ObjectiveTo investigate clinical characteristics and related gene mutations of hereditary spherocytosis (HS).
MethodsFrom January 1, 2017 and July 31, 2019, ten cases of children diagnosed with HS in outpatients and inpatients at Kunming Children′s Hospital were selected as study subjects. Among them, 3 cases were female and 7 cases were male, with an average age of 4.5 years. General clinical data of children with HS were collected, and high-throughput sequencing technology was used to detect related gene mutations in the children. Clinical data, related gene mutations and treatment efficacy of HS children were analyzed retrospectively. The procedure of this study is accordance with the requirement of theWorld Medical Association Declaration of Helsinkirevised in 2013.
Results① Clinical manifestations of anemia, jaundice and spleen were significant in all 10 cases of HS children. Anemia was mainly small-cell anemia, with 4 cases of severe anemia, 4 cases of moderate anemia and 2 cases of mild anemia. Splenomegaly of the children was mainly mild and moderate, with 4 cases of mild splenomegaly, 6 cases of moderate splenomegaly, and none of them had severe splenomegaly. Transfusion frequency of the children varied. Among them, the proportion of spherical erythrocytes in peripheral blood increased in 3 cases, 7 cases were normal. Four cases were increased in osmotic brittleness, and 6 cases were normal. Thalassemia genes of children were normal. Levels of ferritin and red blood cell glucose-6-phosphate dehydrogenase (G-6-PD) of children were normal. ② High throughput gene sequencing results showed, among the 10 children, 6 cases had ANK1 gene mutation, 2 cases had SPTA1 gene mutation, 1 case had SPTB gene mutation, and 1 case had SPTB gene exon 2-3 suspected duplication. Among them, ANK1 gene c. 4585C>T (p.R1529X) and c. 3877C>T (p.R1293X) mutations were reported to be associated with spherocytosis in Human Gene Mutation Database (HGMD) professional version. ANK1 genes c. 1471C>T (p.Q491X), c. 1817delT (p.L606Cfs*31), c. 4390+ 5G>T (IVS36dsG-T+ 5), c. 4189C>T (p.L1397F) mutations were not reported in the HGMD professional version. According to American College of Medical Genetics and Genomics (ACMG) guidelines, ANK1 gene c. 1471C>T (p.Q491X) and c. 1817delT (p.L606Cfs*31) mutations were considered as new suspected pathogenic mutations. SPTA1 gene c. 4766G>A (p.W1589X), c. 5432G>A (p.R1811Q) mutation, SPTB gene exon 2-3 suspected duplication were not reported in literature. Among them, SPTA1 gene c. 4766G>A (p.R1811Q) mutation was considered as a new suspected pathogenic mutation. SPTB gene c. 4735C>T (p.R1579X) mutation was reported in the HGMD professional version. SPTB gene c. 797_798del (p.I266Nfs*28) mutation was not reported in the literature and was considered to be a new suspected pathogenic mutation. ③ In this study, among the 4 cases who received splenic artery embolization, 2 cases did not receive blood transfusion after surgery. Within 6 months after splenic artery embolization, 1 case did not receive blood transfusion. And after 6 months, this case received blood transfusion once every 2-3 months. One child was lost during follow-up. Among the rest 6 children who did not receive splenic artery embolization, 1 case received blood transfusion once every 2 months, 5 case with hemoglobin (Hb) value over 90 g/L.
ConclusionsHigh-throughput sequencing technology can help diagnose HS with atypical clinical features. In this study, 4 unreported gene mutations of ANK1, SPTA and SPTB genes were found.
