Background: Olfaction in animals is important for host localization, mating and reproduction in heterogeneous chemical environments. Studying the molecular basis of olfactory receptor neurons (ORNs) systems can elucidate the evolution of olfaction and associated behaviours. Odorant receptors (ORs) in insects have been identified, particularly in the holometabolous model Drosophila, and some of them have been functionally studied. However, ORs in the locust—a hemimetabolous model insect and the most important insect crop pest—have not yet been identified, hindering our understanding of locust olfaction. Here, we report for the first time four putative ORs in Locusta migratoria: LmigOR1, LmigOR2, LmigOR3 and LmigOR4. Results: These four putative OR genes encoded proteins with amino acids of 478, 436, 413 and 403 respectively. Sequence identity among them ranged from 19.7% to 35.4%. All ORs were tissue-specifically expressed in olfactory organs, without sex-biased characteristics. However, LmigOR1, LmigOR3 and LmigOR4 were only expressed in the antenna, while LmigOR2 could also be detected in mouthparts. In situ hybridization demonstrated that the LmigOR1antisense probe labelled olfactory receptor neurons (ORNs) in almost all segments of the antenna, but only a few segments housed ORNs expressing LmigOR2. The number of neurons labelled by LmigOR1 antisense probes in each antennal segment was much greater (>10 neurons/segment) than that labelled by LmigOR2 probes (generally 1–3 neurons/segment). Furthermore, some of the labelled neurons could be attributed to the basiconic sensilla, but LmigOR1 and LmigOR2 were expressed in different subtypes. Conclusions: Our results strongly suggested that these newly discovered genes encode locust ORs and the differential expression patterns of LmigOR1 and LmigOR2 implied distinct functions. These results may offer insights into locust olfaction and contribute to the understanding of the evolution of insect chemoreception.

Objective: According to a recent report, the mutation of transcription factor gene BCL11B is associated with the development of neurodevelopmental disorders and immune deficiency. By analyzing both clinical features and genetic variations, this study aims to reveal the genetic etiology of four patients with neurodevelopmental disorders from two unrelated Chinese pedigrees.Methods: From the 4 cases, the clinical data were collected. The potential pathogenic gene variations were analyzed by means of based-trio whole exome sequencing (Trio-WES) and then validated through Sanger sequencing in their respective pedigrees. Furthermore, both the in vitro minigene assay and the NMD assay were performed to evaluate the impact of splicing and frameshift variants.Results: The 4 patients displayed mild-to-severe intellectual developmental disorder, which was accompanied by speech delay, dysmorphic facies, and serious caries. In addition, the extended phenotype of developmental regression was observed in the proband from Family 1, which has been unreported previously. Molecular analysis was conducted to identify two novel heterozygous variants in the BCL11B gene: a maternal splicing variant c.427 + 1G > A in Family 1 and a de novo frameshift variant c.2461_2462insGAGCCACACCGGCG (p.Glu821Glyfs*28) in Family 2. As revealed by the in vitro minigene assay, the c.427 + 1G > A variant activated a new cryptic splice site. As confirmed by an overexpression assay, there was no significant difference in the level of mRNA and protein expression between the mutate-BCL11B (p.Glu821Glyfs*28) and the wild type. It confirms that p.Glu821Glyfs*28 variant could be an NMD escaping variant.Conclusion: The extended phenotype of BCL11B-related disorders is reported in this study to reveal the clinical and genetic heterogeneity of the disease. The study starts by identifying a splicing variant and a novel frameshift variant of the BCL11B gene, thus confirming its aberrant translation. The findings of this study expand the mutation spectrum of the genetic BCL11B gene, which not only improves the understanding of the associated neurodevelopmental disorders from a clinical perspective but also provides guidance on diagnosis and genetic counseling for patients.

Aim: To determine the etiology of a Chinese family with thrombocytopenia by analyzing the clinical features and genetic variation.Methods: Clinical profiles and genomic DNA extracts of the family members were collected for the study. Whole exome sequencing and Sanger sequencing was used to detect the associated genetic variation and verify the family co-segregation respectively. Bioinformatics analysis assessed the pathogenicity of missense mutations.Results: The study reported a 3-generation pedigree including eight family members with thrombocytopenia. The platelet counts of the patients were varied, ranging from 38 to 110 × 10⁹/L (reference range: 150–450 x 10⁹/L). The mean volumes and morphology of the sampled platelet were both normal. The bleeding abnormality and mitochondriopathy were not observed in all the patients. Clinical signs of thrombocytopenia were mild. A novel heterozygous missense variant c.79C > T (p.His27Tyr) was identified in CYCS gene associated with autosomal dominant thrombocytopenia.Conclusion: We report the first large family with autosomal dominant non-syndromic thrombocytopenia 4 in a Chinese family, a novel heterozygous missense variant c.79C > T (p.His27Tyr) was identified. The whole exome sequencing is an efficient tool for screening the variants specifically associated with the disease. The finding enriches the mutation spectrum of CYCS gene and laid a foundation for future studies on the correlation between genotype and phenotype.

Purpose: This study reports the clinical and genetic features of Brown-Vialetto-Van Laere syndrome (BVVL) type 2 in a case of uniparental disomy of chromosome 8 in mainland China and analyzes the genotype-phenotype correlation through a review of the literature of BVVL type 2 cases.Methods: The clinical characteristics, treatment, and follow-up data of the patient were summarized, and the etiology was identified by whole-exome sequencing and gene chip analysis. Correlations between the genotype and phenotype were analyzed by collecting clinical and genetic data of published cases and our patient.Results: We identified a homozygous mutation in SLC52A2 (NM_001253815.2 c.1255G>A) by trio-WES. Sanger sequencing confirmed that his father was heterozygous and his mother was wild type. Subsequently, paternal uniparental disomy of chromosome 8 [UPD (8)pat] was confirmed by chromosomal microarray analysis.The patient received long-term oral riboflavin treatment (7 mg/kg.d) and was followed up for 40 months by which time the child’s bulbar palsy, ataxia, and motor function had improved. A review of the literature and statistical analysis found that the symptoms of BVVL type 2 appear at the earliest shortly after birth and at the latest at 10 years of age. The median age of onset was 2.5 years, but the overall delay in diagnosis was a median of 5.6 years. The most common symptoms were hearing loss (83.9%), followed by muscle weakness (80.6%), visual impairment (64.5%), and ataxia (61.3%). To date, a total of 32 mutations in the SLC52A2 gene have been reported, with the most common being a missense mutation. Mutations occur throughout the length of the gene apart from at the N-terminus. In patients with missense mutations, homozygous pattern was more likely to present with ataxia as the first symptom (p < 0.05), while compound heterozygous pattern was more likely to develop respiratory insufficiency during the course of disease (p < 0.001). Moreover, patients with one missense mutation located in inside the transmembrane domain were more likely to have respiratory insufficiency than those with mutations both inside and outside the domain (p < 0.05). Riboflavin supplementation was an important factor in determining prognosis (p < 0.001).Conclusion: We report the first UPD(8)pat with SLC52A2 homozygous pathogenic mutation case in BVVL type 2, which expand the mutation spectrum of gene.

Aim: To explore the clinical imaging, laboratory and genetic characteristics of a newborn boy with isolated sulfite oxidase deficiency (ISOD) in a Chinese mainland cohort.Methods: Homocysteine and uric acid in plasma and cysteine and total homocysteine in the blood spot were assessed in a Chinese newborn patient with progressive encephalopathy, tonic seizures, abnormal muscle tone, and feeding difficulties. Whole exome sequencing and Sanger sequencing facilitated an accurate diagnosis. The pathogenicity predictions and conservation analysis of the identified mutations were conducted by bioinformatics tools.Results: Low total homocysteine was detected in the blood spot, while homocysteine and uric acid levels were normal in the plasma. S-sulfocysteine was abnormally elevated in urine. A follow-up examination revealed several progressive neuropathological findings. Also, intermittent convulsions and axial dystonia were observed. However, the coordination of sucking and swallowing was slightly improved. A novel paternal nonsense variant c.475G > T (p.Glu159^∗) and a novel maternal missense variant c.1201A > G (p.Lys401Glu) in SUOX were identified in this case by co-segregation verification.Conclusion: This is the second report of early-onset ISOD case in a non-consanguineous Chinese mainland family. Combined with the clinical characteristics and biochemical indexes, we speculated that these two novel pathogenic variants of the SUOX gene underlie the cause of the disease in this patient. Next-generation sequencing (NGS) and Sanger sequencing provided reliable basis for clinical and prenatal diagnoses of this family, it also enriched the mutation spectrum of the SUOX gene.

The COVID-19 pandemic and subsequent changes in public health policies have profoundly altered respiratory pathogen circulation patterns. This study aimed