Expanding the Phenotypic Spectrum of Alazami Syndrome: Two Unrelated Spanish Families.

Alazami syndrome is a rare disorder with an autosomal recessive inheritance caused by pathogenic biallelic variants in the LARP7 gene. Clinically, it is mainly characterized by short stature, intellectual disability, and dysmorphic facial features. However, the phenotype is not yet well-defined because less than 50 cases have been described to date. Here, we report three new patients from two unrelated Spanish families who, in addition to the defined features of Alazami syndrome, also exhibit unique features that broaden the phenotypic spectrum of the syndrome. Moreover, we describe the novel frameshift variant c.690_699delins27 in the LARP7 gene, in which loss of function is a known mechanism of Alazami syndrome.

Ictericia en el lactante: más allá de la atresia de vías biliares / Jaundice in infants: beyond biliary atresia

La colestasis es una entidad que se define por la elevación de bilirrubina conjugada sérica (más de 2 mg/dl o más del 20% del total) y que suele acompañarse de clínica de ictericia, coluria y acolia/hipocolia. Existen múltiples entidades causantes de tal cuadro, pero en el caso de la colestasis neonatal, es fundamental descartar con urgencia la atresia de vías biliares extrahepáticas (AVBE), ya que precisa una intervención quirúrgica de derivación de flujo biliar de forma temprana por sus implicaciones pronósticas futuras. Ante una colestasis neonatal en la que se ha descartado la AVBE, el diagnóstico diferencial se realizará en función de la evaluación de distintos factores, tales como la cifra de gamma-glutamil transferasa (GGT), el valor de los ácidos biliares, si hay o no sospecha de enfermedad metabólica o por la presencia de otras anomalías asociadas. (AU)

Cholestasis is a condition defined by elevated direct bilirubin serum levels (>2 mg/dl or >20% of total bilirubin) and is usually accompanied by jaundice, dark urine, and acholia. Many diseases that cause this condition, but in the case of neonatal cholestasis, it is essential to rule out extrahepatic bile duct atresia (EBVA) on an urgent basis, since it requires early surgical intervention to divert bile flow due to its impact on future outcomes. In the presence of neonatal cholestasis in which EBVA has been ruled out, the differential diagnosis is based on the evaluation of different factors, such as gamma-glutamyl transferase (GGT) and bile acid levels, the suspicion of metabolic disease or the presence of other associated abnormalities. (AU)

Modulation of copper deficiency responses by diurnal and circadian rhythms in Arabidopsis thaliana.

Copper homeostasis under deficiency is regulated by the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE7 (SPL7) transcription factor. The daily oscillating expression of two SPL7-dependent copper deficiency markers, COPPER TRANSPORTER (COPT2) and IRON SUPEROXIDE DISMUTASE (FSD1), has been followed by quantitative PCR and in promoter:LUCIFERASE transgenic plants. Both genes showed circadian and diurnal regulation. Under copper deficiency, their expression decreased drastically in continuous darkness. Accordingly, total copper content was slightly reduced in etiolated seedlings under copper deficiency. The expression of SPL7 and its targets COPT2 and FSD1 was differently regulated in various light signalling mutants. On the other hand, increased copper levels reduced the amplitude of nuclear circadian clock components, such as GIGANTEA (GI). The alteration of copper homeostasis in the COPT1 overexpression line and spl7 mutants also modified the amplitude of a classical clock output, namely the circadian oscillation of cotyledon movements. In the spl7 mutant, the period of the oscillation remained constant. These results suggest a feedback of copper transport on the circadian clock and the integration of rhythmic copper homeostasis into the central oscillator of plants.

Comparison of global responses to mild deficiency and excess copper levels in Arabidopsis seedlings.

Copper is an essential micronutrient in higher plants, but it is toxic in excess. The fine adjustments required to fit copper nutritional demands for optimal growth are illustrated by the diverse, severe symptoms resulting from copper deficiency and excess. Here, a differential transcriptomic analysis was done between Arabidopsis thaliana plants suffering from mild copper deficiency and those with a slight copper excess. The effects on the genes encoding cuproproteins or copper homeostasis factors were included in a CuAt database, which was organised to collect additional information and connections to other databases. The categories overrepresented under copper deficiency and copper excess conditions are discussed. Different members of the categories overrepresented under copper deficiency conditions were both dependent and independent of the general copper deficiency transcriptional regulator SPL7. The putative regulatory elements in the promoter of the copper deficiency overrepresented genes, particularly of the iron superoxide dismutase gene FSD1, were also analysed. A 65 base pair promoter fragment, with at least three GTAC sequences, was found to be not only characteristic of them all, but was responsible for most of the FSD1 copper-dependent regulations. Moreover, a new molecular marker for the slight excess copper nutritional status is proposed. Taken together, these data further contribute to characterise copper nutritional responses in higher plants.