COVID-19 versus SARS: A comparative review.

The two genetically similar severe acute respiratory syndrome coronaviruses, SARS-CoV-1 and SARS-CoV-2, have each been responsible for global epidemics of vastly different scales. Although both viruses arose from similar origins, they quickly diverged due to differences in their transmission dynamics and spectrum of clinical presentations. The potential involvement of multiple organs systems, including the respiratory, cardiac, gastrointestinal and neurological, during infection necessitates a comprehensive understanding of the clinical pathogenesis of each virus. The management of COVID-19, initially modelled after SARS and other respiratory illnesses, has continued to evolve as we accumulate more knowledge and experience during the pandemic, as well as develop new therapeutics and vaccines. The impact of these two coronaviruses has been profound for our health care and public health systems, and we hope that the lessons learned will not only bring the current pandemic under control, but also prevent and reduce the impact of future pandemics.

Clinical and genomic characteristics of LAMA2 related congenital muscular dystrophy in a patients' cohort from Qatar. A population specific founder variant.

Congenital LAMA2 related muscular dystrophy (LAMA2-RD), the most commonly recognized type of congenital muscular dystrophies, has been described in patients' cohorts from Europe and the UK but not from Middle-Eastern. This study aimed to reveal the prevalence, clinical and genomic characteristics of congenital LAMA2-RD in a patient's cohort of 17 families (21 patients) from the Gulf and Middle East. Affected subjects exhibited the classic phenotype of generalized hypotonia, developmental delay, and progressive muscular weakness. Despite the homogeneous background of most of our patients, clinical variability was evident; however, none of our patients was able to achieve independent ambulation. The associated features of nephrocalcinosis, infantile-onset osteopenia, and cardiac arrest were first described in this study. LAMA2 mutations constituted 48% of the genetic causes underlying congenital muscular dystrophies (CMDs) in our patients. We estimated a point prevalence of 0.8 in 100.000 for LAMA2-RD in Qatar, relatively higher compared to that described in Europe's studies. The founder mutation and high rate of consanguinity are potential contributors. This study identified five LAMA2 truncating variants, two novel and three recurrent, of which the c.6488delA-frameshift that was found in 12 unrelated Qatari families, highlighting a founder mutation in Qatari patients. The two novel variants involved an acceptor splice site and N-terminus deletion that removes the LAMA2 promoter, exon1, and part of intron1. The "residual" expression of LAMA2 transcript and protein associated with this large N-terminus deletion suggested an alternative promoter that, while seems to be activated, acts less efficiently.

Identification of a novel CNTNAP1 mutation causing arthrogryposis multiplex congenita with cerebral and cerebellar atrophy.

Arthrogryposis multiplex congenital, the occurrence of multiple joint contractures at birth, can in some cases be accompanied by insufficient myelination of peripheral nerves, muscular hypotonia, reduced tendon reflexes, and respiratory insufficiency. Recently mutations in the CASPR/CNTN1 complex have been associated with similar severe phenotypes and CNTNAP1 gene mutations, causing loss of the CASPR protein, were shown to cause severe, prenatal onset arthrogryposis multiplex congenita in four unrelated families. Here we report a consanguineous Arab family from Qatar with three children having an early lethal form of arthrogryposis multiplex congenita and a novel frameshift mutation in CNTNAP1. We further expand the existing CNTNAP1-associated phenotype to include profound cerebral and cerebellar atrophy.

NT5C2 novel splicing variant expands the phenotypic spectrum of Spastic Paraplegia (SPG45): case report of a new member of thin corpus callosum SPG-Subgroup.

BACKGROUND: Hereditary Spastic Paraplegia (HSP) is a genetically heterogeneous group of neurodegenerative diseases. Thin Corpus Callosum (TCC) associated HSP is a distinguished subgroup of complex forms. Purines and pyrimidine, the basic DNA and RNA components, are regulating the cell metabolism, having roles in signal transduction, energy preservation and cellular repair. Genetic defects in nucleotide metabolism related genes have been only recently implicated in brain and neurodegenerative diseases' pathogenesis. CASE PRESENTATION: We present a consanguineous Qatari family with two brothers, 9 and 3 years, who displayed a characteristic phenotype of early onset and markedly-severe spasticity with tiptoe walking, delayed dysarthric speech, persistent truncal hypotonia, and multiple variable-sized areas of brownish skin discoloration appearing at different places on the body. A clinical diagnosis suggestive of complex hereditary spastic paraplegia (HSP) was set after the family had the second affected child. Whole genome sequencing identified a novel homozygous NT5C2 splice site mutation (NM_012229.4/NM_001134373.2: c.1159 + 1G > T) that recessively segregated in family members. Brain MRI revealed dysgenic and thin corpus callosum (TCC) with peri-trigonal white matter cystic changes in both affected boys, whereas a well-developed corpus callosum with normal white matter was shown in their apparently normal brother, who found to be a carrier for the mutant variant. This mutation led to skipping of exon 14 with removal of 58 amino acid residues at the C-terminal half. The aberrantly spliced NT5C2 showed substantial reduction in expression level in the in-vitro study, indicating marked instability of the mutant NT5C2 protein. CONCLUSION: The present report expands the phenotypic spectrum of SPG45 and confirms NT5C2-SPG45 as a member of the rare TCC SPG-subtypes. Homozygous alteration in NT5C2 seems essential to produce central white matter developmental defects. The study highlights the importance of cytosolic II 5'-nucleotidase (NT5C2) in maintaining the normal balance of purines' pool in the brain, which seems to play a pivotal role in the normal development of central white matter structures.

Evaluation of SNP calling using single and multiple-sample calling algorithms by validation against array base genotyping and Mendelian inheritance.

BACKGROUND: With diminishing costs of next generation sequencing (NGS), whole genome analysis becomes a standard tool for identifying genetic causes of inherited diseases. Commercial NGS service providers in general not only provide raw genomic reads, but further deliver SNP calls to their clients. However, the question for the user arises whether to use the SNP data as is, or process the raw sequencing data further through more sophisticated SNP calling pipelines with more advanced algorithms. RESULTS: Here we report a detailed comparison of SNPs called using the popular GATK multiple-sample calling protocol to SNPs delivered as part of a 40x whole genome sequencing project by Illumina Inc of 171 human genomes of Arab descent (108 unrelated Qatari genomes, 19 trios, and 2 families with rare diseases) and compare them to variants provided by the Illumina CASAVA pipeline. GATK multi-sample calling identifies more variants than the CASAVA pipeline. The additional variants from GATK are robust for Mendelian consistencies but weak in terms of statistical parameters such as TsTv ratio. However, these additional variants do not make a difference in detecting the causative variants in the studied phenotype. CONCLUSION: Both pipelines, GATK multi-sample calling and Illumina CASAVA single sample calling, have highly similar performance in SNP calling at the level of putatively causative variants.

Oculo-ectodermal syndrome: A case report and further delineation of the syndrome.

Oculo-ectodermal syndrome (OES - OMIM 600628), also known as Toriello Lacassie Droste syndrome, is a very rare condition, first described by Toriello et al., in 1993. OES has been proposed to be a mild variant of encephalocraniocutaneous lipomatosis (ECCL). It is characterized by aplasia cutis congenita (ACC), epibulbar dermoids, coarctation of the aorta, arachnoid cysts in the brain, seizure disorder, hyperpigmented nevi, non-ossifying fibromas and a predisposition to develop giant cell tumors of the jaw. There are few reported cases of OES worldwide but with no definite diagnostic criteria yet. We present a case in a child with unilateral hyperpigmented nevi and ACC on the scalp, ocular lesions (lipodermoid cysts and coloboma), temporal arachnoid cyst, spinal lipomatosis and aortic coarctation with the aim of enhancing the foundation to establish diagnostic criteria for this condition. It additionally serves as a teaching point to emphasize the importance of pursuing a definite diagnosis when faced with such a multisystem illness, to counsel patients and their parents regarding long term morbidity and overall prognosis.

New subtype of familial intracranial calcification in a mother and two children.

We report on a mother and two children from a consanguineous Arab Qatari family demonstrating a highly distinctive pattern of intracranial calcification involving the globus pallidus, posterior limb of the internal capsule, genu of the corpus callosum, and deep white matter. Both siblings, a girl and boy, presented with neonatal seizures without subsequent deterioration in neurological function. The girl demonstrated mild to moderate psychomotor delay but her brother and mother showed completely normal development. All three affected individuals were normocephalic. To the best of our knowledge this phenotype represents a novel disorder of inherited brain calcification, which may be recognizable on computerized tomography brain imaging in other cases. Although the disease shows apparent autosomal dominant inheritance, the high degree of consanguinity in the family leaves open the possibility of pseudo-dominance for an autosomal recessive trait.

Are heterocygotes for classical homocystinuria at risk of vitamin B12 and folic acid deficiency?

OBJECTIVES/DESIGN: Comparative cross-sectional study to assess homocysteine and vitamin status in carriers of CBS gene mutations. METHOD: Subjects included 34 parents (13 males, 21 females, age 27-59 years) of 30 patients with classical homocystinuria due to homozygous cystathionine beta-synthase deficiency. Control subjects were matched for gender and age (13 males, 21 females, age 25-59 years). All subjects were of Qatari origin, had normal liver and renal function tests and had not taken drugs or vitamin supplements prior to the study. The concentrations of homocysteine, folic acid and vitamins B6 and B12 in blood were determined after an overnight fast. RESULTS: Heterozygous carriers had significantly increased fasting levels of homocysteine compared to controls (9.1 vs. 8.1 micromol/l, P=0.012). Both folic acid (328 vs. 478 pmol/l, P=0.002) and vitamin B12 concentrations (232 vs. 287 pmol/l, P=0.013) were reduced whilst there was no significant difference in vitamin B6 levels between the two groups (5.8 vs. 6.44 microg/l). CONCLUSIONS: Increased homocysteine concentrations in CBS gene mutation carriers are associated with reduced concentrations of folic acid and vitamin B12 in blood. In view of the adverse effects of mild hyperhomocysteinemia, routine testing of vitamin status in parents of homocystinuria patients may be warranted. The causal relationship and pathophysiological consequences are uncertain; it is likely that CBS gene mutation carriers need higher doses of dietary vitamins.

Acute bacterial meningitis in Qatar.

OBJECTIVE: To study the changes in the epidemiology, clinical and bacteriological profiles of bacterial meningitis in the era of the Haemophilus influenzae type b (Hib)vaccine and pneumococcus resistance. METHODS: This is a retrospective study of children aged <12 years admitted to the Hamad Medical Corporation, Qatar between January 1998 through December 2002 with positive cerebrospinal fluid culture. RESULTS: We described 64 patients with culture proven bacterial meningitis. In infants <3 months (n=29 [45%]), the most common organism was Group B Streptococcus (GBS) (20%). Children >3 months (n=35 [55%]); Hib (25%) and Streptococcus pneumoniae (STP) (20%) were the most common organisms before introduction of Hib vaccination. A significant drop of Hib infections were noticed after introduction of the vaccine. Fever, neck stiffness, seizure, vomiting, and bulging fontanel were the most frequent presenting features. Group B Streptococcus were sensitive to ampicillin and cefotaxime with no resistance detected. Forty percent of STP isolates were resistant to penicillin and 12% were resistant to ceftriaxone. Fifty percent of Hib were resistant to ampicillin; while none of Hib were resistant to ceftriaxone. No case of Listeria monocytogenes meningitis was diagnosed. Morbidity was 28%, and one patient expired (2%) after Klebsiella pneumoniae meningitis. Streptococcus pneumoniae was associated with the highest morbidity (62%) while Hib had zero morbidity in our patients. CONCLUSION: Bacterial meningitis is a serious illness with a significant morbidity and mortality. Haemophilus influenzae type b infection decreased which indicated an effective vaccination. As there is 12% bacterial resistance of STP reported against ceftriaxone; We recommend Cefotaxime for infants <3 months while ceftriaxone plus vancomycin as empiric therapy for older patients with community acquired bacterial meningitis. A pneumococcal vaccination may further decrease the incidence of meningitis in our community. A continuos surveillance to detect changes in the microbiology of organisms causing bacterial meningitis or their sensitivity in our community is essential to update these recommendations.

Pattern of headache in school children in the State of Qatar.

OBJECTIVES: The aim of this study is to determine the prevalence rate and impact of headache in school children on school attendance with particular attention to migraine. METHODS: A cross sectional survey was conducted among the school children ranging from 6-17 years old over a period from March 2001 to April 2003. The study was carried out in 10 primary, preparatory and secondary schools. Subjects were selected by multistage stratified sampling procedure. This involved 851 children studying in the first to tenth year of school in the State of Qatar. RESULTS: The present study showed that the prevalence rate of recurrent headache was 85% and migraine 11.9%. Comparing gender frequency of headache, it was noted that it was higher in female students (86.5%) than males (81%). In respect of age, it was observed that the oldest children had more frequent episodes of headache, the highest rate was in the age group of 11-15 years old (49%). The most common triggers were fatigue (35.8%) and lack of sleep (17.6%). The most common symptoms that occurred before headache were change in mood for female students (39.1%) and blurred vision for males (34.6%). The impact of headache on children was frequent absence from school (80%), which affected their school performance. CONCLUSION: The current study indicated the high prevalence of headache among school children in Qatar, and its effect on school attendance and performance.

Sandhoff disease (GM2 Gangliosidoses) in a premature patient with bronchopulmonary dysplasia.

We report a female premature infant with bronchopulmonary dysplasia and Sandhoff disease. The clue for diagnosis was the fundoscopy examination. We discuss this rare disease with unusual presentation of intrauterine growth retardation, premature delivery, and bronchopulmonary dysplasia.

Clinical presentation of acute bacterial meningitis in Qatar.

OBJECTIVE: To study the changes in the epidemiology of bacterial meningitis in the era of the Hemophilus influenzae (H. influenzae) type b vaccine and pneumoccous resistance. METHODS: Retrospective study which included patients admitted to Hamad Medical Corporation, Doha, Qatar between January 1998 through to December 2000 with positive cerebrospinal fluid culture. RESULTS: Thirty-seven patients with culture proven bacterial meningitis were described. Streptococcus pneumoniae (S. pneumoniae) and H. influenzae were the most common organisms, accounting for 30% and 24% of cases. Fever, neck stiffness, vomiting, and bulging fontanel were the most frequent presenting features. Fifty four percent of S. pneumoniae isolates were resistant to penicillin, and 22% of H. influenzae were resistant to ampicillin, but both were sensitive to ceftriaxone. No cases of Listeria monocytogenes meningitis were diagnosed. Morbidity was 32%, and mortality 5%. Poor outcome was associated with altered mental status on admission. CONCLUSION: Bacterial meningitis is a serious illness in our community with significant morbidity and mortality. Streptococcus pneumoniae and H. influenzae are the most frequent pathogens causing meningitis in our community. As there is no bacterial resistance (S. pneumoniae and H. influenzae) reported against ceftrixone, we recommend ceftriaxone alone as empiric therapy for patients with no comorbid conditions presenting with community acquired bacterial meningitis. A continuous surveillance for changes in the microbiology of organisms causing bacterial meningitis or their sensitivity in our community is essential to update these recommendations.

Sandhoff disease (GM2 gangliosidoses) in a premature patient with bronchopulmonary dysplasia.

We report a female premature infant with bronchopulmonary dysplasia and Sandhoff disease. The clue for diagnosis was the fundoscopy examination. We discuss this rare disease with unusual presentation of intrauterine growth retardation, premature delivery, and bronchopulmonary dysplasia.