A recently published paper by Truong et al (link) providing two case reports of Smith-Magenis Syndrome (SMS) patients caught my eye yesterday:
SMS is caused by deletions of 17p11.2, a chromosomal region that encompasses the retinoic induced-1 (RAI1) gene, although some cases have been found to be caused by point mutations in RAI1 itself.
SMS is characterised by ‘intellectual disabilities, sleep disturbance, behavioural problems, and a variety of craniofacial, skeletal, and visceral anomalies’. At first glance this syndrome seems unrelated to BHD Syndrome since none of the classic triad of BHD feature in SMS, however, the authors report that one cases of SMS has suffered three incidences of spontaneous pneumothorax. This lead the authors to carry out mutational analysis of FLCN and subsequently identified the SNP c.871+36G>A. This mutation has previously been identified (Gunji et al., 2007; Cho et al., 2008; Wei et al., 2009) and has been classified a non-synonymous variant. However, alignment studies by the authors have shown that the mutation results in a missense mutation in the FLCN isoform 2.
My first impression is that this is an interesting finding, which may or may not prove to be significant since this has only been detected in a single case, but could this imply some kind of interaction of RAI1 and FLCN isoform 2 in the lungs?
Co-incidentally the article is currently free to downlaod and can be found in our BHD Article Library.