Department of Gastroenterology, Kunming Children's Hospital, Kunming 650228, Yunnan, China.
Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children's Major Disease Research, Yunnan Medical Center for Pediatric Diseases, Yunnan Institute of Pediatrics, Kunming Children's Hospital, Kunming 650228, Yunnan, China.
Clin Chim Acta. 2021 Oct;521:264-271. doi: 10.1016/j.cca.2021.07.022. Epub 2021 Jul 27.
The aim of this study was to investigate the clinical features and genetic causes of two family cases with familial chylomicronemia syndrome (FCS). Clinical manifestations of proband 1 and her families, and also proband 2 showed severe hypertriglyceridemia, especially the triglycerides levels of two probands were extremely high. Gene sequencing results showed that the LPL genes in each of the two probands had a new mutation site. For the proband 1, a compound heterozygous mutation at c.429 (c.429 + 1G > T) was detected in the LPL gene, which was splicing mutation and inherited from her mother. Homozygous mutation was detected in the LPL gene of proband 2, the nucleotide mutation at c.802 (c.802C > T) exhibited missense mutation, his parents and brother had a heterozygous mutation at the same site. It was confirmed that the conservative lipoprotein lipase superfamily domain changed an amino acid from histidine to tyrosine at p. 268 (p. His268Tyr). Flow cytometry confirmed the deficient expression of LPL protein in two families. These results indicated that the mutation in LPL gene might be the cause of familial chylomicronemia syndrome.
本研究旨在探讨两例家族性乳糜微粒血症综合征（FCS）家系的临床特征和遗传病因。先证者 1 及其家系和先证者 2 的临床表现均为严重高甘油三酯血症，尤其两先证者的甘油三酯水平极高。基因测序结果显示，两位先证者的 LPL 基因均存在新的突变位点。先证者 1 的 LPL 基因中检测到 c.429（c.429+1G>T）复合杂合突变，为剪接突变，遗传自其母亲。先证者 2 的 LPL 基因中检测到纯合突变，c.802（c.802C>T）核苷酸突变表现为错义突变，其父母和兄弟在同一位置存在杂合突变。证实保守的脂蛋白脂肪酶超家族结构域第 268 位的氨基酸由组氨酸变为酪氨酸（p.His268Tyr）。流式细胞术证实了两个家系中 LPL 蛋白的表达缺陷。这些结果表明，LPL 基因突变可能是家族性乳糜微粒血症综合征的病因。
