Novel compound heterozygous mutations in OCA2 gene were identified in a Chinese family with oculocutaneous albinism.

BACKGROUND: Oculocutaneous albinism (OCA) is a group of rare autosomal recessive disorders characterized by clinical genetic heterogeneity. OCA type II (OMIM: 203200) is the most common subtype among African and African Americans, primarily caused by pathogenic variants in the OCA2 (HGNC ID: 8101) gene. In this study, we presented a Chinese family with OCA and reported two novel variants in the OCA2 gene. METHODS: Whole-exome sequencing (WES) was performed to identify pathogenic variants in the proband. The candidate variants were subsequently validated using Sanger sequencing and QPCR assay. Additionally, bioinformatics analyses were employed to predict the deleteriousness and conservation of the identified mutations. RESULTS: In the 16-year-old male proband, two novel compound heterozygous OCA2 variants, NM_000275.3: c.1640T>G (NP_000266.2: p.L547R) and an exons 10-19 deletion variant, were identified. Meanwhile, a reported heterozygous variant c.1441G>A/p.A481T (NM_000275.3, NP_000266.2) in the OCA2 gene was also found in the proband. Sanger sequencing confirmed that the two variants c.1441G>A/p.A481T and c.1640T>G/p.L547R were inherited from his father. Moreover, qPCR assay revealed that the exons 10-19 deletion was inherited from the mother, his sister also carried this variant. Fortunately, the variant was not detected in the amniotic fluid of the proband's sister. Multiple online bioinformatics tools predicted the variant c.1640T>G to be damaging, leading to the replacement of a highly conserved leucine with an arginine. The gross exon 10-19 deletion in the OCA2 gene resulted in a truncated, non-functional protein losing the 3-9 transmembrane α-helices domains. According to the American College of Medical Genetics and Genomics classification, these three variants in the OCA2 gene were evaluated as likely pathogenic. CONCLUSION: This study has identified two novel compound variants in the OCA2 gene and a previously reported variant in a Chinese family with OCA. By expanding the mutation spectrum of the OCA2 gene, our findings contribute to a better understanding of the genetic basis of OCA.

Stenting with high-intensity focused ultrasound ablation for distal biliary obstruction caused by pancreatic carcinoma: a meta-analysis.

Introduction: Between 42% and 77% of patients with distal malignant biliary obstruction (MBO) suffer from pancreatic carcinoma (PC). Aim: To analyse the clinical efficacy of stenting accompanied by high-intensity focused ultrasound (HIFU) ablation in patients with distal MBO from PC. Material and methods: Relevant articles published through March 2021 were identified in the Pubmed, Cochrane Library, Embase, Wanfang, VIP, and CNKI databases. RevMan v5.3 and Stata v12.0 were used for the meta-analysis. Results: Twenty-nine articles were initially identified, and 5 of these were eventually included. These articles described 142 patients who underwent biliary stenting alone and 132 patients who underwent biliary stenting with HIFU ablation. The pooled Δ total bilirubin (TBIL) values were comparable between the 2 treatment groups (p = 0.10). The pooled stent dysfunction rate was significantly greater in the group with stenting alone (p = 0.03), and the pooled HR for the stent patency duration indicated that the duration of stent patency was increased in the stenting with HIFU ablation group (p < 0.0001). Overall survival rates were significantly longer in the stenting with HIFU ablation group (p < 0.0001). HIFU ablation was associated with an 80% pooled clinical response rate. The pooled cholangitis (p = 0.47) and pancreatitis (p = 0.56) rates were comparable between the 2 groups. Funnel plots did not reveal any significant evidence of endpoint-associated publication bias. Conclusions: Stenting with HIFU ablation increased both stent patency and overall survival in patients with distal MBO caused by PC compared to stenting alone.

Identification of two rare NPRL3 variants in two Chinese families with familial focal epilepsy with variable foci 3: NGS analysis with literature review.

Background: The GAP Activity Towards Rags 1 (GATOR1) complex, which includes DEPDC5, NPRL2, and NPRL3, plays a key role in epilepsy. It has been reported that focal epilepsy is associated with mutations in the NPRL3 gene in some cases. We report two rare mutations in the NPRL3 gene in two unrelated Chinese families with focal epilepsy in this study. Methods: The proband and her brother in family E1 first experienced seizures at 1.5 and 6 years of age, respectively. Despite resection of epileptogenic foci, she still suffered recurrent seizures. The first seizure of a 20-year-old male proband in family E2 occurred when he was 2 years old. To identify pathogenic variants in these families, whole-exome sequencing (WES) was performed on genomic DNA from peripheral blood. Results: In family E1, the trio-WES analysis of the proband and her brother without apparent structural brain abnormalities identified a heterozygous variant in the NPRL3 gene (c.954C>A, p.Y318*, NM_001077350.3). In family E2, the proband carried a heterozygous NPRL3 mutation (c.1545-1G>C, NM_001077350.3). Surprisingly, the mothers of the two probands each carried the variants, but neither had an attack. Bioinformatics analysis predicted that the mutation (c.954C>A) was in the highly conserved amino acid residues of NPRL3, which affected the α-helix of NPRL3 protein, leading to a truncated protein. The splice variant (c.1545-1G>C) resulted in the loss of the last exon of the NPRL3 gene. Conclusion: The results of this study provide a foundation for diagnosing NPRL3-related epilepsy by enriching their genotypes and phenotypes and help us identify the genetic etiologies of epilepsy in these two families.

[Expression and Clinical Significance of Focal Adhesion Kinase in Patients with Acute Leukemia].

OBJECTIVE: To explore the expression of focal adhesion kinase (FAK) in patients with acute leukemia (AL) and its clinical significance. METHODS: The FAK mRNA levels in leukemic cells of 50 patients with AL and bone marrow mononuclear cells(BMMNC) of 10 healthy controls were measured by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The bone marrow cell chromosomes were prepared using direct and short term culture, and karyotyping was performed by R-banding technique. RESULTS: The expression positive rate of FAK mRNA in leukemic cells of 50 patients with AL was 66.0%, which was significantly higher than that in normal controls (20.0%) (P<0.05). The expression positive rates and levels of FAK mRNA in both ALL and ANLL cells were statistically significantly higher than those in normal controls (P<0.05), but the difference between ALL and ANLL cells was not significant (P>0.05). All the expression- positive rates and levels of FAK mRNA in newly diagnosed AL patients and the relapsed AL patients were significantly higher than those in normal controls (P<0.05), but the difference between the newly diagnosed AL patients and the relapsed AL patients was not significant (P>0.05). Morecover, the expression plsitive rate and levels of FAK mRNA in the remitted patients were lower than those in newly diagnosed and relapsed patients (P<0.05), but were no statistically significantly different from normal controls (P>0.05). The expression- positive rate and level of FAK mRNA in the AL patients with abnormal karyotype were significantly higher than those in the AL patients without abnormal karyotype (P<0.05). CONCLUSION: FAK mRNA over-express in the leukemia patients, which may be related with the outome of disease, possibly providing novel targeting sites for the treatment of leukemia.