The incidence rate of Parkinson\'s disease ranks the second among degenerative diseases of the nervous system, only lower than Alzheimer\'s disease. Early-onset Parkinson\'s disease (EPOD) refers to Parkinson\'s disease with initial symptoms appearing before the age of 50. EOPD is associated with certain genetic mutations and has distinct clinical features. This study reports a case of EOPD with mutations in both the PRKN and the APOB genes. The patient presented with the initial symptom of unstable walking at the age of 28, followed by bradykinesia, limb tremors, masked face, shuffling gait, and cogwheel rigidity in both upper limbs. The blood lipid test showed total cholesterol of 6.48 mmol/L and low-density lipoprotein cholesterol of 4.13 mmol/L. Genetic testing showed a deletion in exon 5 and a point mutation [c.850G>C(p.Gly284Arg)] in exon 7 of the PRKN gene, as well as a point mutation [c.10579C>T(p.Arg3527Trp)] in exon 26 of the APOB gene. Based on these clinical manifestations and examination results, the patient was diagnosed with EOPD. The compound heterozygous mutations in the PRKN gene, as well as the combined mutations in the PRKN and APOB genes, are both reported for the first time, expanding the spectrum of genetic mutations associated with EOPD.
帕金森病的发病率位居神经系统退行性疾病的第二，仅次于阿尔茨海默病。早发型帕金森病(early-onset Parkinson’s disease，EOPD)指50岁前出现首发症状的帕金森病。EOPD与基因突变有一定的关系，并有独特的临床特征。本文报告1例PRKN基因合并APOB基因突变的EOPD，该患者于28岁时出现行走不稳的首发症状，后续出现动作迟缓、四肢震颤等症状。体格检查示：面具脸，慌张步态，双上肢肌张力齿轮样增高。总胆固醇6.48 mmol/L，低密度脂蛋白胆固醇4.13 mmol/L。PRKN基因外显子5缺失，外显子7点突变[c.850G>C(p.Gly284Arg)]；APOB基因外显子26点突变[c.10579C>T(p.Arg3527Trp)]。根据上述临床表现及检查结果，该患者被诊断为EOPD。PRKN基因的复合杂合突变及PRKN基因合并APOB基因突变均为首次报道，这丰富了EOPD的基因突变类型谱。.

The etiology of giant cell arteritis (GCA) and its predictors are incompletely understood. Previous studies have indicated reduced risk of future development of GCA in individuals with obesity and/or diabetes mellitus. There is limited information on blood lipids before the onset of GCA. The objective of the study was to investigate the relation between apolipoprotein levels and future diagnosis of GCA in a nested case-control analysis.
Individuals who developed GCA after inclusion in a population-based health survey (the Malmö Diet Cancer Study; N = 30,447) were identified by linking the health survey database to the local patient administrative register and the national patient register. A structured review of medical records was performed. Four controls for every validated case, matched for sex, year of birth, and year of screening, were selected from the database. Anthropometric measures, self-reported physical activity, based on a comprehensive, validated questionnaire, and non-fasting blood samples had been obtained at health survey screening. Concentrations of apolipoprotein A-I (ApoA-I) and apolipoprotein B (ApoB) in stored serum were measured using an immunonephelometric assay. Potential predictors of GCA were examined in conditional logistic regression models.
There were 100 cases with a confirmed clinical diagnosis of GCA (81% female; mean age at diagnosis 73.6 years). The median time from screening to diagnosis was 12 years (range 0.3-19.1). The cases had significantly higher ApoA-I at baseline screening compared to controls (mean 168.7 vs 160.9 mg/dL, odds ratio [OR] 1.57 per standard deviation (SD); 95% confidence interval [CI] 1.18-2.10) (SD 25.5 mg/dL). ApoB levels were similar between cases and controls (mean 109.3 vs 110.4 mg/dL, OR 0.99 per SD; 95% CI 0.74-1.32) (SD 27.1 mg/dL). The ApoB/ApoA1 ratio tended to be lower in cases than in controls, but the difference did not reach significance. The association between ApoA-I and GCA development remained significant in analysis adjusted for body mass index and physical activity (OR 1.48 per SD; 95% CI 1.09-1.99).
Subsequent development of GCA was associated with significantly higher levels of ApoA-I. These findings suggest that a metabolic profile associated with lower risk of cardiovascular disease may predispose to GCA.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder typically caused by low density lipoprotein receptor (LDLR) gene mutation. Herein, we reported a FH pedigree with polygenic variants: LDLR, apolipoprotein B (APOB), and epoxide hydrolase 2 (EPHX2).
METHODS: A 10-year-old boy mainly presented multiple skin xanthomas and hypercholesterolemia. His family visited our hospital and was performed with pedigree whole exome sequencing (WES) at 20 + 3 weeks gestation of the mother\'s second pregnancy.
METHODS: Based on the clinical features and genetic analysis, the pedigree was diagnosed with familial hypercholesterolemia.
METHODS: After genetic counseling, the couple opted to continue the pregnancy. Treatment advice and follow-up were offered to them.
RESULTS: A novel compound heterozygous LDLR mutation: c.1009G>T and c.68-2A>G, derived from his parents respectively was revealed through pedigree WES, meanwhile, a maternal APOB gene variant: c.1670A>G and a paternal EPHX2 gene variant: c.548 dup of the proband were found together. Furthermore, the same compound heterozygous LDLR mutation as his was confirmed in his sister without APOB and EPHX2 variants in her fetal stage.
CONCLUSIONS: WES combined with clinical features is essential for the diagnosis of FH, however, prenatal genetic testing results might bring more challenges to prenatal genetic counseling. Furthermore, it is more important to provide the guidance and early intervention for such families in the long run.

Primary hypocholesterolemia (or hypobetalipoproteinemia) is a rare disorder of lipoprotein metabolism that may be due to a polygenic predisposition or a monogenic disease. Among these, it is possible to differentiate between symptomatic and asymptomatic forms, in which, in the absence of secondary causes, the initial clinical suspicion is plasma ApoB levels below the 5th percentile of the distribution by age and sex. Here we describe the differential diagnosis of a case of asymptomatic hypocholesterolemia. We studied proband\'s clinical data, the lipid profile of the proband and her relatives and the clinical data of the family relevant to carry out the differential diagnosis. We performed a genetic study as the diagnostic test. The information obtained from the differential diagnosis suggested a heterozygous hypobetalipoproteinemia due to PCSK9 loss-of-function variants. The diagnostic test revealed, in the proband, the presence of a heterozygous PCSK9 frame-shift variant of a maternal origin. Plasma levels of LDL cholesterol and PCSK9 of the patient and her relatives were compatible with the segregation of the variant revealed. In conclusion, the diagnostic test performed confirmed the suspected diagnosis of the proband as asymptomatic familial hypobetalipoproteinemia due to a loss-of-function variant in the PCSK9 gene.

BACKGROUND In Malaysia, the prevalence of genetically confirmed heterozygous familial hypercholesterolemia (FH) was reported as 1 in 427. Despite this, FH remains largely underdiagnosed and undertreated in primary care. CASE REPORT In this case series, we report 3 FH cases detected in primary care due to mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein-B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. The mutations in case 1 (frameshift c.660del pathogenic variant in LDLR gene) and case 2 (missense c.10579C>T pathogenic variant in APOB gene) were confirmed as pathogenic, while the mutation in case 3 (missense c.277C>T mutation in PCSK9 gene) may have been benign. In case 1, the patient had the highest LDL-c level, 8.6 mmol/L, and prominent tendon xanthomas. In case 2, the patient had an LDL-c level of 5.7 mmol/L and premature corneal arcus. In case 3, the patient had an LDL-c level of 5.4 mmol/L but had neither of the classical physical findings. Genetic counseling and diagnosis were delivered by primary care physicians. These index cases were initially managed in primary care with statins and therapeutic lifestyle modifications. They were referred to the lipid specialists for up-titration of lipid lowering medications. First-degree relatives were identified and referred for cascade testing. CONCLUSIONS This case series highlights different phenotypical expressions in patients with 3 different FH genetic mutations. Primary care physicians should play a pivotal role in the detection of FH index cases, genetic testing, management, and cascade screening of family members, in partnership with lipid specialists.

暂无摘要。

Previous studies have shown both dysglycaemia and hyperuricemia are associated with an increased risk of atrial fibrillation (AF), while the relationship between serum uric acid (SUA) levels and AF in different fasting glucose patterns (FBG) is unclear. Therefore, this study aimed to determine the association between SUA and AF in different FBG patterns.
A total of 1840 patients in this case-control study were enrolled, including 920 AF patients and 920 controls. Patients were divided into three groups according to the different FBG patterns: normoglycemic, impaired fasting glucose (IFG), and diabetes mellitus (DM). Multivariate logistic regression models were performed to evaluate the relationship between SUA and AF in different FBG patterns. Pearson correlation analysis was used to explore the correlation between SUA and metabolic factors. Receiver operating characteristic (ROC) curve models indicated the diagnostic efficiency of SUA for diagnosing AF.
SUA was independently associated with AF after adjusting for all confounding factors in different FBG patterns(normoglycemic: OR=1.313, 95% CI:1.120-1.539; IFG: OR=1.386, 95% CI:1.011-1.898; DM: OR=1.505, 95% CI:1.150-1.970). Pearson\'s correlation analysis suggested that SUA in AF patients was correlated with several different metabolic factors in different FBG patterns (p<0.05). ROC curve analysis showed that SUA in the normoglycemic group combined with CHD and APOB [AUC: 0.906 (95% CI: 0.888-0.923)], in the IFG group combined with CHD and Scr [AUC: 0.863 (95% CI: 0.820-0.907)], in the DM group combined with CHD and SBP [AUC: 0.858 (95% CI: 0.818-0.898)] had the highest AUC for predicting AF.
Findings implied a significant association between SUA and AF in different FBG patterns and provide specific models combined with other factors (CHD, APOB, SCr, SBP), which might contribute to the diagnosis of AF.

Objective: To summarize the genotypes and clinical characteristics of homozygous family hypobetalipoproteinemia (Ho-FHBL) caused by apolipoprotein B (APOB) gene variations. Methods: The clinical, laboratory, genetic, and liver histology data of a boy with Ho-FHBL managed in the hepatology ward of the Children\'s Hospital of Fudan University in May 2021 were retrospectively analyzed. The literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China VIP database, China Biology Medicine disc and PubMed database (up to May 2022) with \"familial hypobetalipoproteinemia\" or \"hypobetalipoproteinemias\" or \"hypo beta lipoproteinemia\" or \"hypolipoproteinemias\" as the search terms. All relevant literatures were reviewed to summarize the clinical and genetic features of Ho-FHBL caused by APOB gene variations. Results: The male patient was admitted to the hospital due to abnormal liver function tests for 8 months at the age of 4 years and 6 months. Blood biochemistry showed transaminitis and abnormally low serum levels of lipids. Liver biopsy revealed fatty liver with inflammation and early cirrhosis (Brunt score was F3G2S4). Whole exome sequencing revealed two novel variants of APOB gene (c.3745C>T, p.Q1249 * from the father and c.4589_4592delinsAGGTAGGAGGTTTAACTCCTCCTACCT, p.T1530Kfs * 12 from the mother). He was diagnosed as Ho-FHBL caused by APOB gene compound heterozygous variations. Literature search retrieved 36 English literatures and 0 Chinese literature. A total of 55 (23 males and 32 females) Ho-FHBL cases, including this one, were caused by 54 APOB gene pathogenic variants (23 frameshift, 15 nonsense, 7 missense, 8 splice and 1 gross deletions). The age of the last follow-up was between 1 month and 75 years. Among them, 28 cases had lipid malabsorption, 19 cases had early dysplasia, 12 cases had no symptoms. Twenty-one patients had symptoms related to fat soluble vitamin deficiency, including 14 cases of acanthocytosis, 10 cases of neurological symptoms, and 6 cases of ocular lesions. Thirty-four patients had liver involvement, including 25 cases of elevated transaminase, 21 cases of fatty liver, 15 cases of hepatomegaly, 9 cases of liver fibrosis, 3 cases of liver cirrhosis, 1 case of hepatic hemangioma and 1 case of liver neoplastic nodule. Conclusions: The variants of APOB gene in Ho-FHBL are mainly frameshift and nonsense variations. Patients may have lipid malabsorption and (or) early dysplasia, or symptom-free. Liver involvement is common.
目的： 总结APOB基因变异致纯合型家族性低β脂蛋白血症（Ho-FHBL）的基因型与临床特点。 方法： 回顾性病例总结2021年5月复旦大学附属儿科医院肝病病区诊治的1例Ho-FHBL患儿的病史、体征、实验室检查、肝脏病理等临床资料及基因检测的特点，并分别以“家族性低β脂蛋白血症”“低β脂蛋白血症”“低β-脂蛋白血症”“低脂蛋白血症”“familial hypobetalipoproteinemia”“hypobetalipoproteinemias”“hypo beta lipoproteinemia”“hypolipoproteinemias”为检索词，对中国知网、万方、维普、中国生物医学文献数据库、PubMed数据库建库至2022年5月的相关文献进行检索，总结APOB基因变异致Ho-FHBL的临床及遗传学特点。 结果： 患儿，男，4岁6月龄，因“发现肝功能异常8个月”入院，血生化检测提示转氨酶升高，血脂减低。肝组织活检提示脂肪性肝炎伴早期肝硬化形成（Brunt评分F3G2S4），全外显子组测序发现APOB基因2种新变异（c.3745C>T，p.Q1249*，父亲杂合携带；c.4589_4592delinsAGGTAGGAGGTTTAACTCCTCCTACCT，p.T1530Kfs*12，母亲杂合携带），诊断为APOB基因复合杂合变异所致的Ho-FHBL。文献检索到英文文献36篇，中文文献0篇，结合本例，合计55例APOB基因变异致Ho-FHBL，其中男23例、女32例，末次随访年龄1月龄至75岁。共检测到APOB基因致病性变异54种，包括23种移码变异、15种无义变异、8种剪接位点变异、7种错义变异与1种大片段缺失。55例Ho-FHBL患者中28例表现为脂质吸收不良、19例表现为早期生长发育不良、12例无症状。21例患者出现脂溶性维生素缺乏相关表现，其中棘红细胞增多症14例、神经症状10例、眼部病变6例。34例患者肝脏受累，包括转氨酶升高25例、脂肪肝21例、肝肿大15例、肝纤维化9例、肝硬化3例、肝血管瘤和肝肿瘤性结节各1例。 结论： Ho-FHBL中APOB基因变异以移码变异与无义变异为主，患者可表现为脂质吸收不良和（或）早期生长发育不良，也可无任何症状，肝脏受累多见。.

Hereditary familial hypobetalipoproteinemia (FHBL) is a syndrome caused by variants in the APOB gene, that cause a defect in the secretion and mobilization of liver lipids to peripheral tissues, associated with the synthesis of truncated ApoB100 apolipoproteins. This condition causes significant reduction in total cholesterol (TC), low-density lipoproteins (LDL), very low-density proteins (VLDL) and serum triglyceride levels, with unchanged high-density lipoprotein (HDL) cholesterol levels. Herein we present the case of a middle-aged woman diagnosed with FHBL and hepatic steatosis, heterozygous for c.4698C>A; (p.Tyr1566Ter) variant in APOB. The variant presented herein showed high expressiveness in the two generations of individuals analyzed and has not yet being described in the medical literature. Early diagnosis and screening for associated metabolic comorbidities such as metabolic fatty liver disease and its subsequent progression to fibrosis are the two main goals in the treatment of this condition, in order to prevent medium to long term potential complications.

The relationship between apolipoprotein B (APOB) and atrial fibrillation (AF) is less well-known. We aimed to investigate the association between APOB and AF by gender. We conducted a case-control study including 1913 consecutive hospitalized patients to analyze the association between APOB and AF. 950 AF patients and 963 age-, sex-matched non-AF patients with sinus rhythm were evaluated. T-test, Mann-Whitney test, ANOVA, and Chi-square analysis were performed to analyze baseline data and intergroup comparisons. Pearson\'s correlation tests or Spearman correlation tests were performed to determine the interrelationships. Multiple regression analysis was performed to adjust for covariables. The receiver operator characteristic (ROC) curve was constructed to examine the performance of APOB. AF patients had lower APOB (P < 0.001) and an independent negative association between APOB and AF in both genders adjusting for confounding factors (OR 0.121, 95% CI 0.067-0.220, P < 0.001), regardless of statin use. APOB was positively correlated with total cholesterol (TC) (r = 0.529, p < 0.001), low-density lipoprotein cholesterol (LDL-C) (r = 0.545, p < 0.001), apolipoprotein A1 (APOA1) (r = 0.083, p < 0.001), and albumin (ALB) (r = 0.134, p < 0.001). ROC curve analysis showed that APOB level = 0.895 g/L was the most optimal cut-off value, the area under the ROC curve was 0.722. This study shows a protective association of APOB with AF in men and women. It implies APOB may be a potential biomarker for AF with a promising cut-off point of 0.895 g/L and may involve initiating and maintaining AF along with several metabolic factors.