Spectrum of Paediatric Lysosomal Storage Disorders in Oman

Objectives: The aim of this study was to look at the spectrum of paediatric lysosomal disorders in Oman. Lysosomal storage disorders (LSDs) are a heterogeneous group of inherited metabolic diseases. Few studies on the birth prevalence and prevalence of LSDs have been reported from the Arabian Peninsula. Methods: We studied 86 children with LSDs diagnosed over a period of nine years, from June 1998 to May 2007. Detailed clinical data, including age of onset, sex, age and mode of first presentation, and presence of consanguinity were collected. Results: Our data showed the combined birth prevalence for all LSDs in Oman to be around 1 in 4,700 live births. Sphingolipidoses was the most common group of disorder encountered (47.7%), followed by neuronal ceroid lipofuscinoses (NCL) (23.2%) and mucopolysaccharidoses (MPS) (23.2%). The proportion of consanguineous marriages in our series was found to be 87.5%. Conclusion: Our data represent the birth prevalence and clinicalspectrum of such disorders in Oman, one of the highly consanguineous societies in the Middle East.

Homozygous loss-of-function variants in FILIP1 cause autosomal recessive arthrogryposis multiplex congenita with microcephaly

Arthrogryposis multiplex congenita forms a broad group of clinically and etiologically heterogeneous disorders characterized by congenital joint contractures that involve at least two different parts of the body. Neurological and muscular disorders are commonly underlying arthrogryposis. Here, we report five affected individuals from three independent families sharing an overlapping phenotype with congenital contractures affecting shoulder, elbow, hand, hip, knee and foot as well as scoliosis, reduced palmar and plantar skin folds, microcephaly and facial dysmorphism. Using exome sequencing, we identified homozygous truncating variants in FILIP1 in all patients. FILIP1 is a regulator of filamin homeostasis required for the initiation of cortical cell migration in the developing neocortex and essential for the differentiation process of cross-striated muscle cells during myogenesis. In summary, our data indicate that bi-allelic truncating variants in FILIP1 are causative of a novel autosomal recessive disorder and expand the spectrum of genetic factors causative of arthrogryposis multiplex congenita

Mutations in PYCR2, Encoding Pyrroline-5-Carboxylate Reductase 2, Cause Microcephaly and Hypomyelination

Despite recent advances in understanding the genetic bases of microcephaly, a large number of cases of microcephaly remain unexplained, suggesting that many microcephaly syndromes and associated genes have yet to be identified. Here, we report mutations in PYCR2, which encodes an enzyme in the proline biosynthesis pathway, as the cause of a unique syndrome characterized by postnatal microcephaly, hypomyelination, and reduced cerebral white-matter volume. Linkage mapping and whole-exome sequencing identified homozygous mutations (c.355C>T [p.Arg119Cys] and c.751C>T [p.Arg251Cys]) in PYCR2 in the affected individuals of two consanguineous families. A lymphoblastoid cell line from one affected individual showed a strong reduction in the amount of PYCR2. When mutant cDNAs were transfected into HEK293FT cells, both variant proteins retained normal mitochondrial localization but had lower amounts than the wild-type protein, suggesting that the variant proteins were less stable. A PYCR2-deficient HEK293FT cell line generated by genome editing with the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 system showed that PYCR2 loss of function led to decreased mitochondrial membrane potential and increased susceptibility to apoptosis under oxidative stress. Morpholino-based knockdown of a zebrafish PYCR2 ortholog, pycr1b, recapitulated the human microcephaly phenotype, which was rescued by wild-type human PYCR2 mRNA, but not by mutant mRNAs, further supporting the pathogenicity of the identified variants. Hypomyelination and the absence of lax, wrinkly skin distinguishes this condition from that caused by previously reported mutations in the gene encoding PYCR2’s isozyme, PYCR1, suggesting a unique and indispensable role for PYCR2 in the human CNS during development

Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder

PURPOSE: Biallelic variants in TARS2, encoding the mitochondrial threonyl-tRNA-synthetase, have been reported in a small group of individuals displaying a neurodevelopmental phenotype, but with limited neuroradiological data and insufficient evidence for causality of the variants. METHODS: Exome or genome sequencing was carried out in 15 families. Clinical and neuroradiological evaluation was performed for all affected individuals, including review of 10 previously reported individuals. The pathogenicity of TARS2 variants was evaluated using in vitro assays, and a zebrafish model. RESULTS: We report 18 new individuals harboring biallelic TARS2 variants. Phenotypically, these individuals show developmental delay/intellectual disability, regression, cerebellar and cerebral atrophy, basal ganglia signal alterations, hypotonia, cerebellar signs and increased blood lactate. In vitro studies showed that variants within the TARS2301-381 region had decreased binding to Rag GTPases, likely impairing mTORC1 activity. The zebrafish model recapitulated key features of the human phenotype and unraveled dysregulation of downstream targets of mTORC1 signaling. Functional testing of the variants confirmed the pathogenicity in a zebrafish model. CONCLUSION: We define the clinico-radiological spectrum of TARS2-related mitochondrial disease, unveil the likely involvement of the mTORC1 signaling pathway as a distinct molecular mechanism, and establish a TARS2 zebrafish model as an important tool to study variant pathogenicity

Zooplankton of Oman Coastal Waters

Monthly sampling during daytime was carried out in 2007-2011 at Bandar Al-Khyran (23.51oN, 58.72oE) which is the largest semi-enclosed bay on the southern end of the Sea of Oman with about 4 km2 in surface area and an average depth of 10 m. Zooplankton were represented by Copepoda (79%), Cladocera (9%), Oikopleuriddae (7%), Chaetognatha (3%), and Decapoda (~2%) comprising the major part of the total zooplankton abundance. Among copepods, 27 species constituted ~75% of total copepod abundance. Changes of copepod abundance have not had a pronounced seasonal pattern. Instead, a multiple peak structure in monthly fluctuations was observed, on the level of genera as well as the abundance of species. Amplitudes and timing of the copepod peak abundance were markedly different during the studied years

Zooplankton of Oman Coastal Waters

Monthly sampling during daytime was carried out in 2007-2011 at Bandar Al-Khyran (23.51oN, 58.72oE) which is the largest semi-enclosed bay on the southern end of the Sea of Oman with about 4 km2 in surface area and an average depth of 10 m. Zooplankton were represented by Copepoda (79%), Cladocera (9%), Oikopleuriddae (7%), Chaetognatha (3%), and Decapoda (~2%) comprising the major part of the total zooplankton abundance. Among copepods, 27 species constituted ~75% of total copepod abundance. Changes of copepod abundance have not had a pronounced seasonal pattern. Instead, a multiple peak structure in monthly fluctuations was observed, on the level of genera as well as the abundance of species. Amplitudes and timing of the copepod peak abundance were markedly different during the studied years

Differential Expression of Oman’s Wild Lavender, Lavandula subnuda for Chemical Composition towards Medicinal and Aromatic Application

Plants have been used directly or indirectly as medicines for over 5000 years as a source of antibiotics, antineoplastics, analgesics, and cardio-protective, among others. Approximately 70–90% of the population in developing countries continue to use ancient medicines based on plant extracts for treatment. Recently, the isolation and identification of biologically active compounds and molecules from nature have led to the discovery of new therapeutics, prompting the improvement of the health and pharmaceutical sectors. Phytochemicals revolve around the pharmaceutical industry's research and development (R&D) sector as a source of new molecules leading to the development of new novel drugs. Given the above, the present investigation addresses the differential nature of wild lavender (Lavandula subnuda Benth) plants of diverse locations in Oman with respect to their chemical composition of the essential oil in addition to morphological characters and chlorophyll contents of leaves to explore the possibility of isolating its prime chemical compounds on a commercial scale in perfumery industry. There are no previous studies so far who have reported on essential oil recovery and chemical composition exclusively in respect of Lavandula subnuda. Composite samples of ten randomly selected plants were collected from wadi habitats of four diversified locations. Edaphic features of managed sites were recorded, and their soil chemical contents were determined following instructions using S1 Titan/Tracer 5/CTX equipment of Bruker developed based on energy dispersive X-ray fluorescence (EDXRF). Morphological traits were measured using a ruler, and chlorophyll contents were recorded using the atLEAF CHL Plus chlorophyll meter as atLEAF values. The essential oil was extracted using ETHO X's advanced microwave extraction system and analyzed for chemical compounds using GC-MS analysis on Shimadzu GC-2010 Plus gas chromatograph. The experimental data were analyzed statistically, wherever required, by applying basic statistics of the EXCEL -16 version. The results indicated that in general, the Lavandula subnuda plants of locations of high altitudes had higher expressivity in all the morphological traits and chlorophyll contents than those of low altitudes. The essential oil recovery, however, was found to be higher from the plant samples of lower altitudes (0.70 to 0.79% (w/w)) than from those of higher mountains/ altitudes (0.15 to 0.18% (w/w)). The pattern of values of commonly occurring chemical contents of essential oils was different. Each essential oil's top ten chemical compounds contributed about 80% of the total in four locations. Of the ten top chemical compounds, eight compounds, namely D-Germacrene (42.67%) from Wadi Al-Khod, Estragole (32%) and Linalool (23.89%) from Wadi Halban), trans-Borneol (23.46%) and 4-Terpineol (18.73%) from Wadi Najd Al-Waqba and Kessane (18.60%), beta-cis-Caryophyllene (13.68%) and beta-Elemene (10.618%) from Wadi Al-Hayul, were found highest in quantity and had huge potential for further application. It is concluded that there exists a higher possibility of adapting Good Agriculture Practice (GAP) to produce the highest herbage yield of vegetative parts of Lavandula subnuda plants based on morphological features under wild conditions to extract these compounds on a commercial scale in both the pharmaceutical and perfumery industries.Keywords: Morphology, Chlorophyll, Chemical compounds, Differential Expression, Lavandula subnuda,, Lamiacea

Differential Expression of Oman’s Wild Lavender, Lavandula subnuda for Chemical Composition towards Medicinal and Aromatic Application

Plants have been used directly or indirectly as medicines for over 5000 years as a source of antibiotics, antineoplastics, analgesics, and cardio-protective, among others. Approximately 70–90% of the population in developing countries continue to use ancient medicines based on plant extracts for treatment. Recently, the isolation and identification of biologically active compounds and molecules from nature have led to the discovery of new therapeutics, prompting the improvement of the health and pharmaceutical sectors. Phytochemicals revolve around the pharmaceutical industry's research and development (R&D) sector as a source of new molecules leading to the development of new novel drugs. Given the above, the present investigation addresses the differential nature of wild lavender (Lavandula subnuda Benth) plants of diverse locations in Oman with respect to their chemical composition of the essential oil in addition to morphological characters and chlorophyll contents of leaves to explore the possibility of isolating its prime chemical compounds on a commercial scale in perfumery industry. There are no previous studies so far who have reported on essential oil recovery and chemical composition exclusively in respect of Lavandula subnuda. Composite samples of ten randomly selected plants were collected from wadi habitats of four diversified locations. Edaphic features of managed sites were recorded, and their soil chemical contents were determined following instructions using S1 Titan/Tracer 5/CTX equipment of Bruker developed based on energy dispersive X-ray fluorescence (EDXRF). Morphological traits were measured using a ruler, and chlorophyll contents were recorded using the atLEAF CHL Plus chlorophyll meter as atLEAF values. The essential oil was extracted using ETHO X's advanced microwave extraction system and analyzed for chemical compounds using GC-MS analysis on Shimadzu GC-2010 Plus gas chromatograph. The experimental data were analyzed statistically, wherever required, by applying basic statistics of the EXCEL -16 version. The results indicated that in general, the Lavandula subnuda plants of locations of high altitudes had higher expressivity in all the morphological traits and chlorophyll contents than those of low altitudes. The essential oil recovery, however, was found to be higher from the plant samples of lower altitudes (0.70 to 0.79% (w/w)) than from those of higher mountains/ altitudes (0.15 to 0.18% (w/w)). The pattern of values of commonly occurring chemical contents of essential oils was different. Each essential oil's top ten chemical compounds contributed about 80% of the total in four locations. Of the ten top chemical compounds, eight compounds, namely D-Germacrene (42.67%) from Wadi Al-Khod, Estragole (32%) and Linalool (23.89%) from Wadi Halban), trans-Borneol (23.46%) and 4-Terpineol (18.73%) from Wadi Najd Al-Waqba and Kessane (18.60%), beta-cis-Caryophyllene (13.68%) and beta-Elemene (10.618%) from Wadi Al-Hayul, were found highest in quantity and had huge potential for further application. It is concluded that there exists a higher possibility of adapting Good Agriculture Practice (GAP) to produce the highest herbage yield of vegetative parts of Lavandula subnuda plants based on morphological features under wild conditions to extract these compounds on a commercial scale in both the pharmaceutical and perfumery industries.Keywords: Morphology, Chlorophyll, Chemical compounds, Differential Expression, Lavandula subnuda,, Lamiacea