A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders

Innes AM, Boycott KM, Puffenberger EG, Redl D, MacDonald IM, Chudley AE, Beaulieu C, Perrier R, Gillan T, Wade A, Parboosingh JS. A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders. Bardet‐Biedl syndrome (BBS) is a multisystem genetically heterogeneous disorder, the clinical features of which are largely the consequence of ciliary dysfunction. BBS is typically inherited in an autosomal recessive fashion, and mutations in at least 14 genes have been identified. Here, we report the identification of a founder mutation in the BBS2 gene as the cause for the increased incidence of this developmental disorder in the Hutterite population. To ascertain the Hutterite BBS locus, we performed a genome‐wide single nucleotide polymorphism (SNP) analysis on a single patient and his three unaffected siblings from a Hutterite family. The analysis identified two large SNP blocks that were homozygous in the patient but not in his unaffected siblings, one of these regions contained the BBS2 gene. Sequence analysis and subsequent RNA studies identified and confirmed a novel splice site mutation, c.472‐2A>G, in BBS2. This mutation was also found in homozygous form in three subsequently studied Hutterite BBS patients from two different leuts, confirming that this is a founder mutation in the Hutterite population. Further studies are required to determine the frequency of this mutation and its role, if any, in the expression of other ciliopathies in this population.     

Adaptive coping strategies in patients with chronic pain conditions and their interpretation of disease

Background  

We examined which adaptive coping strategies, referring to the concept of 'locus of disease control', were of relevance for patients with chronic pain conditions, and how they were interconnected with patients' life satisfaction and interpretation of disease.     

Functional study of lipids of PNH red cell membranes: susceptibility of liposomes to reactive lysis

Lipids extracted with chloroform-methanol from red blood cell membranes of 7 PNH and 13 control subjects were used for the preparation of liposomes, which were then examined with the reactive lysis test. PNH liposomes lysed to a higher extent than control liposomes as indicated by the higher dilution of the limiting complement reagent that was necessary to lyse 50% of the PNH liposomes. A similar finding was also observed with liposomes made of lipids from AET-treated red cells. The enhanced reactive lysis can be attributed to the polar lipid fraction, as indicated by the increased lysis of hybrid liposomes prepared from this polar lipids extracted from PNH erythrocyte membrane and lipids extracted from normal erythrocyte membrane. The increased susceptibility to reactive lysis does not seem to be specific of PNH liposomes, since it was also observed with liposomes prepared from lipids of red cells from beta-thalassemia major and autoimmune hemolytic disease.     

Esophageal strictures in children: treatment by serial balloon catheter dilatation

Grüntzig balloon catheters were used to dilate ten esophageal strictures in eight infants and children. Five infants who had anastomotic strictures following esophageal atresia repair gained complete resolution of their strictures, usually after one or two dilatations. Three older children who had strictures following esophageal re-operation or reconstruction required longer courses of dilatations to achieve consistent esophageal patency. The technique failed in two chronic strictures of two and one-half and nine years' duration. Balloon catheter dilatation, begun in the early postoperative period, is a safe, effective method for dilating esophageal strictures.