RESUMEN
Many neurodevelopmental defects are linked to perturbations in genes involved in housekeeping functions, such as those encoding ribosome biogenesis factors. However, how reductions in ribosome biogenesis can result in tissue and developmental specific defects remains a mystery. Here we describe new allelic variants in the ribosome biogenesis factor AIRIM primarily associated with neurodevelopmental disorders. Using human cerebral organoids in combination with proteomic analysis, single-cell transcriptome analysis across multiple developmental stages, and single organoid translatome analysis, we identify a previously unappreciated mechanism linking changes in ribosome levels and the timing of cell fate specification during early brain development. We find ribosome levels decrease during neuroepithelial differentiation, making differentiating cells particularly vulnerable to perturbations in ribosome biogenesis during this time. Reduced ribosome availability more profoundly impacts the translation of specific transcripts, disrupting both survival and cell fate commitment of transitioning neuroepithelia. Enhancing mTOR activity by both genetic and pharmacologic approaches ameliorates the growth and developmental defects associated with intellectual disability linked variants, identifying potential treatment options for specific brain ribosomopathies. This work reveals the cellular and molecular origins of protein synthesis defect-related disorders of human brain development. Highlights: AIRIM variants reduce ribosome levels specifically in neural progenitor cells. Inappropriately low ribosome levels cause a transient delay in radial glia fate commitment.Reduced ribosome levels impair translation of a selected subset of mRNAs.Genetic and pharmacologic activation of mTORC1 suppresses AIRIM-linked phenotypes.
RESUMEN
Cavernous hemangiomas (CHs) are vascular structures comprising abnormally dilated blood vessel clusters. This anomaly is estimated to occur in approximately one out of every 500-600 people. Individuals often show the first sign of cavernous hemangiomas in their second or third decade. Therefore, the presentation of this disorder is not common in children. This study presents a five year-old-girl who developed abruptly nearly fixed right-sided eye deviation and incoordination after a short course of viral infection. In physical examination, she had left peripheral facial, right eye oculomotor, and left abducens nerve palsy. Her brain's computed tomography (CT) scan revealed hemorrhages in the posterior aspect of the pons and some areas of the hemispheres in different stages. Following brain magnetic resonance imaging (MRI), multiple popcorn ball low-signal T2* lesions with both supra- and infratentorial locations with marked peripheral hypo intensities were seen. These findings were in favor of multiple cavernous hemangiomas of the brain. The novelty of this case was due to observing cavernous angiomas in both supra- and infratentorial spaces in pediatric age.
RESUMEN
Imerslund-Gräsbeck syndrome is a rare condition caused by vitamin B12 deficiency and proteinuria. In this article, we reported the case of a 10-year-old girl with imbalance and urinary incontinence. The case had cerebellar ataxia as the primary manifestation. The disequilibrium had progressed gradually within three weeks and was consistent with the symptoms of cerebellar involvement and urinary incontinence. Brain and cervico-thoraco-lumbar magnetic resonance imaging were normal. The patient had elevated lactate dehydrogenase (LDH=4775), in addition to macrocytic anemia, on laboratory examinations; thus, the possibility of malignancy was raised. Then, bone marrow aspiration was performed, showing hypercellular marrow with megaloblastic changes. This finding proved megaloblastic anemia. Regarding the low prevalence of vitamin B12 deficiency in healthy individuals, extensive studies were performed to find out the cause. The serum level of vitamin B12 was found to be lower than the normal range. Although urinalysis revealed significant proteinuria, further nephrological investigations did not indicate any abnormalities. No evidence of serious problems was observed in the gastrointestinal tract study, and metabolic studies were normal. Finally, based on the obtained data, Imerslund-Gräsbeck syndrome was recognized. Patient was treated by vitamin B12 injection, leading to improved balance, and in one-month follow-up, she was able to walk independently, and the cerebellar symptoms had greatly disappeared; however, proteinuria persisted.
RESUMEN
This report describes a 3-month-old boy with isolated left ventricular noncompaction admitted to a medical facility due to heart failure and dysrhythmia. His electrocardiogram showed a short PR interval and a normal QRS complex after abortion of supraventricular tachycardia in favor of Lown-Ganong-Levine syndrome or enhanced atrioventricular nodal conduction.
