Clinical and genetic diagnosis of thirteen Japanese patients with hereditary spherocytosis

Abstract

Hereditary spherocytosis is the most frequent cause of hereditary hemolytic anemia and is classified into five subtypes (SPH1-5) according to OMIM. Because the clinical and laboratory features of patients with SPH1-5 are variable, it is difficult to classify these patients into the five subtypes based only on these features. We performed target capture sequencing in 51 patients with hemolytic anemia associated with/without morphological abnormalities in red blood cells. Thirteen variants were identified in five hereditary spherocytosis-related genes (six in ANK1 [SPH1]; four in SPTB [SPH2]; and one in each of SPTA1 [SPH3], SLC4A1 [SPH4], and EPB42 [SPH5]). Among these variants, seven were novel. The distribution pattern of the variants was different from that reported previously in Japan but similar to those reported in other Asian countries. Comprehensive genomic analysis would be useful and recommended, especially for patients without a detailed family history and those receiving frequent blood transfusions due to chronic hemolytic anemia.

A large family of hereditary spherocytosis and a rare case of hereditary elliptocytosis with a novel SPTA1 mutation underdiagnosed in Taiwan: A case report and literature review

“…The distribution of HS-related variants was also different from that identified in a previous study on Japanese patients with HS. [ 23 ] No epidemiological data for HS in Taiwan has been reported.…”

“…The distribution of HS-related variants was also different from that identified in a previous study on Japanese patients with HS. [23] No epidemiological data for HS in Taiwan has been reported. The true prevalence of HE is unknown because many mildly affected individuals are likely to remain undiagnosed.…”

Variant spectrum of PIEZO1 and KCNN4 in Japanese patients with dehydrated hereditary stomatocytosis

“…In most patients, when possible, we rst performed additional red cell membrane functional examinations, including the acidi ed glycerol hemolysis time (AGLT) test, ow-cytometric osmotic fragility (FCM-OF) test, and eosin-5'-maleimide (EMA) binding test with a negative direct antiglobulin test as per previously reported methods 10 . DHSt was suspected when clinical ndings such as hemolytic anemia with stomatocytosis and hemochromatosis not due to transfusion, positive family history, and past history of perinatal edema were observed, and laboratory tests revealed elevated MCV, increased % residual red cells (%RRC) in the FCM-OF test, and normal or increased EMA binding.…”

“…The generated FASTQ les were imported into SureCall v3.5 (Agilent Technologies) for variant calling. Analysis following the ltering of the obtained variants was described previously 10 . The obtained variants were ltered according to the following strategy:1) variant frequencies were below 1% in 1000G_EAS and ALL (1000 Genomes), HGDV, and dbSNP; 2) synonymous variants were excluded (nonsynonymous variants, variants associated with frameshift, insertion/deletion variants, and variants in splicing donor/acceptor sites were included); 3) variants with allele frequencies less than 30% of the total read depth were excluded; and 4) the CADD_phred was higher than 20 if obtained.…”

“…We participated in clinical research on patients with hereditary red cell membrane disorders. For this purpose, we developed a target capture sequencing (TCS) system for precise and comprehensive diagnosis of suspected hereditary red cell membrane disorders in patients 10 . Here, we report the genomic variants identi ed in Japanese patients with hereditary red cell membrane disorders, especially those related to DHSt.…”