Bases moléculaires du gigantisme hypophysaire

peer reviewe

Three years pilot of spinal muscular atrophy newborn screening turned into official program in Southern Belgium

Motor neuron disease; Population screeningMalaltia de la neurona motora; Cribratge de poblacióEnfermedad de la neurona motora; Cribado de poblaciónThree new therapies for spinal muscular atrophy (SMA) have been approved by the United States Food and Drug Administration and the European Medicines Agency since 2016. Although these new therapies improve the quality of life of patients who are symptomatic at first treatment, administration before the onset of symptoms is significantly more effective. As a consequence, newborn screening programs have been initiated in several countries. In 2018, we launched a 3-year pilot program to screen newborns for SMA in the Belgian region of Liège. This program was rapidly expanding to all of Southern Belgium, a region of approximately 55,000 births annually. During the pilot program, 136,339 neonates were tested for deletion of exon 7 of SMN1, the most common cause of SMA. Nine SMA cases with homozygous deletion were identified through this screen. Another patient was identified after presenting with symptoms and was shown to be heterozygous for the SMN1 exon 7 deletion and a point mutation on the opposite allele. These ten patients were treated. The pilot program has now successfully transitioned into the official neonatal screening program in Southern Belgium. The lessons learned during implementation of this pilot program are reported.This pilot study is supported by AveXis, Biogen, Roche, the ABMM (Association Belge contre les Maladies neuro-Musculaires), Minister's Office Alda GREOLI (Wallonia-Brussels Community) and donations from individuals

Dutch Founder SDHB Exon 3 Deletion in Patients with Pheochromocytoma-Paraganglioma in South Africa.

OBJECTIVE: Screening studies have established genetic risk profiles for diseases such as multiple endocrine neoplasia type 1 (MEN1) and pheochromocytoma-paraganglioma (PPGL). Founder effects play an important role in regional/national epidemiology of endocrine cancers, particularly PPGL. Founder effects in the Netherlands have been described for various diseases, some of which established themselves in South Africa due to Dutch emigration. The role of Dutch founder effects in South Africa have not been explored in PPGL. DESIGN: We performed a single-center study in South Africa of the germline genetic causes of isolated/syndromic neuroendocrine tumors. METHODS: Next-generation panel and multiplex ligand-dependent probe amplification for endocrine neoplasia risk genes. RESULTS: From a group of 13 patients we identified six with PPGL, four with sporadic or familial isolated pituitary adenomas (FIPA), and three with clinical MEN1; genetic variants were identified in 9/13 cases. We identified the Dutch founder exon 3 deletion in SDHB in two apparently-unrelated individuals with distinct ethnic backgrounds that had metastatic PPGL. Asymptomatic carriers with this Dutch founder SDHB exon 3 deletion were also identified. Other PPGL patients had variants in SDHB, SDHD and three MEN1 variants were identified among MEN1 and young-onset pituitary adenoma patients. CONCLUSIONS: This is the first identification of a Dutch founder effect for PPGL in South Africa. Awareness of the presence of this exon 3 SDHB deletion could promote targeted screening at a local level. Insights into PPGL genetics in South Africa could be achieved by studying existing patient databases for Dutch founder mutations in SDHx genes

Three years pilot of spinal muscular atrophy newborn screening turned into official program in Southern Belgium.

Three new therapies for spinal muscular atrophy (SMA) have been approved by the United States Food and Drug Administration and the European Medicines Agency since 2016. Although these new therapies improve the quality of life of patients who are symptomatic at first treatment, administration before the onset of symptoms is significantly more effective. As a consequence, newborn screening programs have been initiated in several countries. In 2018, we launched a 3-year pilot program to screen newborns for SMA in the Belgian region of Liège. This program was rapidly expanding to all of Southern Belgium, a region of approximately 55,000 births annually. During the pilot program, 136,339 neonates were tested for deletion of exon 7 of SMN1, the most common cause of SMA. Nine SMA cases with homozygous deletion were identified through this screen. Another patient was identified after presenting with symptoms and was shown to be heterozygous for the SMN1 exon 7 deletion and a point mutation on the opposite allele. These ten patients were treated. The pilot program has now successfully transitioned into the official neonatal screening program in Southern Belgium. The lessons learned during implementation of this pilot program are reported

High-resolution measurements of an upwelling filament during the CAIBEX survey

Upwelling filaments have been studied for several years. We aim to explain the general process in terms of potential vorticity: An injection of positive vorticity north of the Cape forces the jet to turn offshore, in virtue of the principle of vorticity conservation. The Regional Ocean Modeling System (ROMS) is implemented in the Cape Ghir region, with horizontal resolution lower than 1 km. A set of process-oriented experiments has been designed in order to determine the mechanisms at the origin of the filament.CAIBE