Intellectual disability (ID) affects 1%–3% of the general population. We recently reported on a family with autosomal-recessive mental retardation with anterior maxillary protrusion and strabismus ...(MRAMS) syndrome. One of the reported patients with ID did not have dysmorphic features but did have temporal lobe epilepsy and psychosis. We report on the identification of a truncating mutation in the
SOBP that is responsible for causing both syndromic and nonsyndromic ID in the same family. The protein encoded by the
SOBP, sine oculis binding protein ortholog, is a nuclear zinc finger protein. In mice, Sobp (also known as Jxc1) is critical for patterning of the organ of Corti; one of our patients has a subclinical cochlear hearing loss but no gross cochlear abnormalities. In situ RNA expression studies in postnatal mouse brain showed strong expression in the limbic system at the time interval of active synaptogenesis. The limbic system regulates learning, memory, and affective behavior, but limbic circuitry expression of other genes mutated in ID is unusual. By comparing the protein content of the
+/jc to
jc/jc mice brains with the use of proteomics, we detected 24 proteins with greater than 1.5-fold differences in expression, including two interacting proteins, dynamin and pacsin1. This study shows mutated
SOBP involvement in syndromic and nonsyndromic ID with psychosis in humans.
: Congenital circumferential skin folds can be found in individuals with no additional defects, as well as in patients with multiple congenital anomalies and developmental abnormalities. Current ...data point to etiological heterogeneity of syndromic cases. We describe a 7‐month‐old girl with a novel combination of symmetrical congenital circumferential skin folds, dysmorphic features, and multiple congenital abnormalities. Examination of the patient revealed symmetrical congenital circumferential skin folds and dysmorphic features, as well as multiple congenital anomalies including nasal pyriform aperture stenosis, ventricular septal defect, absent spleen, camptodactyly, and severe psychomotor retardation. Skin biopsy demonstrated subcutaneous fat extending into the superficial and deep reticular dermis. Sequencing of the CDON, SHH, ZIC2, SIX3, and TGIF genes (associated with holoprosencephaly) did not disclose pathogenic alterations. Extensive review of previously described cases of syndromic congenital circumferential skin folds did not reveal a similar combination of clinical and histopathological findings.
This study reports on a hitherto undescribed autosomal recessive syndrome characterised by dysmorphic features and multiple congenital anomalies together with severe neurological impairment, chorea ...and seizures leading to early death, and the identification of a gene involved in the pathogenesis of the disease.
Homozygosity mapping was performed using Affymetrix Human Mapping 250k NspI arrays. Sequencing of all coding exons of the candidate genes was performed with primer sets designed using the Primer3 program. Fluorescence activated cell sorting was performed using conjugated antibody to CD59. Staining, acquisition and analysis were performed on a FACSCalibur flow cytometer.
Using homozygosity mapping, the study mapped the disease locus to 18q21.32-18q22.1 and identified the disease-causing mutation, c.2126G→A (p.Arg709Gln), in PIGN, which encodes glycosylphosphatidylinositol (GPI) ethanolamine phosphate transferase 1, a protein involved in GPI-anchor biosynthesis. Arginine at the position 709 is a highly evolutionarily conserved residue located in the PigN domain. The expression of GPI linked protein CD59 on fibroblasts from patients as compared to that in a control individual showed a 10-fold reduction in expression, confirming the pathogenic consequences of the mutation on GPI dependent protein expression.
The abundant expression of PIGN in various tissues is compatible with the diverse phenotypic features observed in the patients and with the involvement of multiple body systems. The presence of developmental delay, hypotonia, and epilepsy combined with multiple congenital anomalies, especially anorectal anomalies, should lead a clinician to suspect a GPI deficiency related disorder.
The molecular basis for primary hereditary hypertriglyceridemia has been identified in fewer than 5% of cases. Investigation of monogenic dyslipidemias has the potential to expose key metabolic ...pathways. We describe a hitherto unreported disease in ten individuals manifesting as moderate to severe transient childhood hypertriglyceridemia and fatty liver followed by hepatic fibrosis and the identification of the mutated gene responsible for this condition. We performed SNP array-based homozygosity mapping and found a single large continuous segment of homozygosity on chromosomal region 12q13.12. The candidate region contained 35 genes that are listed in Online Mendelian Inheritance in Man (OMIM) and 27 other genes. We performed candidate gene sequencing and screened both clinically affected individuals (children and adults with hypertriglyceridemia) and also a healthy cohort for mutations in GPD1, which encodes glycerol-3-phosphate dehydrogenase 1. Mutation analysis revealed a homozygous splicing mutation, c.361−1G>C, which resulted in an aberrantly spliced mRNA in the ten affected individuals. This mutation is predicted to result in a truncated protein lacking essential conserved residues, including a functional site responsible for initial substrate recognition. Functional consequences of the mutation were evaluated by measuring intracellular concentrations of cholesterol and triglyceride as well as triglyceride secretion in HepG2 (hepatocellular carcinoma) human cells lines overexpressing normal and mutant GPD1 cDNA. Overexpression of mutant GPD1 in HepG2 cells, in comparison to overexpression of wild-type GPD1, resulted in increased secretion of triglycerides (p = 0.01). This finding supports the pathogenicity of the identified mutation.
Energi terbarukan seperti PLTS (Pembangkit Listrik Tenaga Surya) memiliki peran yang penting dalam mendukung pertahanan negara. Keberlanjutan, kemandirian energi, fleksibilitas dalam distribusi dan ...penggunaan, serta komitmen terhadap inovasi dan teknologi ramah lingkungan adalah faktor-faktor utama yang menjadikan PLTS sebagai solusi energi strategis dalam sektor pertahanan. Dengan mengadopsi dan mengintegrasikan PLTS ke dalam sistem pertahanan, negara dapat memastikan operasional militer yang lebih efisien, keamanan energi yang lebih besar, dan posisi yang lebih kuat di panggung internasional.Integrasi PLTS dalam sistem energi di fasilitas militer memiliki potensi yang besar dalam mengurangi ketergantungan pada sumber energi fosil, meningkatkan ketersediaan energi, dan memperkuat komitmen dalam menjaga lingkungan hidup. Dengan demikian, PLTS dapat menjadi alternatif yang potensial untuk memenuhi kebutuhan energi di fasilitas militer dan meningkatkan efektivitas operasi militer. Metodologi penelitian yang akan menggunakan pendekatan kuantitatif dan kualitatif melalui beberapa metode pengumpulan data: Studi dokumentasi, Survey lapangan dan Analisi GIS. Pemanfaatan Pembangkit Listrik Tenaga Surya (PLTS) dengan 53,60% penyinaran matahari dan luas area 400.000 m² dapat memberikan dampak positif terhadap operasi dan strategi pertahanan negara dalam hal efisiensi energi, keberlanjutan, dan kemandirian. Jumlah panel yang dapat diinstal : Luas area yang dapat digunakan = 400.000 m² x 70% = 280.000 m² . Jumlah panel = 280.000 m² / 1,6 m² per panel = 175.000 panel. Dengan asumsi setiap panel memiliki kapasitas 250 Watt. Total kapasitas PLTS akan menjadi: Kapasitas total = 175.000 panel x 250 Watt = 43.750.000 Watt = 43,75 MW. Adapun kapasitas yang di butuhkan adalah sebesar 606 Volt tegangan listrik dengan daya 200 kVA dan Arus 330 Ampere.
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