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

Identifying diabetes from conjunctival images using a novel hierarchical multi-task network

Diabetes can cause microvessel impairment. However, these conjunctival pathological changes are not easily recognized, limiting their potential as independent diagnostic indicators. Therefore, we designed a deep learning model to explore the relationship between conjunctival features and diabetes, and to advance automated identification of diabetes through conjunctival images. Images were collected from patients with type 2 diabetes and healthy volunteers. A hierarchical multi-tasking network model (HMT-Net) was developed using conjunctival images, and the model was systematically evaluated and compared with other algorithms. The sensitivity, specificity, and accuracy of the HMT-Net model to identify diabetes were 78.70%, 69.08%, and 75.15%, respectively. The performance of the HMT-Net model was significantly better than that of ophthalmologists. The model allowed sensitive and rapid discrimination by assessment of conjunctival images and can be potentially useful for identifying diabetes

Image1_Identification of two rare NPRL3 variants in two Chinese families with familial focal epilepsy with variable foci 3: NGS analysis with literature review.TIF

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.</p

Phylogenetic and Temporal Dynamics of Human Immunodeficiency Virus Type 1 CRF01_AE in China

<div><p>To explore the epidemic history of HIV-1 CRF01_AE in China, 408 fragments of gag gene sequences of CRF01_AE sampled in 2002–2010 were determined from different geographical regions and risk populations in China. Phylogenetic analysis indicates that the CRF01_AE sequences can be grouped into four clusters, suggesting that at least four genetically independent CRF01_AE descendants are circulating in China, of which two were closely related to the isolates from Thailand and Vietnam. Cluster 1 has the most extensive distribution in China. In North China, cluster 1 and cluster 4 were mainly transmitted through homosexuality.The real substance of the recent HIV-1 epidemic in men who have sex with men(MSM) of North China is a rapid spread of CRF01_AE, or rather two distinctive natives CRF01_AE.The time of the most recent common ancestor (tMRCA) of four CRF01_AE clusters ranged from the years 1990.9 to 2003.8 in different regions of China. This is the first phylogenetic and temporal dynamics study of HIV-1 CRF01_AE in China.</p> </div

Sampling information for the 222 HIV-1 CRF01_AE sequences obtained from the Los Alamos HIV sequence database.

<p>Sampling information for the 222 HIV-1 CRF01_AE sequences obtained from the Los Alamos HIV sequence database.</p

Demographic and clinical information for the 186 HIV-1 CRF01_AE Infectors reported by our laboratory.

<p>Demographic and clinical information for the 186 HIV-1 CRF01_AE Infectors reported by our laboratory.</p

Estimated Substitution Rates and Dates for Transmission Clusters.

*<p>Estimates of the mean evolutionary rate (μ, substitutions.site⁻¹.year⁻¹) and the median time of the most recent common ancestor (tMRCA) for the different clusters (95% high posterior density in parentheses).</p

Demographic and clinical information for patients infected with CRF01_AE virus in North China.

<p>Demographic and clinical information for patients infected with CRF01_AE virus in North China.</p

Baysian skyline plot was estimated to reconstruct the demographic history of CRF01_AE cluster 4 in Northeast China.

<p>The x axis is the time in units of years, and the y axis is equal to the effective population size. The thick solid line is the mean estimates, the 95% HPD credible region is showed by blue areas.</p