Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary spherocytosis (HS) is the most common inherited hemolytic anemia characterized by the presence of spherical-shaped erythrocytes on the peripheral blood smear, hemolysis, splenomegaly, jaundice, and gallstones. To date, mutations in at least five genes (ANK1, EPB42, SLC4A1, SPTA1, and SPTB) have been found to be associated with different subtypes of HS. Here, we aim to investigate the presence of novel as well as known mutations in 35 Chinese patients with clinically suspected HS. Whole-exome sequencing (WES) has identified 3 patients with SLC4A1, 16 patients with ANK1, and 16 patients with SPTB mutations, including 5 splicing, 12 nonsense, 9 frameshift, 7 missense, and 1 start-loss mutation, indicating that SPTB and ANK1 are the most frequently mutated genes in Chinese HS patients. Among 34 mutations identified, 21 were novel. Most of SPTB and ANK1 mutations were nonsense (8/16) and frameshift (6/16) mutations. By trio analysis of eight families we have confirmed six de novo mutations. In addition, genotype-phenotype analysis was also performed by comparing clinical manifestations among three groups of patients with SPTB, ANK1, and SLC4A1 mutations. It revealed that patients with ANK1 mutations had a significantly higher level of MCV and MCH but lower percentage of spherocytes compared with those carrying SPTB mutations. In conclusion, our results suggested that molecular diagnosis by next-generation sequencing (NGS) is a fast, economic, and accurate way to detect and identify pathogenic alterations of inherited diseases, highlighting the potential usage of NGS in clinical practice.
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PMID:Identification of new mutations in patients with hereditary spherocytosis by next-generation sequencing. 3198 Jul 36

Hereditary spherocytosis (HS) is an inherited disorder characterized by anemia, splenomegaly, and spherical-shaped erythrocytes, caused by mutations in erythrocyte membrane Protein Genes (ANK1, SPTB, SLC4A1, SPTA1, and EPB42). We investigated molecular spectrum and genotype-phenotype correlation in HS patients in Hubei province, central China. Twenty-three patients with HS were included. A next-generation sequencing (NGS) panel targeting ANK1, SPTB, SLC4A1, SPTA1, and EPB42 genes was used to screen potential variants. Sanger sequencing was applied to validate variants. Of the twenty-three patients, thirteen patients carried ANK1 variants, and ten patients harbored SPTB variants, including ten non-sense, six indel, four splice site, one start-loss, and one missense variant. Four out of twenty-two variants in our study were known, and eighteen variants were novel. Most ANK1 and SPTB variants were indel (5/12) or non-sense (7/10), respectively. Family member analysis in thirteen families showed that six variants were de novo. Variable expressivities were observed in a pair of twins with ANK1 c.341C > T variant, and two unrelated patients both carried ANK1 c.2T > A variant. Genotype-phenotype analysis found no significant difference between ANK1 and SPTB regarding the levels of Hb, RBC, MCV, MCH, and MCHC. However, variants in the ANK1 death domain were associated with lower levels of MCV and MCH compared to other ANK1 domains. In conclusion, NGS is a fast way to provide a molecular HS diagnosis. We also identified unique genetic and clinical characteristics of patients with HS in Hubei Province, China. However, a large sample size is needed to further investigate the genotype-phenotype correlation.
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PMID:Genetic and Clinical Characteristics of Patients With Hereditary Spherocytosis in Hubei Province of China. 3301 18