Year 2023, Volume 6 - Issue 2

Not available

Background: The term "Syndactyly" referred to an inherited deformity of the hand or foot marked by persistence of the webbing between adjacent digits that are more or less completely attached and mostly inherited in an autosomal dominant manner. Pathogenic variants in the HOXD13 (Homeobox D13) gene, located on chromosome 2q31.1, have been associated with syndactyly type 5, brachydactyly type D, E and synpolydactyly type 1 phenotypes. Objectives: A Pakistani inbreed was recruited from the remote area of the country was added in the study and aimed to clinically and genetically characterize the syndactyly as marked abnormal feature observed. Methodology: Whole exome sequencing coupled with Sanger sequencing was carried out to uncover the disease associated variant/s followed by 3D protein modeling to check variant related effect on protein level. Results: WES data analysis revealed a novel-HOXD13 gene missense variant (c.969G>T; p.Trp323Cys) that might explain the disease phenogenesis. 3D protein modeling of the normal and mutant protein predicated high level changes that might compromise the ultimate function of the protein. Conclusion: Our findings extend the mutation spectrum of HOXD13 gene and also provided additional evidence that HOXD13 play an important role in limbs development.

Abstract Purpose: The purpose of this paper is to construct and validate the immune-related prognostic signature in lung squamous cell carcinoma through integrated bioinformatics analysis. Methods: We constructed an optimized prognostic risk model consisting of five PIR-lncRNAs (AC107884.1, LCMT1-AS1, AL163051.1, AC005730.3 and LINC02635). We then performed survival analysis and independent prognostic analysis on the prognostic risk model to assess and validate the prognostic value of the model. Further, we performed differential analysis of immune cell infiltration between high- and low-risk patients in the model. Results: In this article, we obtained 546 differentially expressed genes and 21 immune-related genes, identified 654 immune-related lncRNAs (IR-lncRNAs) by co-expression network analysis, and identified 18 prognostic IR-lncRNAs (PIR-lncRNAs) by univariate Cox analysis. Through the analysis of immune escape and immunotherapy, we verified that the effect of immunotherapy in high-risk group patients may be lower. Conclusion: Our findings elucidate the intrinsic molecular biological link between the pathogenic genes of lung squamous cell carcinoma (LUSC) and immune cells, which has important exploration and reference significance for the precise and potential immunotherapy of LUSC patients, especially for high-risk patients.

Genetic skeletal disorders (GSDs) are heritably and clinically varied class of bone and cartilage anomalies, characterized by irregular growth/development of the skeleton. They are rare, but their cases may be upraised with endogamy as it increases homozygosity. Pakistan has highest rate (55-60%) of consanguinity, which is highly detrimental to health. Still, Pakistan has no reliable data (geographical prevalence, clinical and epidemiological data) associated with GSDs and other rare genetic disorders. Unfortunately, due to the lack of adequate clinical/diagnostic resources and genetic knowledge, the suspected cases of genetic disorders are misdiagnosed and hence mistreated, thus, casing psycho-socio-economic problems. The present study reviewed current literature, published in several internet data-bases included the Nosology of Genetic Skeletal Disorders: (2023 Revision)" from Pakistan. GSDs such as Acromesomelic dysplasia, Mucopolysaccharidosis, Polydactyly, Synpolydactyly and Split hand/Split foot malformation were reported in several families and have a 55.04% of all the reported GSDs from Pakistan. Till-date, in the literature 72 different mutated genes has been reported from Pakistani community. This review will help clinicians and researchers in understanding, diagnosis and management of GSDs and will offer a descriptive of approach to carry out fruitful molecular genetic research in genetically vulnerable and low resource regions. Moreover, it will also speed up the possible therapy development and may insist the stakeholders to establish a multi-level network to find a path towards the healthcare challenges of GSDs from Pakistan.

Nystagmus is an involuntary, periodic eye movement caused by a slow drift of fixation of either jerk, pendular, or rotatory form. The clinical and molecular assessment of nystagmus can provide crucial elements for a state-of-the-art differential diagnosis. Herewith, we provide a comprehensive overview of idiopathic infantile nystagmus, one of the most common forms of infantile nystagmus that is usually reached out by exclusion of a variety of underlying causes and considered as one of the main leading causes of visual debleating disorders in early childhood.

Background: Infantile onset progressive leukoencephalopathy with or without deafness is an autosomal recessive neurodegenerative disorder with variable clinical presentation, manifesting in infancy or early childhood. This disorders is one of KARS1 gene mutation spectrum that results mostly from compound heterozygous mutations rather than homozygous mutations, resulting in a dysfunctional mitochondrial enzyme. Case presentation: We report our 4-year-old Saudi boy of non-consanguineous parents, with a compound heterozygous mutation in KARS1 gene presenting clinically with speech delay, bilateral sensonural hearing loss, unilateral progressive hemiparesis, iron deficiency anemia and lytic bone lesions. Conclusion: KARS1 mutation has a heterogenous phenotypic presentation, and variable clinical severity. We report a new clinical feature of lytic bone lesions which could potentially expand the phenotype of this genetic disorder spectrum. Early recognition of the clinical presentation is warranted to facilitate diagnosis, prognosis and appropriate family counseling.

Background: Autosomal recessive developmental and epileptic encephalopathy type 28 (DEE28) is a rare genetic disorder that affects children in the early months of life. It is proved to be caused by a pathogenic variance in WW domain-containing oxidoreductase (WWOX) gene. Case presentation: Here, we report a 5-year-old male patient with autosomal recessive DEE28. Whole exome sequencing (WES) test was conducted and resulted in a pathogenic result on WWOX gene pathogenic variant. To our knowledge, these are the first cases reported in Oman. Conclusion: For patients with DEE28, it is essential to take the full family history and genetic workup to assist in the diagnosis. In the future, gene therapy – which is currently being investigated - may help those patients to have a good quality of life and improve the prognosis of the disease.

Background TANGO2 depletion was found to cause clinically recognizable multi-organ involvement disorder in pediatrics with episodic muscle weakness recurrent rhabdomyolysis, intellectual disability, metabolic encephalomyopathic crises and cardiac arrhythmia. TANGO2 deficiency is also referred to as "metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration" (MECRCN) in OMIM. * 616830 Case presentation We report a case of a 4-year-old Saudi boy from a consanguineous Saudi family with two uncles deceased at 3 year of age with recurrent muscle weakness and hyperammonemia of unknown cause .Patient in last attack progressed to severe metabolic encephalomyopathic crisis that required assisted ventilation for 4 months, complicated with life threatening cardiac tachyarrhythmia. Laboratory findings of hypoglycemia, mild hyperammonemia , severely elevated plasma Creatine Kinase, myoglobinuria , lactic acidosis and increased TSH concentration indicating hypothyroidism have been documented. The clinical profile was highly suggestive of TANGO2-realted disorder. Direct DNA sequence analysis of the entire coding regions of TANGO2 gene identified a novel homozygous deletion for three nucleotides in exon 2 (c.11_13delTCT) resulting in amino acid deletion (phenylalanine) at position 5. Conclusion This report illustrates the importance of collating clinical data and keeping a high index of suspicion in order to reach to the diagnosis.

Background: Piebaldism (OMIM #172800) is a rare autosomal dominant genodermatosis characterized by congenital poliosis and stable patches of leucoderma. Piebaldism is caused by mutations in the KIT and SNAI2 genes. The most common mutations are detected in the KIT gene. Case presentation: A 5-year-old boy, who was followed-up for aphakic glaucoma after congenital cataract surgery, was consulted to the medical genetics and dermatology departments due to premature graying of the hair, white forelock in the frontal region of the scalp, whitening in the inner part of the eyebrows and eyelashes and patchy leukoderma with hyperpigmented islands inside on the extremities and trunk. DNA sequencing revealed a heterozygous missense c.1861G>A mutation in the KIT gene. Mutation was evaluated using in silico 3D-structure analysis and bioinformatics tools Conclusion: KIT gene has a critical role in melanoblast migration, proliferation, differentiation and survival and molecular dynamics simulation and modeling proved that this variant inhibits the migration of melanoblasts and melanocytes by reducing the enzymatic activity of the KIT protein.

Background: Ellis-van Creveld syndrome (EVC) causes chondral and ectodermal abnormalities. Although the precise prevalence is still unknown, the Amish group in the United States most frequently reports this uncommon sickness. Case presentation: The reported case was of a 2-year-old female patient presented with dysmorphic facial and digital features, polydactyly, dwarfism, inability to walk normally, and multiple cardiac abnormalities. On examination, the patient's growth parameters were below the 5th percentile, with a weight of 10 kg, height of 72 cm, and head circumference of 45 cm (10th percentile). The patient had sparse, thin hair with bi-temporal narrowing and frontal bossing. The patient was advised to undergo surgery, which included AV canal repair, atrial septal defect closure, VSD closure, Mitral and tricuspid valve cleft closure, and left SVC tunneling to the right atrium. One week after the operation, the patient developed sudden bilateral visual impairment, with no hemorrhage or space-occupying lesions. The patient was discharged on day 15 after surgery, and although stable, the visual impairment remained. Conclusion: This case is believed to be one of the first cases in Palestine, as this disease is very rare worldwide. The outcomes of the condition are thought to be well predicted by prenatal discoveries.

The inner mitochondrial membrane peptidase subunit 2-like protein, the IMMP2L gene in 7q31.1, have been associated with different neurodevelopmental disorders, including autism spectrum disorders, attention deficit/hyperactivity disorder and Gilles de la Tourette's syndrome (GTS). Since the use of comparative genomic hybridization as essential tool in the diagnostic workup of neurodevelopmental disorders, recurrent microdeletions CNV's were identified in IMMP2L gene. We report here a 3 years old girl presenting since early life with complex motor tics, developmental delay, and other various cognitive/behavioral disturbances. Array CGH analysis showed a 331 Kb de novo pathogenic heterozygous deletion at 7q31.1 into the IMMP2L gene, involving exons 1 to 3. We discuss the functions of IMMP2L gene suggesting that his disruption may act as high-risk factor for neurodevelopmental disorders and movement disorders.