Genetic Disorders - Science topic

Objective: Premarital, unfortunately, does not cover all possible genetic diseases, such as deafness and congenital heart diseases, diabetes mellitus, and hypertension, nor does it cover unknown genetic mutations that may cause severe defects in subsequent generations. However, the Saudi population has limited knowledge regarding premarital screen...

Introduction The analysis of signaling pathways is a cornerstone in clarifying the biological mechanisms involved in complex genetic disorders. These pathways have intricate topologies, and the existing methods that are used for the interpretation of these pathways, remain limited. We have therefore developed the Adaptable Large-Scale Causal Analys...

IntroductionAutism spectrum disorder (ASD) is a highly heterogeneous and complex disorder with co-occurring disorders commonplace. This presents tremendous diagnostic challenges given the phenotypic overlap between autism and other diagnoses, including social anxiety, as well as variance in specific genetic disorders like fragile X syndrome (FXS)....

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder associated with increased immune activity and severe, progressive heterotopic ossification. We previously described a cohort of 32 patients with FOP who were either exposed to SARS-CoV-2 or received a COVID-19 vaccine ¹ and showed that these patients did not develop heterotopic...

H63D Syndrome Type-2 is a complex genetic disorder with diverse manifestations, including erratic iron metabolism, micro-inflammatory cascades, neuropsychiatric issues, organ damage, and other rare multi-faceted symptoms. A comprehensive understanding of the pathophysiology underlying this condition is essential for accurate diagnosis, appropriate...

Heterotopic ossification (HO) is the abnormal growth of bone in soft connective tissues that occurs as a frequent complication in individuals with traumatic brain injury (TBI) and in rare genetic disorders. Therefore, understanding the mechanisms behind ectopic bone formation in response to TBI is likely to have a significant impact on identificati...

Krabbe disease (KD) is a genetic disorder caused by the absence of the galactosylceramidase (GALC) functional enzyme. No cure is currently available. Here, we investigate the mechanotransduction process in primary fibroblasts collected from the twitcher mouse, a natural KD murine model. Thanks to mechanotransduction, cells can sense their environme...

Nuclear speckles are small, membrane-less organelles that reside within the nucleus. Nuclear speckles serve as a regulatory hub coordinating complex RNA metabolism steps including gene transcription, pre-mRNA splicing, RNA modifications, and mRNA nuclear export. Reflecting the importance of proper nuclear speckle function in regulating normal human...

Acroosteolysis (AO) is a rare condition characterized by resorption of the distal phalanges of the fingers and/or toes. It can be familial, idiopathic (IAO), occupational, or secondary. Other authors suggest a classification into primary (genetic disorders, lysosomal storage disorders) or secondary AO. Various skin and nail changes have been report...

Impaired glycosaminoglycans (GAGs) catabolism may lead to a cluster of rare metabolic and genetic disorders called mucopolysaccharidoses (MPSs). Each subtype is caused by the deficiency of one of the lysosomal hydrolases normally degrading GAGs. Affected tissues accumulate undegraded GAGs in cell lysosomes and in the extracellular matrix, thus lead...

Cowden syndrome is a rare autosomal dominant genetic disorder characterized by a germline mutation in the phosphatase and tensin homolog gene, leading to multiple hamartomas, neurodevelopmental disorders, and an increased lifetime risk of multiple cancers. Malignancy is the most common cause of mortality in Cowden syndrome, with breast cancer being...

Small interference RNA (siRNA) is a double-stranded RNA of 21~25 nucleotides. siRNA functions using a natural phenomenon known as RNA interference (RNAi), a gene silencing mechanism. Hypothetically, siRNA can target and regulate the expression of any disease-related gene in a sequence-specific manner. In 1993, this mechanism was noticed in a nemato...

Dantrolene is an intra-cellularly acting skeletal muscle relaxant used for the treatment of the rare genetic disorder, malignant hyperthermia (MH). In most cases, MH susceptibility is caused by dysfunction of the skeletal ryanodine receptor (RyR1) harboring one of nearly 230 single-point MH mutations. The therapeutic effect of dantrolene is the res...

Dantrolene is an intra-cellularly acting skeletal muscle relaxant used for the treatment of the rare genetic disorder, malignant hyperthermia (MH). In most cases, MH susceptibility is caused by dysfunction of the skeletal ryanodine receptor (RyR1) harboring one of nearly 230 single-point MH mutations. The therapeutic effect of dantrolene is the res...

Sarcoma is a type of cancer that affects the connective tissues of the body, including bone, cartilage, muscle, fat, and blood vessels. It is a relatively rare type of cancer, accounting for less than 1% of all adult cancers, but it can be particularly aggressive and difficult to treat. In this article, we will explore some of the basics of sarcoma...

Several growth-related disorders in the modern poultry industry are complex, recurring, and challenging chicken performance hazards. These kinds of non-infectious disorders have led to negative consequences in health, mobility, and performance conditions in chickens. Despite their significance and recurrence in the modern poultry, there is no compr...

Vaginal atresia is seen in genetic disorders such as Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome, which can cause significant sexual dysfunction. Current treatments include surgical reconstruction or mechanical dilation of the vaginal canal. Mechanical dilation requires patients to be highly motivated and compliant while surgical reconstruction...

Congenital hyperinsulinism, a rare genetic disorder characterized by excess insulin secretion even during hypoglycemic episodes, has two histological subtypes; diffuse and focal. Genotypes denote which of the two subtypes presents, and this is the first case being reported in Nigeria. The aims of this study were to report the first case of genetica...

Hereditary tyrosinemia type 1 (HT1) is a genetic disorder of the tyrosine degradation pathway (TIMD) with unmet therapeutic needs. HT1 patients are unable to fully break down the amino acid tyrosine due to a deficient fumarylacetoacetate hydrolase (FAH) enzyme and, therefore, accumulate toxic tyrosine intermediates. If left untreated, they experien...

Introduction: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder affecting several organs, including skin. We sought to assess the real-world effectiveness and safety of a topical sirolimus 0.2% gel treatment for TSC-related cutaneous manifestations. Methods: We conducted an interim analysis of postmarketing surveilla...

Nonlesional focal epilepsies (nlFE) represent a heterogenous group of syndromes. They encompass self-limited focal epilepsies of childhood and youth, rare focal, familial epilepsies, epilepsies associated with brain somatic variants, and to a large extent nonfamilial epilepsies that have a complex genetic or unknown background. Genetic testing shou...

Background Haemophilia is an X-linked recessive genetic disorder characterised by bleeding within soft tissue and joints. The ankle is disproportionally affected by haemarthropathy when compared to the elbows and knees; reported as the most affected joints in patients with haemophilia. Despite advances in treatment, patients still report ongoing pa...

The occurrence of both melanoma and glioma was first suggested by the observation of a familial association between these conditions, which was later confirmed by the description of the melanoma–astrocytoma syndrome, an extremely rare, inherited affliction in which people have an increased risk of developing melanoma and nervous system tumors. Taki...

Skeletal dysplasias collectively affect a large number of patients worldwide. The majority of these disorders cause growth anomalies. Hence, assessing skeletal maturity via determining the bone age (BA) is one of the most valuable tools for their diagnoses. Moreover, consecutive BA assessments are crucial for monitoring the pediatric growth of pati...

Background and aim: Myotonic dystrophy (DM) is a genetic disorder determined by an amplified trinucleotide CTG repeat in the untranslated region of the DMPK gene on chromosome 19q13.3. The incidence of the congenital form is 1 in 47619 live births and the mortality in the neonatal period is up to 40%. Methods: We report a case of congenital DM (CDM...

Bannayan-Zonana syndrome (BRRS) is a rare genetic disorder characterized by macrocephaly, numerous soft tissue and visceral hamartomas, and lipomas. Because of the risk of fatal bleeding and visceral neoplasia in adulthood, recognizing this disease is critical. We reported a new pediatric case of BRRS in an 18-month-old female infant with lipomas,...

Pyridoxine‐dependent epilepsy (PDE) was historically defined by a dramatic clinical response to a trial of pyridoxine and the re‐emergence of seizures after withdrawal of pyridoxine. Research conducted over the last seven decades has revealed that the phenotype of PDE results from multiple genetic disorders, and the most common disorder, PDE‐ALDH7A...

Phelan-McDermid syndrome (PMS) is a rare genetic disorder typically caused by loss or disruption of the distal long arm of chromosome 22. Children with PMS exhibit severe to profound communication deficits, and the majority meet the criteria for Autism Spectrum Disorder (ASD). To date, no language or communication intervention studies focused on ch...

Like many other Arab countries, the United Arab Emirates (UAE) has a relatively high prevalence of genetic disorders. Here we present the first review and analysis of all genetic disorders and gene variants reported in Emirati nationals and hosted on the Catalogue for Transmission Genetics in Arabs (CTGA), an open-access database hosting bibliograp...

Kartagener’s syndrome (KS) is a genetic disorder and a subgroup of primary ciliary dyskinesia characterized by situs inversus, chronic sinusitis and bronchiectasis. Patients with KS can develop severe bronchiectasis with end-stage lung disease due to recurrent pulmonary infections. Lung transplantation is a treatment option with good outcomes repor...

Genetic disorder is considered as one of the major challenges faced by Medical Sciences as it is inherited by humans from one generation to another. With an increasing number of natives of the World at a higher rate, it causes a major impact on information society socially and economically during their lifetime. The citizens of Pakistan and Indian...

Bernese mountain dogs are a large dog breed formed in the early 1900s in Switzerland. While originally farm dogs that were used for pulling carts, guarding, and driving cattle, today they are considered multi-purpose companion and family dogs. The breed is predisposed to several complex diseases, such as histiocytic sarcoma, degenerative myelopathy...

Epidermolysis Bullosa (EB) is a group of rare genetic disorders that compromise the structural integrity of the skin such that blisters and subsequent erosions occur after minor trauma. While primary genetic risk of all subforms of EB adhere to Mendelian patterns of inheritance, their clinical presentations and severities can vary greatly, implying...

Barth Syndrome is a rare X-linked genetic disorder caused by mutations in the TAFAZZIN gene. We recently demonstrated that tafazzin (Taz) protein deficiency in murine mesenchymal stems (MSCs) reduces immune function of activated wild type (WT) B lymphocytes. Interleukin-10 (IL-10) is a key anti-inflammatory cytokine capable of exerting immunosuppre...

Down’s syndrome or trisomy 21 is a genetic disorder caused by presence of all or a part of a third copy of chromosome 21. Keratoconus occurs in up to 15% of the adult population with Down’s syndrome. There is a close consortium between trisomy 21 and keratoconus (a conical ectatic protrusion of the cornea), and children with Down’s syndrome are als...

Background: Henoch-Schönlein purpura (HSP) is a common form of immunological vasculitis in children. Hemophilia A is a genetic disorder and characterized by spontaneous hemorrhage or prolonged bleeding due to factor VIII deficiency. Both diseases increase the risk of bleeding, but they have different mechanisms. How should we treat patients with b...

Leukoencephalopathy with calcifications and cysts is a rare autosomal recessive genetic disorder neuroradiologically characterized by intracranial calcification, cerebral white matter disease, and multiple cysts. Although SNORD118 genes have recently been identified as a cause of this disorder, its clinical course varies for each patient. We report...

Birt-Hogg-Dube syndrome is an extremely rare genetic disorder featuring multiple lung cyst or bulla which lead to recurrent spontaneous pneumothorax. Laparoscopic cholecystectomy poses a significant challenge in such cases from anesthetic point of view. Thoracic segmental spinal anesthesia (TSS) is a relatively new and beneficial alternative to gen...

Background: Restricted and repetitive behaviors (RRBs) are a broad class of behaviors characterized by frequent action repetition and intense preference for sameness. Research has predominantly focused on RRBs in diagnosed clinical groups, particularly in autism spectrum disorder and genetic disorders. Using a transdiagnostic approach, the current...

Introduction: Holt–Oram syndrome (HOS) is a rare genetic disorder characterized by upper limb abnormalities, congenital heart defects, and/or conduction abnormalities. Sequence alteration of T-box transcription factor 5 (TBX5) is correlated with the incidence of HOS. Case description: We present the case of a 24-year-old female with upper limb alte...

Introduction Heterozygous pathogenic and likely pathogenic sequence variants in the RUNX1 (Runt-related Transcription Factor 1) gene are a common genetic cause of decreased platelet count and/or platelet dysfunction and an increased risk of developing myelodysplasia and acute myeloid leukemia. The majority of causative variants are substitutions, w...

Turner Syndrome (TS) is a genetic disorder caused by total or partial loss of an X chromosome. The isochromosome X (i(X)) is a known variant of TS, however, double i(X) is a very rare variant, reported very few times in the literature. We report on a rare case of TS with double i(X). This is an 11-year-old female patient , addressed to the medical...

Cystic fibrosis is an autosomal recessive genetic disorder that damages the exocrine function of the body, resulting in alterations of multiple organs. In the respiratory system, it is known to cause bronchiectasis, recurrent bronchitis, and pneumonia; however, to the best of our knowledge, there are no reported cases of pulmonary arteriovenous mal...

Introduction: Ring chromosome 14 syndrome, or r(14), is a rare genetic disorder characterized by distinctive facial features, intractable epilepsy, delayed development, intellectual disability, and autism spectrum disorder. With less than 100 documented cases worldwide, the disease is not well known or fully studied. Furthermore, the literature of...

Structural Maintenance of Chromosomes Flexible Hinge Domain Containing 1 (SMCHD1) is a non-canonical member of the structural maintenance of chromosomes (SMC) protein family involved in the regulation of chromatin structure, epigenetic regulation and transcription. Mutations in SMCHD1 cause facioscapulohumeral muscular dystrophy type 2 (FSHD2), a r...

Background Waardenburg syndrome (WS) is a genetic disorder that affects skin, hair, and iris pigmentation, and causes sensorineural deafness. The syndrome is classified into four types (WS1, WS2, WS3, and WS4), each with different clinical phenotypes and underlying genetic causes. The aim of this study is to identify the pathogenic mutation in a Ch...

Introduction: Steinert's disease is a rare genetic disorder characterized by progressive myotonia and multi-organ damage. It is associated with respiratory and cardiological complications often leading patients to exitus. These conditions are also traditional risk factors for severe COVID-19. SARS-CoV-2 has affected people with chronic diseases, b...

Cystic fibrosis is a genetic disorder caused by a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene defect. Many across the globe suffer the debilitating symptoms. The aim of this commentary is to briefly cover various aspects related to the disease in the Arab world and then in Qatar.

Kyphoscoliotic Ehlers–Danlos syndrome (kEDS) is a rare genetic disorder combining congenital hypotonia, congenital/early onset and progressive kyphoscoliosis, and generalized joint hypermobility. Vascular fragility is another characteristic of the disease rarely described. We report a severe case of kEDS‐PLOD1 with several vascular complications le...

(1) Background: Alpha (α)-thalassaemia is a genetic disorder that affects 5% of the world population. Deletional or nondeletional mutations of one or both HBA1 and HBA2 on chromosome 16 will result in reduced production of α-globin chains, a component of haemoglobin (Hb) that is required for the formation of red blood cells (RBCs). This study aimed...

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder and the most debilitating condition of heterotopic ossification in humans. Misdiagnosis is common and they suffer from complications of incorrect diagnosis and subsequent inappropriate treatment hence, to create awareness, we are reporting a genetically confirmed case of FOP. A...

Sickle cell disease (SCD) is a common genetic disorder in Africa. Some ongoing work in SCD research includes the analysis and comparisons of variation in phenotypic presentations and disease outcomes with the genotypic signatures. This has contributed to the observed growth of molecular and genetic data in SCD. However, while the "omics" data conti...

Background: The oral cavity is an anatomically part of the body that has complex tissues and structures and is covered by soft, moist, and flexible nonkeratinized mucosa for mobility. In some individuals, normal variations can be found, one of which is the White Sponge Nevus (WSN). These lesions are usually in the form of patches of white plaque...

Ataxia telangiectasia is rare inherited disorder characterized by progressive, neurodegenerative, variable immunodeficiency, celebral ataxia, ocular and cutaneous telangiectasia. They are prone for sinopulmonary infection also at risk of cancer development. Hallmark of disease is ataxia and telangiectasia. Incidence is 1 in 1,00,000 live births. 10...

Aicardi-Goutières syndrome (AGS) is a rare genetic disorder involving the central nervous system and autoimmune abnormalities, leading to severe intellectual and physical disability with poor prognosis. AGS has a phenotype similar to intrauterine viral infection, which often leads to delays in genetic counseling. In this study, we report a case wit...

Purpose. Malignant hyperthermia (MH) is a rare genetic disorder but one of the most severe complications of general anesthesia. The mortality rate of MH has dropped from 70% in the 1960s to 15% because of dantrolene, the only currently accepted specific treatment for MH. In this study, we retrospectively identified the optimal dantrolene administra...

Introduction: Sickle cell disease is a genetic disorder that frequently presents with vaso-occlusive crisis (VOC). Most patients with sickle cell disease in Qatar are Muslims; hence, they practice intermittent fasting during the holy month of Ramadan. However, there is a paucity of literature describing the effect of intermittent fasting on the oc...

Prader–Willi syndrome (PWS) is a complex genetic disorder with three PWS molecular genetic classes and presents as severe hypotonia, failure to thrive, hypogonadism/hypogenitalism and developmental delay during infancy. Hyperphagia, obesity, learning and behavioral problems, short stature with growth and other hormone deficiencies are identified du...

Mucopolysaccharidoses (MPS) are rare genetic disorders belonging to the lysosomal storage diseases. They are caused by mutations in genes encoding lysosomal enzymes responsible for degrading glycosaminoglycans (GAGs). As a result, GAGs accumulate in lysosomes, leading to impairment of cells, organs and, consequently, the entire body. Many of the th...

Schaaf-Yang Syndrome (SYS) is a genetic disorder caused by truncating pathogenic variants in the paternal allele of the maternally imprinted, paternally expressed gene MAGEL2 and is characterized by genital hypoplasia, neonatal hypotonia, developmental delay, intellectual disability, autism spectrum disorder (ASD), and other features. In this study...

APECED syndrome is an inherited genetic disorder that affects many organs in the body. Other features of the APECED immune system include an attack on the hormone-producing glandular network (endocrine system). The second characteristic of this disorder is hypoparathyroidism, which is a dysfunction of the parathyroid glands. APECED syndrome is caus...

Pyelectasis, also known as renal pelvic dilatation or hydronephrosis, is frequently found on fetal ultrasound. This study correlated prenatally-detected, moderate pyelectasis with postnatal outcomes. This retrospective, observational study was conducted at a tertiary medical center in Israel. The study group consisted of 54 fetuses with prenatal di...

Solid lipid nanoparticles (SLNs), the spher-oidal-shaped, colloids state lipophilic-natured, innovative nanoscale particulate materials, are being concurrently prepared by the quality-by-design approach for cellular and sub-cellular delivery of drugs and other payloads with facilitated physicochemical characteristics for targeted delivery. The deli...

Introduction: Gorlin syndrome (GS) or nevoid basal cell carcinoma syndrome (NBCCS) is a rare genetic disorder characterised by development of multiple basal cell carcinomas (BCCs) at a young age. NBCCS occurs because of mutations in the PTCH1 gene, which functions as a tumour suppressor gene. Patients with GS can have varied manifestations, both cu...

The scope of this chapter is to provide insights into the classification based on the significant factors causing dry eye. The etiological causes of dry eye have been classified broadly into two primary arms. The first arm, aqueous deficient dry eye (ADDE), illustrates malfunction of normal lacrimal secretion causing tear hyposecretion. ADDE is sub...

Arrhythmogenic cardiomyopathy (ACM) is largely an autosomal dominant genetic disorder manifesting fibrofatty infiltration and ventricular arrhythmia with predominantly right ventricular involvement. ACM is one of the major conditions associated with an increased risk of sudden cardiac death, most notably in young individuals and athletes. ACM has s...

Motor dysfunctions in patients with Down Syndrome (DS) result in poor locomotion and an altered gait phenotype, characterized by compromised stability management and frequent bilateral asymmetries. Directing ground reaction forces to a point above the center of mass, referred to as the virtual pivot point (VPP), is one means of maintaining stabilit...

Holoprosencephaly (HPE) is a rare birth defect that occurs during the first few weeks of pregnancy. It results from a disturbance in the usual signaling pathways required for separation of the embryonic prosencephalon into 2 separate cerebral hemispheres. Classically four subtypes have been recognized: alobar, semilobar, lobar, and middle interhemi...

The fruit fly—i.e., Drosophila melanogaster—has proven to be a very useful model for the understanding of basic physiological processes, such as development or ageing. The availability of straightforward genetic tools that can be used to produce engineered individuals makes this model extremely interesting for the understanding of the mechanisms un...

Down syndrome (DS) is a genetic disorder with an abnormality in chromosome 21. By the age of 40, most patients with DS exhibit hallmarks of Alzheimer's disease (AD), manifesting as the accumulation of plaques and tangles in their brains. Our understanding of Alzheimer's and DS neuropathology at the molecular level before the onset of clinical patho...

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication along with repetitive stereotypic behaviors. Currently, there are no specific biomarkers for diagnostic screening or treatments available for autistic patients. Numerous genetic disorders are associated with h...

Adeno-associated Viral vectors (AAVs) have been successful exploited in gene therapy applications for the treatment of several genetic disorders. AAV is considered an episomal vector but it has been shown to integrate within the host-cell genome following generation of double-strand DNA breaks or nicks. While AAV integration raises some safety conc...