Whole exome sequencing of a novel homozygous missense variant in PALB2 gene leading to Fanconi anaemia complementation group.

Partner and localiser of BRCA2 (PALB2), also known as FANCN, is a key tumour suppressor gene in maintaining genome integrity. Monoallelic mutations of PALB2 are associated with breast and overian cancers, while bi-allelic mutations cause Fanconi anaemia (FA). In the present study, whole exome sequencing (WES) identified a novel homozygous missense variant, NM_024675.3: c.3296C>G (p.Thr1099Arg) in PALB2 gene (OMIM: 610355) that caused FA with mild pulmonary valve stenosis and dysmorphic and atypical features, including lymphangiectasia, non-immune hydrops fetalis and right-sided pleural effusion in a preterm female baby. WES results were further validated by Sanger sequencing. WES improves the screening and detection of novel and causative genetic variants to improve management of disease. To the best of our knowledge, the present study is the first reported FA case in a Saudi family with phenotypic atypical FA features. The results support the role of PALB2 gene and pathogenic variants that may cause clinical presentation of FA. Furthermore, the present results may establish a disease database, providing a groundwork for understanding the key genomic regions to control diseases resulting from consanguinity.

Phenotypic Classification of Eye Colour and Developmental Validation of the Irisplex System on Population Living in Malakand Division, Pakistan.

The core objective of forensic DNA typing is developing DNA profiles from biological evidence for personal identification. The present study was designed to check the validation of the IrisPlex system and the Prevalence of eye colour in the Pakhtoon population residing within the Malakand Division. METHODS: Eye colour digital photographs and buccal swab samples of 893 individuals of different age groups were collected. Multiplexed SNaPshot single base extension chemistry was used, and the genotypic results were analysed. Snapshot data were used for eye colour prediction through the IrisPlex and FROG-kb tool. RESULTS: The results of the present study found brown eye colour to be the most prevalent eye colour in comparison to intermediate and blue coloured. Overall, individuals with brown-coloured eyes possess CT (46.84%) and TT (53.16%) genotypes. Blue eye-coloured individuals are solely of the CC genotype, while individuals of intermediate eye colour carry CT (45.15%) and CC (53.85%) genotypes in rs12913832 SNP in the HERC2 gene. It was also revealed that brown-coloured eyes individuals were dominant among all age groups followed by intermediate and blue. Statistical analysis between particular variables and eye colour showed a significant p-value (<0.05) for rs16891982 SNP in SLC45A2 gene, rs12913832 SNP in HERC2 gene, rs1393350 SNP in SLC45A2, districts and gender. The rest of the SNPs were non-significant with eye colour, respectively. The rs12896399 SNP and SNP rs1800407 were found significant with rs16891982 SNP. The result also demonstrated that the study group differs from the world population based on eye colour. The two eye colour prediction results were compared, and it was discovered that IrisPlex and FROG-Kb had similar higher prediction ratios for Brown and Blue eye colour. CONCLUSIONS: The results of the current study revealed brown eye colour to be the most prevalent amongst members of the local population of Pakhtoon ethnicity in the Malakand Division of northern Pakistan. A set of contemporary human DNA samples with known phenotypes are used in this research to evaluate the custom panel's prediction accuracy. With the aid of this forensic test, DNA typing can be supplemented with details about the appearance of the person from whom the sample was taken in cases involving missing persons, ancient human remains, and trace samples. This study may be helpful for future population genetics and forensics studies.

Guillain-Barré Syndrome Following the BNT162b2 mRNA COVID-19 Vaccine.

PURPOSE: The onset of the COVID-19 (SARS-CoV-2) pandemic in December 2019 created the need for multiple scientific research activities and clinical trials in an attempt to find solutions to mitigate the impact of the virus. One of the important tools to combat the virus is the development of vaccination programs. All types of vaccines have been associated with a mild to severe risk of neurological adverse events. One of these severe adverse events is Guillain-Barré syndrome. CASE REPORT: Here, we describe a case of Guillain-Barré syndrome after the first dose of the BNT162b2 mRNA COVID-19 vaccine and review the literature to increase the current knowledge regarding this complication. CONCLUSION: Guillain-Barré syndrome after COVID-19 vaccination is responsive to treatment. The benefits of administering the vaccine outweigh the risks. Due to the negative impact of COVID-19, it is essential to recognize the development of neurological complications that are potentially associated with vaccination, including Guillain-Barré syndrome.

Automated pupillometry in space neuroscience.

Modern pupillometers are automated, thereby providing an objective, accurate, and reliable evaluation of various aspects of the pupillary light reflex at precision levels that were previously unobtainable. There are many gaps in knowledge regarding pupil size and pupillary light reflex in nervous system changes related to space travel given the previous lack of a precise method to quantitatively measure it. Automated pupillometry has not been used previously in space. This novel tool has promising uses in altered gravity environments as a sensitive non-invasive tool to determine alterations due to headward fluid shifts and elevated intracranial pressure. This article discusses the potential use of automated pupillometry in space for monitoring of astronaut health and neurological pathology.

Whole Exome Sequencing Reveals a Novel Homozygous Variant in the Ganglioside Biosynthetic Enzyme, ST3GAL5 Gene in a Saudi Family Causing Salt and Pepper Syndrome.

Salt and pepper developmental regression syndrome (SPDRS) is an autosomal recessive disorder characterized by epilepsy, profound intellectual disability, choreoathetosis, scoliosis, and dermal pigmentation along with dysmorphic facial features. GM3 synthase deficiency is due to any pathogenic mutation in the ST3 Beta-Galactoside Alpha-2,3-Sialyltransferase 5 (ST3GAL5) gene, which encodes the sialyltransferase enzyme that synthesizes ganglioside GM3. In this study, the Whole Exome Sequencing (WES) results presented a novel homozygous pathogenic variant, NM_003896.3:c.221T>A (p.Val74Glu), in the exon 3 of the ST3GAL5 gene. causing SPDRS with epilepsy, short stature, speech delay, and developmental delay in all three affected members of the same Saudi family. The results of the WES sequencing were further validated using Sanger sequencing analysis. For the first time, we are reporting SPDRS in a Saudi family showing phenotypic features similar to other reported cases. This study further adds to the literature and explains the role of the ST3GAL5 gene, which plays an important role, and any pathogenic variants that may cause the GM3 synthase deficiency that leads to the disease. This study would finally enable the creation of a database of the disease that provides a base for understanding the important and critical genomic regions that will help control intellectual disability and epilepsy in Saudi patients.

Cerebral fat embolism syndrome: diagnostic challenges and catastrophic outcomes: a case series.

Fat embolism syndrome is a rare but alarming, life-threatening clinical condition attributed to fat emboli entering the circulation. It usually occurs as a complication of long-bone fractures and joint reconstruction surgery. Neurological manifestations usually occur 12 to 72 hours after the initial insult. These neurological complications include cerebral infarction, spinal cord ischemia, hemorrhagic stroke, seizures, and coma. Other features include an acute confusional state, autonomic dysfunction, and retinal ischemia. In this case series, we describe three patients with fat embolism syndrome who presented with atypical symptoms and signs and with unusual neuroimaging findings. Cerebral fat embolism may occur without any respiratory or dermatological signs. In these cases, diagnosis is established after excluding other differential diagnoses. Neuroimaging using brain magnetic resonance imaging is of paramount importance in establishing a diagnosis. Aggressive hemodynamic and respiratory support from the beginning and consideration of orthopedic surgical intervention within the first 24 hours after trauma are critical to decreased morbidity and mortality.

Epilepsy and Hearing Loss in a Patient with a Rare Heterozygous Variant in the CACNA1H Gene.

The calcium voltage-gated channel subunit alpha 1 H (CACNA1H) is a gene present in eukaryotic cells located on chromosome 16 that encodes the T-type calcium channels, which are important for calcium influx and depolarization of cells. Pathogenic variants in CACNA1H cause autosomal dominant susceptibility to idiopathic generalized epilepsy 6 (OMIM: 611942), which is a broad term that encompasses several common seizure phenotypes. In this article, we reported a Saudi female with a heterozygous variant in the CACNA1H gene (OMIM: 607904) who had epilepsy and hearing loss. This is the first case to report the association of epilepsy and hearing loss with a variant in CACNA1H. We believe that variant may be the reason for developing both epilepsy and sensorineural hearing loss. Further studies are needed to identify the role of CACNA1H in the physiology of the ear to allow for a better understanding of the effects of mutations. In children who present with early childhood hearing loss, genetic studies in highly selected cases including those with a strong family history of hearing loss and epilepsy may help detect a CACNA1H variant early and help with the early screening and diagnosis of other associated disorders including subclinical epilepsy.

Clinical Outcomes of Radiological Treatment Modalities of Hepatocellular Carcinoma: A Single-Center Experience from Saudi Arabia.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Most patients with HCC are unsuitable for surgical therapies. Therefore, nonsurgical therapies play a central role in the management of this disease. Several percutaneous treatment modalities are available for HCC including radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and transarterial radioembolization (TARE). In this study, we aim to evaluate the clinical outcomes, morbidity and mortality rates, and survival rates of four treatment modalities for HCC (RFA, TACE, TARE, and Sorafenib) and compare the success rate of each modality. METHODS: A retrospective observational study was conducted at King Abdulaziz Medical City in Jeddah, Saudi Arabia. The inclusion criteria were composed of patients diagnosed with HCC who received RFA, TACE, TARE, or Sorafenib treatments between 2008 and 2017. The primary outcome of this study was recurrence-free patients at the last follow-up. RESULTS: A total of 108 patients were included in this study. The mean age of the patients was 68.01 ± 9.98 years. Eighty-Two patients (75.9%) underwent interventions with the intention to cure or stabilize HCC, while twentysix patients (24.1%) were started on Sorafenib as a palliative treatment. The five years recurrence-free rates were 41.2% with RFA, 40% with the combination of TACE and RFA, 23.3% with TACE, and 0% with TARE. All patients on Sorafenib died from advanced-stage HCC. CONCLUSION: This study provides further evidence for the efficacy of several treatment modalities for the management of HCC. RFA and the combination of TACE and RFA showed better outcomes with a recurrence-free rate reaching up to 40%. TACE had a moderate survival benefit up to 23.3%. TARE showed negative survival benefits. Sorafenib continues to be an important palliative treatment but does not offer curative potential.

Acute cervical dystonia following the BNT162b2 mRNA COVID-19 vaccine.

The coronavirus disease of 2019 (COVID-19) pandemic is caused by a novel coronavirus SARS-Cov-2. Four major vaccine types are being used to fight against this deadly pandemic and save precious human lives. All types of vaccines have been associated with a risk of neurological complications ranging from mild to severe. Cervical dystonia occurring after a COVID-19 vaccine was not previously reported in the literature. In this article, we describe a case of acute cervical dystonia occurring after the first dose of the BNT162b2 COVID-19 vaccine. We attribute the occurrence of cervical dystonia to the vaccine due to the temporal relationship. This report adds to the literature a possible rare side effect of a COVID-19 vaccine and contributes to the limited literature on potential neurological side effects of mRNA-based vaccines. The likely mechanism is autoimmune. Further research is needed to probe and study the exact mechanism.

Space neuroscience: current understanding and future research.

Space exploration is crucial for understanding our surroundings and establishing scientific concepts to explore, monitor, and save our planet's environment. However, the response of the human nervous system in the environment of space poses numerous challenges. Brain complexity explains the vulnerability and intrinsic difficulty of recalibration after disturbance. Over the millennia, the brain has evolved to function at 1-G. Studying the brain and its physiology in different environments may shed light on multiple conditions encountered on Earth that are yet to be solved and dictate collaboration at international levels. The nervous system is affected by several stressors due to microgravity, radiation, isolation, disruption of circadian rhythm, impaired sleep dynamics, and hypercapnia associated with space travel. In this article, we aim to review several aspects related to the nervous system in weightless conditions, as well as the development and future of the emerging field of "space neuroscience." Space neuroscience is a fascinating, embryonic field that requires significant development. The establishment of frameworks for the strategic development of space neuroscience is vital, as more research and collaboration are required to overcome these numerous and diverse challenges, minimize risks, and optimize crew performance during planetary operations.

Clinical and molecular characteristics of tectonic (TCTN1) gene-related Joubert syndrome in a Saudi boy.

Joubert syndrome (OMIM:609863) is a hereditary disorder characterized by hypotonia, developmental delay, and a distinctive cerebellar and brain stem malformation known as the molar tooth sign. Variants in tectonic genes TCTN1-3 have been described in a few patients with Joubert syndrome. Furthermore, Joubert syndrome attributed to variants in the TCTN1 (NM_001082538.2) gene has been only described in two reports. This report expands the clinical variability and molecular characterization of an emerging novel causative gene for Joubert syndrome in a Saudi boy born to non-consanguineous marriage with a c.1418del p.(Pro473Leufs*42) and c.800A > G p.(Tyr267Cys) representing a novel compound heterozygous variant of the TCTN1 gene identified by whole-exome sequencing and confirmed by Sanger sequencing. This is the first report of compound heterozygous Joubert syndrome type 13 from Saudi Arabia.

Rapid implementation of telemedicine in Neurology during the COVID-19 pandemic: Challenges in King Abdulaziz Medical City-Jeddah.

Telemedicine is defined as the remote medical practice of delivering healthcare services to the underserved using information and communication technology. It encompasses a wide range of medical activities, including diagnosis, treatment, disease prevention, and education. The coronavirus disease of 2019 (COVID-19) pandemic has caused significant social dislocation, negative economic impact, and a major change in medical practice in Saudi Arabia. Telemedicine has rapidly moved to the frontline of healthcare practice due to the demand for prevention and mitigation strategies. It has been encouraged and facilitated with huge government support. Herein, we describe the virtual clinical practice of the neurology department at King Abdulaziz Medical City-Jeddah in response to the COVID-19 pandemic. This narrative review is an urgent call to improve the perception and knowledge of both medical personnel and patients concerning telemedicine and to support the utilization of advanced information and communication technology.

The Use of Cannabis for Medical Purposes in the Arab World.

The legal landscape of cannabis (marijuana) has dramatically changed over the past few years in several countries worldwide. Many patients now have legal access to products derived from cannabis. In the Middle East, Lebanon became the first Arab country to legalize cannabis for medical and industrial use recently in 2020. Other Middle Eastern and Arab countries continue to completely ban the use of cannabis and products derived from cannabis. This article is a call to conduct medical research in the use of cannabis for medical purposes to determine the suitability and need for this substance in the Arab world. Based on these studies, evidence-based recommendations can be made to the highest authorities in the Arab countries for legalization or continued prohibition. As the international use of cannabis is increasing, the Arab countries may consider legalization of the substance to cover the unmet medical need and offer an additional treatment option for certain conditions.

The spectrum of muscle pathologies: Three decades of experience from a reference laboratory in Saudi Arabia.

BACKGROUND: When investigating patients with a suspected neuromuscular disorder, a muscle biopsy is considered an instrumental tool to reach a definitive diagnosis. There is a paucity of publications that assess the diagnostic utilization and yield of muscle biopsies. We intend to present our experience in this regard over an extended period of more than three decades. METHODS: This is an observational retrospective cohort study in which we collected pathology reports for muscle biopsies diagnosed at our reference lab between 1986 and 2017. RESULTS: We identified a total of 461 cases of muscle biopsy performed, which fulfilled the inclusion criteria. Pediatric cases defined as ≤14 years of age constituted a significant proportion of cases (n = 275, 60%). Normal biopsies were reported in 27% of cases (n = 124), and in 4%, the biopsies were non-diagnostic. The most common pathologies reported were non-specific myopathy (n = 72, 16%), dystrophy (n = 71, 15%), and neurogenic disorders (n = 60, 13%). CONCLUSION: In conclusion, the muscle biopsy will continue to play a crucial role, as a gold standard or as a complementary investigation, in the diagnosis of certain neuromuscular disorders. Increasing the yield and accuracy of muscle pathology should be the main concern and priority to neuropathologists reporting muscle biopsies. In addition, utilizing next-generation sequencing and other molecular techniques have changed the location of muscle biopsy in the algorithm of the diagnosis of neuromuscular disorders. This paper is an urgent call to establish the Saudi Neuropathology Society and the muscle pathology and neuromuscular disorders registry.

Hashimoto`s Encephalopathy Presenting with Progressive Cerebellar Ataxia.

Hashimoto`s encephalopathy is a rare neurological syndrome occurring in patients with autoimmune thyroid disease. The diagnosis of Hashimoto`s encephalopathy is based on the clinical picture with the presence of serum anti-thyroid antibodies regardless of the thyroid disorder. Acquired cerebellar ataxia associated with Hashimoto`s disease is a rare occurrence. In this article, we present a case who had progressive non-familial autoimmune pancerebellar disease in association with an increased level of thyroid peroxidase and thyroglobulin antibodies. The patient was managed aggressively with both intravenous immunoglobulins and plasma exchange, which stopped the progression of the disease and allowed for slow improvement. Early diagnosis of Hashimoto`s encephalopathy with autoimmune cerebellar ataxia and intervention with immunomodulatory therapy are of paramount importance. Close monitoring after steroid therapy is important since some patients with this rare disease might be resistant to steroid therapy and require aggressive immunomodulatory therapy.

Quality of life among multiple sclerosis patients in Saudi Arabia.

OBJECTIVE: To assess quality of life in multiple sclerosis (MS) patients and determine the factors associated with levels of quality of life in MS patients in a public hospital in Saudi Arabia. METHODS: A cross-sectional study was conducted from June 2016 to April 2017 in King Abdulaziz Medical City, Jeddah, Kingdom of Saudi Arabia. Multiple sclerosis patients attending the outpatient and inpatient services were approached and recruited to participate in the study. The Arabic version of EuroQOL-5 Dimensions instrument (EQ-5D) was utilized for the assessment of MS patients quality of life. RESULTS: Data on quality of life were obtained from 292 patients. The reported quality of life of MS patients as measured by the EQ-5D index value score was 0.31+/-0.51 and the EQ-VAS score was 73.87+/-23.41, respectively. It was found that quality of life determined numerically in the EQ-5D index value and EQ-VAS deteriorates proportionally according to the disease duration. CONCLUSION: Multiple sclerosis is associated with a considerable effect on the patients quality of life. It continues to be challenging to manage both medically and psychosocially. Clinicians should consider the assessment of quality of life as routine practice along with the other important measures including symptomatic evaluation, laboratory tests, and neuroimaging to provide a holistic care of their MS patients.