The first new study, entitled, “SMA-causing missense mutations in survival motor neuron (Smn) display a wide range of phenotypes when modeled in Drosophila” published in the August issue of Plos Genetics, reports on the conservative features of missense mutations in both humans and a model system with Drosophila melanogaster.
Spinal Muscular Atrophy (SMA) is the leading cause of child death among genetic disorders, and is caused by loss of function mutations in the survival motor neuron 1 (Smn1) gene. The disease is characterized by spinal muscular atrophy due to death of motor neurons triggered by the absence of/defective SMN protein.
In this report, the authors studied twelve Smn missense mutations, identified in human SMA patients, but here they used Drosophila melanogaster as a model system to study their functional role. The authors found SMA patient-derived mutations lead to different ages of symptomatic onset and life expectancies in Drosophila. Moreover, they found a high level of conservation between the biochemical and structure-function in Drosophila and human SMN.
When crossed back with wild-type, Drosophila displays intermediate phenotypes, thus Smn missense mutations display incomplete dominance. However, when wild-type SMN is overexpressed, it can suppress the activity of the mutant protein. On the contrary, the authors found that certain SMN mutant proteins can deactivate the wild-type protein.
The authors thus highlight the use of model systems to study complex human diseases and, in the case of SMA, they showed the role of potential dominant negative interactions between wild-type and mutant SMN subunits.
New Perspectives Into Childhood Spinal Muscular Atrophy Diagnosis
The second study, entitled, “A mixed methods exploration of families’ experiences of the diagnosis of childhood spinal muscular atrophy” published in the European Journal of Human Genetics reports a comprehensive study of families with SMA children experiences.
In Australia, where the study was completed, the carrier frequency for SMA is 1 in every 41 children. The SMA diagnosis is subsequently classified in three different types according to age of onset symptoms and severity. There is a lack, however, of family history data that ultimately leads to the disease’s diagnosis, a key factor for diagnostic outcomes.
In this study, a team of researchers at the Murdoch Children’s Research Institute, Department of Paediatrics, at the University of Melbourne, Australia collected data from interviews and national survey of families with SMA to build a comprehensive report on their experiences. In general, the authors found that the period until a definitive diagnosis lasted for a long time, according to the families’ experiences. Thus, this period was emotionally challenging and frustrating. Upon the first sign of symptoms, all the families reported consulting multiple health professionals and examinations before the final diagnosis. However, the confirmation of SMA was a devastating event for the families. All of them reported that the diagnosis, in their view, could have been delivered more efficiently and much earlier. Some still reported that this could have benefited the diagnosis impact and the family’s emotional state. Ultimately, the families supported a population carrier screening preferable to newborn screening.
In conclusion, despite the increasing recognition of SMA in children, the prolonged period until a confirmed diagnosis is still reported as the major negative impact on these families.
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