Early onset of Chanarin-Dorfman syndrome with severe liver involvement in a patient with a complex rearrangement of ABHD5 promoter

BACKGROUND: \u3b1/\u3b2-hydrolase domain-containing protein 5 (ABHD5) plays an important role in the triacylglycerols (TAG) hydrolysis. Indeed, ABHD5 is the co-activator of adipose triglyceride lipase (ATGL), that catalyses the initial step of TAG hydrolysis. Mutations in ABHD5 gene are associated with the onset of Chanarin-Dorfman syndrome (CDS), a rare autosomal recessive lipid storage disorder, characterized by non-bullous congenital ichthyosiform erythroderma (NCIE), hepatomegaly and liver steatosis. CASE PRESENTATION: We describe here a 5-years-old Brazilian child who presented with NCIE at birth and diffuse micro and macro-vesicular steatosis on liver biopsy since she was 2 years old. Molecular analysis of coding sequence and putative 5' regulatory region of ABHD5 gene was performed. A homozygous novel deletion, affecting the promoter region and the exon 1, was identified, confirming the suspected diagnosis of CDS for this patient. RT-PCR analysis showed that the genomic rearrangement completely abolished the ABHD5 gene expression in the patient, while only a partial loss of expression was detected in her parents. This is the first report describing the identification of a large deletion encompassing the promoter region of ABHD5 gene. The total loss of ABHD5 expression may explain the early onset of CDS and the severe liver involvement. After molecular diagnosis, the patient started a special diet, poor in fatty acids with medium chain triglycerides (MCT), and showed hepatic and dermatologic improvement in spite of severe molecular defect. CONCLUSIONS: This case report extends the spectrum of disease-causing ABHD5 mutations in CDS providing evidence for a novel pathogenic mechanism for this rare disorder. Moreover, our preliminary data show that early diagnosis and prompt treatment of neutral lipid accumulation might be useful for CD patients

Mirror production for the Cherenkov telescopes of the ASTRI Mini-Array and of the MST project for the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) is the next ground-based $\gamma$-ray observatory in the TeV $\gamma$-ray spectral region operating with the Imaging Atmospheric Cherenkov Technique. It is based on almost 70 telescopes of different class diameters - LST, MST and SST of 23, 12, and 4 m, respectively - to be installed in two sites in the two hemispheres (at La Palma, Canary Islands, and near Paranal, Chile). Several thousands of reflecting mirror tiles larger than 1 m$^2$ will be produced for realizing the segmented primary mirrors of a so large number of telescopes. Almost in parallel, the ASTRI Mini-Array (MA) is being implemented in Tenerife (Canary Islands), composed of nine 4 m diameter dual-mirror Cherenkov telescopes (very similar to the SSTs). We completed the mirror production for all nine telescopes of the ASTRI MA and two MST telescopes (400 segments in total) using the cold glass slumping replication technology. The results related to the quality achieved with a so large-scale production are presented, also discussing the adopted testing methods and approaches. They will be very useful for the adoption and optimization of the quality assurance process for the huge production (almost 3000 m$^2$ of reflecting surface) of the MST and SST CTA telescopes

The BDNFval66met polymorphism and individual differences in temperament in 4-month-old infants: A pilot study

Individual differences in infants’ temperament are under genetic control. We investigated the association between brain-derived-neurotrophic-factor (BDNFval66met) polymorphism and temperament in 63 full-term infants. Met-carriers (N = 25) had lower Regulatory capacities compared to val-homozygotes (N = 38). These findings suggest that the BDNF polymorphism affects early temperament individual differences

Clinical and genetic characterization of a Chanarin Dorfman Syndrome patient born to diseased parents

Background: Chanarin Dorfman Syndrome (CDS) is a rare autosomal recessive disorder characterized by ichthyosiform non-bullous erythroderma and variable involvement of the liver and the neuromuscular system. In CDS patients, the accumulation of neutral lipids inside cytoplasmic lipid droplets has been demonstrated in different tissues. To date, ninety families with this disease have been described worldwide; most of them are from Mediterranean countries. Case presentation: In this report, we describe a consanguineous Turkish family with typical features of CDS. The parents are first cousins and are both diseased. At the age of eight, their child presented CDS with non-bullous congenital ichthyosiform erythroderma, hepatosteatosis, hepatomegaly and ectropion. Electromyographic examination is compatible with myopathy. A five-year-old cousin of the child is also affected by CDS. She was born to non-affected consanguineous parents. Mutation analysis of the ABHD5 gene revealed the previously reported mutation, N209X, which is the most frequent in Turkish patients. Lipid vacuoles, also known as Jordan's anomaly, are detectable in their leucocytes. Conclusions: To the best of our knowledge, this is the first report of a CDS family in which both parents and their child are affected by CDS. To date, the child does not present a more severe clinical phenotype compared with those of his relatives or other CDS patients of the same age. These findings suggest that high levels of triacylglycerol accumulation, that may be supposed to be present in high amount inside the ooplasm, did not affect embryo development and foetal growth