A Common 3′UTR Variant of the PHOX2B Gene Is Associated With Infant Life-Threatening and Sudden Death Events in the Italian Population

• DOI: 10.3389/fneur.2021.642735
• Publication Date: 2021-03-19T05:54:07Z
• Authors: Tiziana Bachetti; Simona Bagnasco; Raffaele Piumelli; Antonella Palmieri; Isabella Ceccherini
• Keywords: Sudden Death

Heterozygous mutations in the Paired like homeobox 2b ( PHOX2B ) gene are causative of congenital central hypoventilation syndrome (CCHS), a rare monogenic disorder belonging to family neurocristopathies and due defective development autonomic nervous system. Most patients manifest sudden symptoms within 1 year birth, mainly represented by apnea cyanosis episodes. The appearance hypoxic manifestations CCHS their occurrence during sleep resemble two other unexplained perinatal disorders, apparent life-threatening event (ALTE) unexpected infant death (SUID), among which vast majority is (SIDS). Differently from CCHS, characterized Mendelian autosomal dominant inheritance, ALTE SIDS complex traits, where common genetic variants, together with external factors, may exert an additive effect likely manifesting only over “threshold.” Given similarities observed three abovementioned this work, we have analyzed frequency variants groups Italian idiopathic (IALTE) SUIDs/SIDS patients. Here, report that c * 161G>A (rs114290493) SNP 3′UTR (i) became overrepresented sets compared population matched healthy controls, (ii) associated decreased expression, mediated miR-204, microRNA already known bind gene. Overall, these results suggest that, at least population, does contribute, presumably association others or polymorphisms, confer susceptibility fatal disorders increasing miR-204 inducing expression down-regulation. However, preliminary observations need be confirmed on larger cohorts achieve clinical relevance.