A nonsense germline mutation in the LPL gene in a 1-month-old infant: case report with review of literature

Abstract

Abstract Background Primary hypertriglyceridemia (HTG) is a very rare autosomal recessive disorder caused by the mutations of the genes related with triglyceride metabolism, including apolipoproteins and lipoprotein lipase (LPL) among others. Germline mutations in the LPL gene cause familial LPL deficiency with an incidence of about 1:1,000,000. It is often diagnosed in childhood and consanguinity is common. Case presentation We present here a LPL nonsense variant in an infant with heterozygous carriers (parents) of one of each variation detected in the infant. The infant presented with recurrent vomiting, diarrhoea, and haematochezia at 1 month of age. A diagnosis of familial HTG in the infant was made from the clinical manifestations and observation of a lipemic blood sample. Next-generation sequencing identified two pairs of variants in the LPL gene in the patient: chr8:g.19961024G>A; c.1263G>A; p.Trp421Ter and chr8:g.19962221T>G; c.1427+2T>G which were confirmed and validated by Sanger sequencing. The nonsense variant in exon 8 (chr8:g.19961024G>A (HET); c.1263G>AC; p.Trp421Ter) of the LPL gene was detected only in the father, while the 5ʹ splice site variant in intron 9 (chr8:g.19962221T>G (HET); c.1427+2T>G) was detected only in the mother. Thus, the infant manifesting HTG inherited one recessive gene from each of the carrier parents. There were no de novo mutations in the index patient. Based on the clinical findings and genetic test results, it was concluded that the infant suffers from compound heterozygous familial HTG. Conclusions The current case of the infant with germline mutations in the LPL gene resulting in very severe HTG highlights the importance of genetic counseling. Genetic identification of the pathogenic variants is essential to strategize genetic therapy whenever feasible. The consanguineous nature of the parents is the most probable identified risk factor for the germline mutation in the LPL gene.