# Case Report: Clinical and genetic analysis of a family with hereditary spherocytosis combined with familial chylomicronemia syndrome

## TL;DR

This case report describes a family with two rare genetic disorders, hereditary spherocytosis and familial chylomicronemia syndrome, and identifies the specific mutations responsible.

## Contribution

The study reports a novel mutation in the SPTB gene and confirms a rare co-occurrence of two genetic disorders in a single family.

## Key findings

- The proband has a novel SPTB mutation (c.6005G>A) and an LPL mutation (c.292G>A) causing hereditary spherocytosis and chylomicronemia.
- The SPTB mutation (c.6005G>A) is inherited from the mother and is extremely rare in the general population.
- The LPL mutation (c.292G>A) is inherited from the father and is linked to hypertriglyceridemia.

## Abstract

This 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.

Clinical 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.

The 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.

The 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.