Key result
Whole-exome sequencing identifies heterozygous SPTB and LPL mutations as pathogenic in a hereditary spherocytosis family.
Why the study?
To investigate the clinical and genetic characteristics of a family affected by hereditary spherocytosis combined with familial chylomicronemia syndrome, identify the pathogenic cause, and guide management.
This case report identifies a novel SPTB mutation and an LPL mutation causing concurrent hereditary spherocytosis and familial chylomicronemia syndrome in a single family.
Alerts clinicians to screen for coexisting lipid disorders in hereditary spherocytosis; extends SPTB spectrum but remains hypothesis-generating.
ObjectiveThis study was conducted to investigate the clinical and genetic characteristics of a family affected by hereditary spherocytosis (HS) combined with familial chylomicronemia syndrome (FCS), identify the pathogenic cause, and provide a basis for the clinical diagnosis, treatment, and genetic counseling of affected children.MethodsClinical data were collected from family members. High-throughput sequencing was performed to identify pathogenic variants in genes associated with HS and FCS in the proband. Suspected pathogenic mutations were confirmed in family members via PCR-Sanger sequencing. Bioinformatics analysis and three-dimensional protein structure prediction were also conducted.ResultsThe proband presented with severe anemia, splenomegaly, and jaundice. Genetic testing revealed a heterozygous mutation, c.6005G>A (p.Trp2002*), in the spectrin beta chain (SPTB)gene (NM_001355436.2) and a missense mutation, c.292G>A (p.Ala98Thr), in the lipoprotein lipase (LPL) gene (NM_000237.3). The SPTB c.6005G>A (p.Trp2002*) mutation was inherited from the mother, who exhibited mild anemia, jaundice, and splenomegaly. The LPL c.292G>A (p.Ala98Thr) mutation was inherited from the father, who had hypertriglyceridemia. The SPTB c.6005G>A (p.Trp2002*) mutation is extremely rare in the general population.ConclusionThe heterozygous mutations SPTB c.6005G>A (p.Trp2002*) and LPL c.292G>A (p.Ala98Thr) are the pathogenic causes in this family and provide a basis for clinical management and genetic counseling. Based on the HGMD, 1000G, and ExAC databases, the SPTB c.6005G>A (p.Trp2002*) mutation is reported here for the first time, enriching the mutation spectrum of the SPTB gene.
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Qin et al. (2026) studied this question. The family with hereditary spherocytosis exhibited heterozygous mutations SPTB c.6005G>A (p.Trp2002*) and LPL c.292G>A (p.Ala98Thr) as pathogenic causes.
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