A Case of Geroderma Osteodysplasticum Syndrome: Unique Clinical Findings

Geroderma osteodysplasticum (GO; MIM 231070) is characterized by a typical progeroid facial appearance, wrinkled, lax skin, joint laxity, skeletal abnormalities with variable degree of osteopenia, frequent fractures, scoliosis, bowed long bones, vertebral collapse, and hyperextensible fingers. The disorder results from mutations in the GORAB—golgin, RAB6 interacting. This gene encodes a member of the golgin family, a group of coiled-coil proteins on golgin that maps to chromosome 1q24. The encoded protein has a function in the secretory pathway, was identified by terminal kinase-like protein, and thus, it may function in mitosis. Mutations in this gene have been associated with GO. Herein, we describe the clinical presentation of one young male patient from related Saudi parents. Mutations, a homozygous frameshift mutation (c.306dup p.(pro 103 Thrfs*20)). Interestingly, phenotypic variability was observed in this patient with GO features that were more atypical than the cases reported in the literature as he looks tall stature where most of the cases reported were short and arachnodactyly fingers which mimic other syndromes.

Phenotype from SAMD9 Mutation at 7p21.1 Appears Attenuated by Novel Compound Heterozygous Variants at RUNX2 and SALL1

Sterile α motif domain-containing protein 9 (SAMD9) is a regulatory protein centrally involved in cell proliferation and apoptosis. Mapped to 7p21.1, variants in SAMD9 have been reported in <50 pediatric cases worldwide, typically with early lethality. Germline gain-of-function SAMD9 variants are associated with MIRAGE syndrome (myelodysplasia, infection, restricted growth, adrenal hypoplasia, genital anomalies, and enteropathy). Spalt like transcription factor 1 (SALL1) is a zinc finger transcriptional repressor located at 16q12.1 where only two transcript variants in SALL1 are known. RUNX2 (6p21.1) encodes a nuclear protein with a Runt DNA-binding domain critical for osteoblastic differentiation, skeletal morphogenesis, and serves as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. RUNX2 and SALL1 are thus both “master regulators” of tissue organization and embryo development. Here, we describe exome sequencing and copy number variants in two previously unknown mutations—R824Q in SAMD9, and Q253H in SALL1. A multiexon 3′ terminal duplication of RUNX2 not previously encountered is also reported. This is the first known phenotype assessment for an intersection of all three variants in a healthy 46,XX adult. Focusing on developmental progress, ultrastructural renal anatomy, and selected reproductive aspects, we describe this unique genotype diagnosed incidentally during coronavirus disease 2019 (COVID-19) illness. Individually, disruption in SAMD9, RUNX2, or SALL1 would be expected to give a bleak prognosis. However, this variant convergence appears to dampen severe pathology perhaps by cross-gene silencing of effects normally deleterious when such changes occur alone.

Molecular Detection of blaOXA-type Carbapenemase Genes and Antimicrobial Resistance Patterns among Clinical Isolates of Acinetobacter baumannii

Acinetobacter baumannii is a bacterium found in most places, especially in clinics and hospitals, and an important agent of nosocomial infections. The presence of class D enzymes such as OXA-type carbapenemases in A. baumannii is proven to have a key function in resistance to carbapenem. The aim of the current study is to determine the blaOXA-type carbapenemase genes and antimicrobial resistance among clinically isolated samples of A. baumannii. We assessed 100 clinically isolated specimens of A. baumannii from patients in intensive care units of educational hospitals of Hamadan, West of Iran. The A. baumannii isolates' susceptibility to antibiotics was performed employing disk diffusion method. Multiplex polymerase chain reaction was used to identify the blaOXA-24-like , blaOXA-23-like , blaOXA-58-like , and blaOXA-51-like genes. The blaOXA-23-like , blaOXA-24-like , and blaOXA-58-like genes' prevalence were found to be 84, 58, and 3%, respectively. The highest coexistence of the genes was for blaOXA-51/23 (84%) followed by blaOXA-51/24-like (58%). The blaOXA-51/23- like pattern of genes is a sort of dominant gene in resistance in A. baumannii from Hamadan hospitals. The highest resistance to piperacillin (83%) and ciprofloxacin (81%) has been observed in positive isolates of blaOXA-23-like . The A. baumannii isolates with blaOXA-58-like genes did not show much resistance to antibiotics. Based on the results of the phylogenetic tree analysis, all isolates have shown a high degree of similarity. This study showed the high frequency of OXA-type carbapenemase genes among A. baumannii isolates from Hamadan hospitals, Iran. Thus, applying an appropriate strategy to limit the spreading of these strains and also performing new treatment regimens are necessary.

Epigenetic Approach to PTSD: In the Aspects of Rat Models

Posttraumatic stress disorder (PTSD) is a stress-related mental disorder and develops after exposure to life-threatening traumatic experiences. The risk factors of PTSD included genetic factors; alterations in hypothalamic–pituitary–adrenal (HPA) axis; neurotrophic, serotonergic, dopaminergic, and catecholaminergic systems; and a variety of environmental factors, such as war, accident, natural disaster, pandemic, physical, or sexual abuse, that cause stress or trauma in individuals. To be able to understand the molecular background of PTSD, rodent animal models are widely used by researchers. When looking for a solution for PTSD, it is important to consider preexisting genetic risk factors and physiological, molecular, and biochemical processes caused by trauma that may cause susceptibility to this disorder. In studies, it is reported that epigenetic mechanisms play important roles in the biological response affected by environmental factors, as well as the task of programming cell identity. In this article, we provided an overview of the role of epigenetic modifications in understanding the biology of PTSD. We also summarized the data from animal studies and their importance during the investigation of PTSD. This study shed light on the epigenetic background of stress and PTSD.

Investigation of Genetic Alterations in Congenital Heart Diseases in Prenatal Period

The prenatal diagnosis of congenital heart disease (CHD) is important because of mortality risk. The onset of CHD varies, and depending on the malformation type, the risk of aneuploidy is changed. To identify possible genetic alterations in CHD, G-banding, chromosomal microarray or if needed DNA mutation analysis and direct sequence analysis should be planned.In present study, to identify genetic alterations, cell culture, karyotype analysis, and single nucleotide polymorphism, array analyses were conducted on a total 950 samples. Interventional prenatal genetic examination was performed on 23 (2, 4%, 23/950) fetal CHD cases. Chromosomal abnormalities were detected in 5 out of 23 cases (21, 7%). Detected chromosomal abnormalities were 10q23.2 deletion, trisomy 18, 8p22.3-p23.2 deletion, 8q21.3-q24.3 duplication, 11q24.2q24.5 (9 Mb) deletion, and 8p22p12 (16.8 Mb) deletion. Our study highlights the importance of genetic testing in CHD.

A Pilot Study about Clinical Features of Aberrations Chromosome 22q

Objective A significant number of genetic variations have been identified in chromosome 22, using molecular genetic techniques. Various genomic disorders on chromosome 22, including cat's eye syndrome caused by extra copies of the proximal region of the 22q chromosome, are now well-defined.Our aim in the study was to show phenotypic variability associated with rearrangements of the 22q chromosomal region. Methods We focused our study on clinical aspects of these disorders, including genetic testing, genotype-phenotype correlation, and potential treatments. A total of 998 patients were referred for genetic analysis (Karyotyping, MLPA, array-CGH) during January 2015 to February 2020 because of intellectual deficiency, behavior issues, and/or multiple congenital abnormalities in several genetics departments. Informed consent was obtained from all the patients and/or their parents. Results 22q11.21 or 22q13.33 microdeletions and 22q11.22-q11.23 microduplication were identified in 31 patients out of referrals. The 22q aberrations were detected in 31/998 patients, giving a prevalence of 3.1%. In this study, 18 patients with 22q11.2 (LCR22A-H) deletion, three patients with 22q13.31 deletion, 9 patients with 22q11.2 duplication and one patient with 22q13.31 duplication were identified. We report on the clinical and molecular characterization of 31 individuals with distal deletions and duplications of chromosome 22q. Conclusions The current study demonstrated in the largest postnatal case series reporting the whole spectrum of atypical phenotypic and genotypic variations at 22q. We believe that when all the phenotypic differences are taken into account, various anomalies including developmental delay and intellectual disability might be considered as an indication to search for aberrations of 22q along with congenital heart diseases.

From Genetics to Epigenetics: Top 4 Aspects for Improved Vaccine Designs. Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines as Paradigmatic Examples

This literature review described the genetic and biochemical factors that may have been overlooked in the formulation of vaccines and that most likely underlie possible issues with mass vaccination.

Disease Progression and Mutation Pattern in a Large Cohort of LGMD R1/LGMD 2A Patients from India

Calpainopathy is caused by mutations in the CAPN3. There is only one clinical and genetic study of CAPN3 from India and none from South India. A total of 72 (male[M]:female [F] = 34:38) genetically confirmed probands from 72 independent families are included in this study. Consanguinity was present in 54.2%. The mean age of onset and duration of symptoms are 13.5 ± 6.4 and 6.3 ± 4.7 years, respectively. Positive family history occurred in 23.3%. The predominant initial symptoms were proximal lower limb weakness (52.1%) and toe walking (20.5%). At presentation, 97.2% had hip girdle weakness, 69.4% had scapular winging, and 58.3% had contractures. Follow-up was available in 76.4%, and 92.7% were ambulant at a mean age of 23.7 ± 7.6 years and duration of 4.5 years, remaining 7.3% became wheelchair-bound at 25.5 ± 5.7 years of age (mean duration = 13.5 ± 4.6), 4.1% were aged more than 40 years (duration range = 5–20). The majority remained ambulant 10 years after disease onset. Next-generation sequencing (NGS) detected 47 unique CAPN3 variants in 72 patients, out of which 19 are novel. Missense variants were most common occurring in 59.7% (homozygous = 29; Compound heterozygous = 14). In the remaining 29 patients (40.3%), at least one suspected loss of function variant was present. Common recurrent variants were c.2051–1G > T and c.2338G > C in 9.7%, c.1343G > A, c.802–9G > A, and c.1319G > A in 6.9% and c.1963delC in 5.5% of population. Large deletions were observed in 4.2%. Exon 10 mutations accounted for 12 patients (16.7%). Our study highlights the efficiency of NGS technology in screening and molecular diagnosis of limb-girdle muscular dystrophy with recessive form (LGMDR1) patients in India.

Toe Walking as the Initial Symptom of a Spinocerebellar Ataxia 13 in a Patient Presenting with a Mutation in the KCNC3 Gene

This article at hand described a 4-year-old patient who initially presented with the symptoms of toe walking. As part of the diagnostic process, the patient was genetically tested to find the cause of the gait anomaly. The genetic test found a mutation in the KCNC3 gene. The variant c.1268G > A; p.Arg423His was found in a heterozygotic state. This variant is frequently described as a cause for spinocerebellar ataxia type 13 (SCA13) in the literature. Apart from toe walking as the most pronounced symptom, the patient displayed an instable gait with frequent falls and delayed speech development. The genetic test to determine the cause of the gait anomaly successfully diagnosed the patient with a previously undiscovered SCA13 and subsequently enabled the recommendation of personalized further treatment.

A New Perspective of COVID-19 Infection: An Epigenetics Point of View

Coronavirus disease 2019 (COVID-2019) started in Wuhan, China, in December 2019. Angiotensin-converting enzyme 2 (ACE2) receptor was one of the most important genes related to the entrance of the virus to the host. Until now, several variations have been identified in ACE2 and related transmembrane protease serine 2. Epigenetic modifications not only play an important role during the maintenance of genome and cellular homoeostasis but also for the etiopathophysiology of the virus infection. Studies showed methylation of ACE2 was changed to depend on host and age of the host during the viral infection.In this study, we provide an epigenetics point of view to the coronavirus infection. We highlight the importance of epigenetic modifications during viral replication and infection and their interaction with COVID-19 susceptibility and host viral response.