One novel and one recurrent mutation in IGHMBP2 gene, causing severe spinal muscular atrophy respiratory distress 1 with onset soon after birth.

A family with 2 siblings with severe spinal muscular atrophy with respiratory distress 1 (SMARD1) was genetically proved to be caused by mutations in IGHMBP2 gene. Both patients developed progressive muscular weakness and respiratory distress and died before 6 months of age. One novel deletion, c.780delG;p.(Gln260Hisfs*24), inherited from the father and a nonsense mutation, c.1488C>A;p.(Cys496*), inherited from the mother were detected. An attempt was made to correlate the genetic-clinical data available in the literature. The clinical case presented in this study might be considered as the most severe form of spinal muscular atrophy respiratory distress 1 reported so far, presumably because of the total absence of IGHMBP2 enzyme activity.