BACKGROUND: Clinical observational study demonstrated that hypertension is an independent risk factor for stroke. Furthermore, both hypertension and stroke exhibit genetic predispositions. However, the genetic relationship between hypertension and stroke in first-degree relatives remains unclear.
METHODS: The Genetic effects were validated using an across-Mendelian randomization (MR) approach. The Genome-Wide Association Study summary data used in this study were obtained from a publicly available platform. The primary MR effect employed was inverse-variance weighted (IVW), and the other analysis methods included MR-Egger, weighted median, simple mode, and weighted mode. Prior to MR analysis, tests for MR_PRESSO, pleiotropy, and heterogeneity were conducted.
RESULTS: The presence of family history of hypertension significantly contributed to the genetic predisposition to various types of stroke, including ischemic stroke, subarachnoid hemorrhage, lacunar stroke, cardioembolic ischemic stroke, small vessel ischemic stroke, and large artery atherosclerosis-related ischemic stroke.
CONCLUSIONS: Briefly, hypertension in first-degree relatives has a genetic impact on the risk of stroke development. Shared genetic factors may exist between hypertension and stroke.

Sheep are important herbivorous domestic animal globally, and the Chinese indigenous sheep breed has a multitude of economically significant variations due to the diverse geographical and ecological conditions. In particular, certain native breeds exhibit a visible high litter size phenotype due to the selection pressure of natural and artificial for thousands of years, offering an ideal animal model for investigating sheep\'s fecundity. In this study, selective signal analysis was performed on public whole-genome sequencing data from 60 sheep across eight breeds to identify candidate genes related to litter size. Results revealed that a total of 34,065,017 single-nucleotide polymorphisms (SNPs) were identified from all sheep, and 65 candidate genes (CDGs) were pinpointed from the top 1% of interacted windows and SNPs between the pairwise fixation index (FST, >0.149543) and cross-population extended haplotype homozygosity (XP-EHH, >0.701551). A total of 41 CDGs (e.g. VRTN, EYA2 and MCPH1) were annotated to 576 GO terms, of which seven terms were directly linked to follicular and embryonic development (e.g. TBXT, BMPR1B, and BMP2). In addition, 73 KEGG pathways were enriched by 21 CDGs (e.g. ENTPD5, ABCD4 and RXFP2), mainly related to Hippo (TCF4, BMPR1B and BMP2), TGF-β (BMPR1B and BMP2), PI3K-Akt (ITGB4, IL4R and PPP2R5A) and Jak-STAT signalling pathways (IL20RA and IL4R). Notably, a series of CDGs was under strong selection in sheep with high litter size traits. These findings result could improve the comprehension of the genetic underpinnings of sheep litter size. Furthermore, it provides valuable CDGS for future molecular breeding.

Objective: To analyze the distribution characteristics of UGT1A1 mutant genes (including enhancers, promoters, and exons 1-5) and further explore the correlation between UGT1A1 genotype and clinical phenotypes in patients with inherited hyperunconjugated bilirubinemia. Methods: Patients diagnosed with hereditary hyperunconjugated bilirubinemia at Nanjing Second Hospital from June 2015 to December 2022 were retrospectively analyzed. The UGT1A1 gene was examined using Sanger sequencing in all patients. Complete blood count, liver function, and abdominal imaging examinations were performed. Comparison of categorical variable data using χ(2) testor Fisher percision tests. Comparison of continaous veriable data with normal distribution using t-test. Results: 112 cases (male:female ratio 81:31, aged 9-70 years) had inherited hyperunconjugated bilirubinemia, with a total of 14 mutation sites identified, of which seven were confirmed mutations, and the frequency ranged from high to low: (TA)n accounted for 50%, c.211G>A (p.G71R) accounted for 49.10%, 1456T>G (p.Y486D) accounted for 16.96%, c.686C>A (p.R229W) accounted for 12.5%, 1091C>T (p.P364L) accounted for 8.04%, and c- 3279T>G accounted for 0.982%. Simultaneously, all patients had one to four mutations, of which only one mutation was the most common (55.36%), followed by two mutations (37.5%), and rare three and four mutations (5.36% and 1.78%). There was no statistical significance in total bilirubin (TBil) levels among the four groups (F=0.652, P=0.583). One mutation was most common in (TA)n and c.211G>A (p.G71R), among which TA6/TA7 (n=10) and TA7/TA7 (n=14) mutations were statistically significant in TBil (t=2.143, P=0.043). The c.211G>A (p.G71R) heterozygous (n=9) and isolated (n=15) mutation had no statistical significance in TBil (t=0.382, P=0.706). The GS group accounted for 75%, the intermediate group accounted for 16.9%, and the CNS-Ⅱ group accounted for 8%. TBil was statistically significant among the three groups (F=270.992, P<0.001). There was no statistically significant difference (χ(2)=3.317, P=0.19) between mutation 1 (44 cases, 14 cases, and 4 cases, respectively) and mutations ≥ 2 (40 cases, 5 cases, and 5 cases, respectively) in the GS group, intermediate group, and CNS-II group. Conclusion: The number of UGT1A1 gene mutation sites may have no synergistic effect on TBil levels in patients with inherited hyperunconjugated bilirubinemia. TA7/TA7 mutations are not uncommon, and TBil levels are relatively high.
目的： 分析遗传性高非结合性胆红素血症患者尿苷二磷酸葡萄糖醛酸转移酶（UGT1A1）突变基因（包括增强子、启动子、外显子1～5）分布特征，探讨UGT1A1基因型与临床表型的关系。 方法： 回顾性分析2015年6月至2022年12月在南京市第二医院诊断为遗传性高非结合性胆红素血症的患者资料。患者均采用Sanger测序对UGT1A1基因进行检测，完成血常规、肝生物化学、腹部影像学检查。分类变量资料比较采用χ (2)检验或fisher精准检验；正态分布连续变量资料比较用t检验。 结果： 112例（男∶女为81∶31，年龄9～70岁）遗传性高非结合性胆红素血症患者，共查出14个突变位点，7个为已证实的突变，频率由高到低；(TA)n占50%、c.211G > A(p.G71R）占49.10%、1456T > G(p.Y486D）占16.96%、c.686C > A(p.R229W）占12.5%、1091C > T(p.P364L）占8.04%、c.-3279T > G占0.982%。所有患者同时存在1～4个突变，其中只有1个突变病例最多见（55.36%），其次为2个突变（37.5%），3和4个突变较为少见（分别为5.36%，1.78%）；4组间总胆红素（TBil）水平差异无统计学意义(F = 0.652，P = 0.583）。一个突变以(TA)n和c.211G > A(p.G71R）最多见，其中TA6/TA7 (n = 10）与TA7/TA7 (n = 14）突变患者TBil差异有统计学意义(t = 2.143，P = 0.043）。c.211G > A(p.G71R）杂合（n = 9）与纯合（n = 15）突变的TBil差异无统计学意义（t  = 0.382，P = 0.706）。GS组占75%，中间组占16.9%，CNS-Ⅱ组占8%，3组TBil差异有统计学意义（F = 270.992，P < 0.001）；GS组、中间组、CNS-Ⅱ组中1个突变（分别为44、14、4例）与≥2个突变（分别为40、5、5例）差异无统计学意义（χ (2) = 3.317，P = 0.19）。 结论： 遗传性高非结合性胆红素血症患者UGT1A1基因变异位点数量对TBil水平可能无叠加作用。TA7/TA7突变并不少见，TBil水平较高。.

In recent years, the prevalence of myopia has gradually increased, and it has become a significant global public health problem in the 21st century, posing a serious challenge to human eye health. Currently, it is confirmed that the development of myopia is attributed to the combined action of genes and environmental factors. Thus, elucidating the risk factors and pathogenesis of myopia is of great significance for the prevention and control of myopia. To elucidate the impact of gene-environment interaction on myopia, we used the Pubmed database to search for literature related to myopia. Search terms are as follows: myopia, genes, environmental factors, gene-environment interaction, and treatment. This paper reviews the effects of gene and environmental interaction on myopia.

Townes-Brocks syndrome (TBS) is an autosomal dominant disorder characterised by the triad of anorectal, thumb, and ear malformations. It may also be accompanied by defects in kidney, heart, eyes, hearing, and feet. TBS has been demonstrated to result from heterozygous variants in the SALL1 gene, which encodes zinc finger protein believed to function as a transcriptional repressor. The clinical characteristics of an atypical TBS phenotype patient from a Chinese family are described, with predominant manifestations including external ear dysplasia, unilateral renal hypoplasia with mild renal dysfunction, and hearing impairment. A novel heterozygous variant c.3060T>A (p.Tyr1020*) in exon 2 of the SALL1 gene was identified in this proband. Pyrosequencing of the complementary DNA of the proband revealed that the variant transcript accounted for 48% of the total transcripts in peripheral leukocytes, indicating that this variant transcript has not undergone nonsense-mediated mRNA decay. This variant c.3060T > A is located at the terminal end of exon 2, proximal to the 3\' end of the SALL1 gene, and exerts a relatively minor impact on protein function. We suggest that the atypical TBS phenotype observed in the proband may be attributed to the truncated protein retaining partial SALL1 function.

Recurring episodes of fever characterize tumor necrosis factor receptor-associated periodic syndrome (TRAPS) which is autosomal dominant. The primary symptoms of patients with TRAPS include prolonged fever, abdominal pain, muscle pain, and skin rashes. The prevalence of TRAPS appeared higher in Western countries than in Asian countries. Herein, we present the case of a 13-year-old girl who experienced intermittent fever for 8 years, with episodes that occur every 2 years. The patient demonstrated periodic fever, headache, vomiting, rash, and elevated inflammatory marker levels during the disease course. A heterozygous C55Y mutation was identified via a direct DNA sequencing of her genomic DNA. This mutation is located in exon 4 of TNFRSF1A. Genetic studies of her sister and mother revealed that they possessed the C55Y heterozygous mutation without demonstrating any clinical signs, while the father did not. Further, we conducted a thorough assessment of the literature and compiled the information from the eight TRAPS case series.

Neurologists have a difficult time identifying sporadic cerebellar ataxia. Multiple system atrophy of the cerebellar type (MSA-C), spontaneous late cortical cerebellar atrophy, and prolonged alcohol use are a few possible causes. In a group of people with sporadic cerebellar ataxia that was not MSA-C, an autosomal-dominant spinocerebellar ataxia (SCA) mutation was recently discovered. Chinese single-hospital cohort will be used in this study to genetic screen for SCA-related genes. One hundred forty individuals with CA were monitored over 8 years. Thirty-one individuals had familial CA, 109 patients had sporadic CA, 73 had MSA-C, and 36 had non-MSA-C sporadic CA. In 28 of the 31 non-MSA-C sporadic patients who requested the test, we carried out gene analysis, including SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, SCA17, SCA31, and dentatorubro-pallidoluysian atrophy (DRPLA). The control group consisted of family members of the patients. In 57% of the instances with spontaneous CA that were not MSA-C, gene abnormalities were discovered. The most frequent exception among individuals with sporadic CA was SCA6 (36%), followed by monsters in SCA1, 2, 3, 8, and DRPLA. In contrast, 75% of the patients with familial CA had gene abnormalities, the most frequent of which was SCA6 abnormality. The age of 69 vs 59 was higher, and the CAG repeat length was a minor age of 23 vs 25 in the former instances compared to the last one among individuals with SCA6 anomalies that were sporadic as opposed to familial cases. In sporadic CA, autosomal-dominant mutations in SCA genes, notably in SCA6, are common. Although the cause of the increased incidence of SCA6 mutations is unknown, it may be related to a greater age of onset and varied penetrance of SCA6 mutations.

暂无摘要。

OBJECTIVE: The aim of this study was to assess the correlation of spouse selection with short tandem repeats (STRs) in DNA and with the number of fingertip lunulae to investigate the role of heredity in spouse selection.
METHODS: We randomly selected a total of 286 couples (husband and wife) as a couple group while 200 paired subjects (a man randomly matched with a woman as a pair of subjects) were selected as a non-spouse group for DNA typing, and to investigate lunulae in spouse selection, a total of 554 couples were selected as a couple group and 500 pairs of subjects were selected as a control group.
RESULTS: A significant difference of STR matching number (a large value implies a higher genetic similarity) between spouse group and non-spouse group were observed (12.3 ± 2.7 vs. 11.8 ± 2.6; p < 0.05). A significant difference of the lunula matching number (difference of lunula counts between a paired subjects, a lower value implies a higher genetic similarity) between two groups were also observed for the lunula counts (1.55 ± 1.88 vs. 3.53 ± 2.40; p < 0.01).
CONCLUSIONS: Significant and unprecedented relationships were found between the couples and polymorphic STRs, and between spouse selection and lunula counts. Polymorphic STRs and fingertip lunulae counts provide an initial insight into the potentially important contributions that genetic characteristics may play a key role in spouse selection.

OBJECTIVE: We primarily aimed to investigate the attention network function among parents of children with autism spectrum disorder (ASD) using the Attention Network Test (ANT). The secondary objective was to observe whether the three attention networks of all participants were related to each other.
METHODS: We included 28 parents of children with ASD and 28 well-matched parents of typically developing children. All participants underwent the neuropsychological assessment and ANT test. The three distinct attention networks, including alerting, orienting, and executive control, were also measured.
RESULTS: Compared with controls, parents of children with ASD showed less-efficient alerting and executive control network (all p<0.05), but not orienting network (p=0.74). No significant correlation was found between the alerting, orienting, and executive control network for either group.
CONCLUSIONS: Our findings showed that parents of children with ASD had deficits in alerting and executive control attention functions. The deficits are indications of a broad autism phenotype.