A de novo ANK1 mutation associated to hereditary spherocytosis: a case report

Abstract

Background Hereditary spherocytosis (HS) is a type of hemolytic anemia caused by abnormal red cell membrane skeletal proteins with few unique clinical manifestations in the neonate and infant. An ANK1 gene mutation is the most common cause of HS. Case presentation The patient was a 11-month-old boy who suffered from anemia and needed a regular transfusion therapy at an interval of 2–3 months. Hematological investigations showed moderate anemia (Hb80 g/L). Red cells displayed microcytosis (MCV76.4 fl, MCH25.6 pg, MCHC335 g/L). The reticulocytes were elevated (4.8%) and the spherocytes were increased (10%). Direct antiglobulin test was negative. Biochemical test indicated a slight elevation of bilirubin, mainly indirect reacting (TBIL32.5 μmol/L, IBIL24 μmol/L). The neonatal HS ratio is 4.38, obviously up the threshold. Meanwhile, a de novo ANK1 mutation (exon 25:c.2693dupC:p.A899Sfs*11) was identified by next-generation sequencing (NGS). Thus, hereditary spherocytosis was finally diagnosed. Conclusions Gene detection should be considered in some hemolytic anemia which is difficult to diagnose by routine means. We identified a novel de novo ANK1 heterozygous frameshift mutation in a Yi nationality patient while neither of his parents carried this mutation. Electronic supplementary material The online version of this article (10.1186/s12887-019-1436-4) contains supplementary material, which is available to authorized users.

Gastrulation-stage gene expression inNipbl+/-mouse embryos foreshadows the development of syndromic birth defects

“…The copyright holder for this preprint this version posted October 17, 2023. ; https://doi.org/10.1101/2023.10.16.558465 doi: bioRxiv preprint but also several genes connected to the Wnt signaling pathway, such as Ror2, Ptk7, and Fzd2 (87)(88)(89). In parallel, a pronounced underexpression was observed in numerous hemoglobin genes (Hbb-bh1, Hbb-y, Hba-x, and Hba-a1) as well as genes encoding definitive erythrocyte proteins, including Gypa, Spta1, Ank1, and Sptb (90)(91)(92)(93). This pattern of underexpressed genes was strongly mirrored in the germ layers of CC-stage Nipbl +/embryos.…”

Clinical manifestations of 17 Chinese children with hereditary spherocytosis caused by novel mutations of the ANK1 gene and phenotypic analysis

“…After reviewing all available published reports of Chinese HS patients carrying ANK1 mutations, a total of 129 reported and 15 unreported ANK1 variants were further summarized, including missense ( n = 19), frameshift ( n = 40), non-sense ( n = 46), and splicing ( n = 21) variants ( Supplementary Table S3 ) ( Huang et al, 2019 ; Bin et al, 2020 ; Chai et al, 2020 ; Wang et al, 2020 ; Zhu et al, 2020 ; Wang et al, 2021a ; Wu et al, 2021a ; Xie et al, 2021a ; Wang et al, 2021b ; Xie et al, 2021b ; Wang et al, 2021c ; Fu et al, 2022 ; Li et al, 2022 ; Xiang and Shen, 2022 ; Zhao et al, 2022 ; Xu et al, 2023 ; Zhu et al, 2023 ). When we extended the Hb and T-Bil data to all 144 probands, the difference in Hb between regulatory domains and membrane binding domains disappeared ( Figure 5C ).…”

De novo variations of ANK1 gene caused hereditary spherocytosis in two Chinese children by affecting pre-mRNA splicing

“…In both patients, a low percentage of spherical red blood cells was shown in peripheral blood smears. Additionally, the parents of the patients carrying de novo mutations had normal clinical characteristics and haematological test results [ 15 , 16 ]. Comprehensive clinical and genetic analyses were performed to provide detailed characteristics of the patients’ genotypes and phenotypes.…”