrane disorders are caused by mutations in genes encoding various transmembrane or cytoskeletal proteins of red blood cells. The main consequences of these genetic alterations are decreased cell deformability and shortened erythrocyte survival. Red blood cell membrane defects encompass a heterogeneous group of haemolytic anaemias caused by either (i) altered membrane structural organisation (hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis and Southeast Asian ovalocytosis) or (ii) altered membrane transport function (overhydrated hereditary stomatocytosis, dehydrated hereditary stomatocytosis or xerocytosis, familial pseudohyperkalaemia and cryohydrocytosis). Herein we provide a comprehensive review of the recent literature on the molecular genetics of erythrocyte membrane defects and their reported clinical consequences. We also describe the effect of low‐expression genetic variants on the high inter‐ and intra‐familial phenotype variability of erythrocyte structural defects.

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Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis

Cited by 50 publications

References 36 publications

Exome sequencing for diagnosis of congenital hemolytic anemia

Exome sequencing for diagnosis of congenital hemolytic anemia

Two novel ANK1 loss‐of‐function mutations in Chinese families with hereditary spherocytosis

Advances in understanding the pathogenesis of red cell membrane disorders

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