Mutations in NALP12 cause hereditary periodic fever syndromes.

NALP proteins, also known as NLRPs, belong to the CATERPILLER protein family involved, like Toll-like receptors, in the recognition of microbial molecules and the subsequent activation of inflammatory and immune responses. Current advances in the function of NALPs support the recently proposed model of a disease continuum bridging autoimmune and autoinflammatory disorders. Among these diseases, hereditary periodic fevers (HPFs) are Mendelian disorders associated with sequence variations in very few genes; these variations are mostly missense mutations whose deleterious effect, which is particularly difficult to assess, is often questionable. The growing number of identified sporadic cases of periodic fever syndrome, together with the lack of discriminatory clinical criteria, has greatly hampered the identification of new disease-causing genes, a step that is, however, essential for appropriate management of these disorders. Using a candidate gene approach, we identified nonambiguous mutations in NALP12 (i.e., nonsense and splice site) in two families with periodic fever syndromes. As shown by means of functional studies, these two NALP12 mutations have a deleterious effect on NF-kappaB signaling. Overall, these data identify a group of HPFs defined by molecular defects in NALP12, opening up new ways to manage these disorders. The identification of these first NALP12 mutations in patients with autoinflammatory disorder also clearly demonstrates the crucial role of NALP12 in inflammatory signaling pathways, thereby assigning a precise function to this particular member of an emerging family of proteins whose putative biological properties are currently inferred essentially through in vitro means.

[Congenital syphilis still exists]. / La syphilis congénitale n'a pas disparu.

INTRODUCTION: Even today screening for congenital syphilis must be performed and confirmed by appropriate serological tests and bacteriological samples. OBSERVATION: A newborn presented with an apparently materno-fetal or viral fetal disease. It was in fact congenital syphilis. The mother exhibited no risk factors for syphilis. Systematic serological search for syphilis was negative in the mother at 11 weeks of amenorrhea. No signs of primary or secondary syphilis had been observed during pregnancy. At twenty-nine weeks of amenorrhea, the mother presented a menace of preterm delivery and no tocolysis at 31 weeks. Examination of the newborn revealed clinical signs of aterno-fetal infection, without specificorientation. Initial bacteriological and virological analyses were negative. Screening for specific Treponema pallidum M-type immunoglobulines (IgM) on the 9th day of life, confirmed the diagnosis of congenital syphilis. COMMENTS: Diagnosis of congenital syphilis must not be eliminated during early serological screening: clinical suspicion must lead to further anamnesis again and serological tests both in the newborn and the mother.