A novel biallelic LMNB2 variant in a patient with progressive myoclonus epilepsy and ataxia: A case of laminopathy.

The report of LMNB2-related progressive myoclonus epilepsy and ataxia due to missense homozygous c.473G>T variant.

Whole-Exome Sequencing Identifies Three Candidate Homozygous Variants in a Consanguineous Iranian Family with Autism Spectrum Disorder and Skeletal Problems.

Autism spectrum disorder (ASD) is characterized by 3 core symptoms with impaired social communication, repetitive behavior, and/or restricted interests in early childhood. As a complex neurodevelopmental disorder (NDD), the phenotype and severity of autism are extremely heterogeneous. Genetic factors have a key role in the etiology of autism. In this study, we investigated an Azeri Turkish family with 2 ASD-affected individuals to identify probable ASD-causing variants. First, the affected individuals were karyotyped in order to exclude chromosomal abnormalities. Then, whole-exome sequencing was carried out in one affected sibling followed by cosegregation analysis for the candidate variants in the family. In addition, SNP genotyping was carried out in the patients to identify possible homozygosity regions. Both proband and sibling had a normal karyotype. We detected 3 possible causative variants in this family: c.5443G>A; p.Gly1815Ser, c.1027C>T; p.Arg343Trp, and c.382A>G; p.Lys128Glu, which are in the FBN1, TF, and PLOD2 genes, respectively. All of the variants cosegregated in the family, and SNP genotyping revealed that these 3 variants are located in the homozygosity regions. This family serves as an example of a multimodal polygenic risk for a complex developmental disorder. Of these 3 genes, confluence of the variants in FBN1 and PLOD2 may contribute to the autistic features of the patient in addition to skeletal problems. Our study highlights the genetic complexity and heterogeneity of NDDs such as autism. In other words, in some patients with ASD, multiple rare variants in different loci rather than a monogenic state may contribute to the development of phenotypes.

The role of inflammatory cytokines and tumor associated macrophages (TAMs) in microenvironment of pancreatic cancer.

Pancreatic cancer is considered as one of the most lethal types of cancer due to its poor prognosis and lack of effective therapeutic approaches. Although many studies have been done on pancreatic cancer, the current treatment methods did not exhibit successful results. Hence, novel strategies are needed for treatment of pancreatic cancer. The microenvironment of pancreatic cancer contains many factors such as inflammatory cytokines and tumor associated macrophages (TAMs), which influence the tumor's status. These factors can be upregulated and consequently lead to exacerbation of tumor progression. Understanding the role of pro- and anti-inflammatory cytokines and the function of TAMs in the pancreatic cancer microenvironment might lead to development and improvement of novel strategies in the diagnosis and treatment of pancreatic cancer and may result in promising treatments for this type of cancer.