Dataset Information

Analysis of a Chinese Pedigree With Familial Chylomicronemia Syndrome Reveals Two Novel LPL Mutations by Whole-Exome Sequencing.

ABSTRACT: Familial chylomicronemia syndrome (FCS) is a rare monogenic autosomal recessive disease caused by loss-of-function mutations in genes involved in chylomicron breakdown through hydrolysis of triglycerides into free fatty acids. Patients are often diagnosed in early childhood with extremely high triglyceride levels and symptoms including abdominal pain, eruptive cutaneous xanthomata, hepatosplenomegaly, and significant cognitive, psychological, and social impairment. The most serious medical condition suffered by FCS patients is recurrent acute pancreatitis. Lipoprotein lipase (LPL) gene mutation accounts for majority of the known pathogenic mutations. Early diagnosis and strict low-fat diet are critical for successful management of the triglyceride concentration to lower the risk of pancreatitis. The true prevalence of FCS in China is unknown and here we report a Chinese female preterm neonate presented with an extremely high triglyceride level of 22.11 mmol/L on day 13 after birth. Clinical and laboratory workup including whole-exome sequencing revealed two novel compound heterozygous LPL mutations (c.406G > C and c.829G > C) that are co-segregated with her non-consanguineous parents, consistent with autosomal recessive inheritance. A diagnosis of FCS based on clinical, biochemical, and genetic ground was made to guide her management.

SUBMITTER: Liu Y

PROVIDER: S-EPMC7379882 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Analysis of a Chinese Pedigree With Familial Chylomicronemia Syndrome Reveals Two Novel <i>LPL</i> Mutations by Whole-Exome Sequencing.

Liu Ying Y Lan Zhangzhang Z Zhao Fang F Zhang Shuangchuan S Zhang Wenyong W

Frontiers in genetics 20200717

Familial chylomicronemia syndrome (FCS) is a rare monogenic autosomal recessive disease caused by loss-of-function mutations in genes involved in chylomicron breakdown through hydrolysis of triglycerides into free fatty acids. Patients are often diagnosed in early childhood with extremely high triglyceride levels and symptoms including abdominal pain, eruptive cutaneous xanthomata, hepatosplenomegaly, and significant cognitive, psychological, and social impairment. The most serious medical condi ...[more]

PMID: 32765589

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Project description:IMPORTANCE:Parkinson disease (PD) is a progressive neurodegenerative disease for which susceptibility is linked to genetic and environmental risk factors. OBJECTIVE:To identify genetic variants contributing to disease risk in familial PD. DESIGN, SETTING, AND PARTICIPANTS:A 2-stage study design that included a discovery cohort of families with PD and a replication cohort of familial probands was used. In the discovery cohort, rare exonic variants that segregated in multiple affected individuals in a family and were predicted to be conserved or damaging were retained. Genes with retained variants were prioritized if expressed in the brain and located within PD-relevant pathways. Genes in which prioritized variants were observed in at least 4 families were selected as candidate genes for replication in the replication cohort. The setting was among individuals with familial PD enrolled from academic movement disorder specialty clinics across the United States. All participants had a family history of PD. MAIN OUTCOMES AND MEASURES:Identification of genes containing rare, likely deleterious, genetic variants in individuals with familial PD using a 2-stage exome sequencing study design. RESULTS:The 93 individuals from 32 families in the discovery cohort (49.5% [46 of 93] female) had a mean (SD) age at onset of 61.8 (10.0) years. The 49 individuals with familial PD in the replication cohort (32.6% [16 of 49] female) had a mean (SD) age at onset of 50.1 (15.7) years. Discovery cohort recruitment dates were 1999 to 2009, and replication cohort recruitment dates were 2003 to 2014. Data analysis dates were 2011 to 2015. Three genes containing a total of 13 rare and potentially damaging variants were prioritized in the discovery cohort. Two of these genes (TNK2 and TNR) also had rare variants that were predicted to be damaging in the replication cohort. All 9 variants identified in the 2 replicated genes in 12 families across the discovery and replication cohorts were confirmed via Sanger sequencing. CONCLUSIONS AND RELEVANCE:TNK2 and TNR harbored rare, likely deleterious, variants in individuals having familial PD, with similar findings in an independent cohort. To our knowledge, these genes have not been previously associated with PD, although they have been linked to critical neuronal functions. Further studies are required to confirm a potential role for these genes in the pathogenesis of PD.

Dataset Information

Analysis of a Chinese Pedigree With Familial Chylomicronemia Syndrome Reveals Two Novel LPL Mutations by Whole-Exome Sequencing.

Publications

Analysis of a Chinese Pedigree With Familial Chylomicronemia Syndrome Reveals Two Novel <i>LPL</i> Mutations by Whole-Exome Sequencing.

Similar Datasets

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