Segmental auxiliary liver transplantation in dogs: a search for an ideal graft--illusion or reality?

Segmental auxiliary liver transplantation (SALT) has been carried out in 13 mongrel dogs to assess the possibility of a certain size of liver segment to accept without sequelae the total splanchnic and arterial blood normally diverted to the liver of the host. Prednisone (1 mg/daily) and azathioprine (2 mg/kg daily) were used as immunosuppression. Five dogs died during the first hours after the operation. Three because of technical failure and two of acute portal hypertension secondary to total portal and arterial blood diversion in dogs with liver segments of 195 +/- 49 g as a result of overloading of the graft. The remaining 8 dogs were divided into: 4 dogs into which a liver segment (195 +/- 49 g) was transplanted (group A) and 4 dogs in which a liver segment (385 +/- 85 g) was used (group B). Partial portal and total arterial blood diversion in group A dogs was not associated with portal hypertension but resulted in poor function of the graft and in poor survival. In contrast, the graft in group B dogs was able to cope with both total or partial portal blood and with a normal arterial blood diversion. Infection and graft rejection prohibited long-term survival (8-28 days). Data from this study support the view that the present technique of SALT with a graft corresponding to 300-400 g in mongrel dogs of about 30 kg is a potential alternative as temporary liver support in the diseased anima

Pathogenic variants in three families with distal muscle involvement

Three families suspected of distal hereditary motor neuropathy underwent genetic screening with the aim to identify the molecular defect underlying the disease. The description of the identification reflects the shift in molecular diagnostics that was made during the last decades. Our candidate gene approach yielded a known pathogenic variant in BSCL2 (p.Asn88Ser) in one family, and via a CMT-capture, in HSPB1 (p.Arg127Trp), in addition to five other variations in Charcot-Marie-Tooth-related genes in the proband of the second family. In the third family, using whole exome sequencing, followed by linkage-by-location, a three base pair deletion in exon 33 of MYH7 (p.Glu1508del) was found, a reported pathogenic allele albeit for a myopathy. After identification of the causative molecular defect, cardiac examination was performed for patients of the third family and this demonstrated abnormalities in three out of five affected family members. Heterogeneity and expansion of clinical phenotypes beyond known characteristics requires a wider set of genes to be screened. Whole exome/genome analysis with limited prior clinical information may therefore be used to precede a detailed clinical evaluation in cases of large families, preventing screening of a too narrow set of genes, and enabling the identification of novel disease-associated genes. In our cases, the variants had been reported, and co-segregation analysis confirmed the molecular diagnosis

Evidence for locus heterogeneity in the Bethlem myopathy and linkage to 2q37

The Bethlem myopathy, a childhood onset autosomal dominant myopathy with joint contractures, has recently been localized to 21q in a series of Dutch families and the α1 and α2 subunits of type VI collagen (COL6A1 and COL6A2) have been postulated as candidate genes. We investigate a large family of French Canadian descent (family 1489) in which the Bethlem myopathy is segregating. Family 1489 is unlinked to the region of interest on 21q, thus demonstrating locus heterogeneity within the Bethlem myopathy classification. In view of the localization of the genes coding the α1 and α2 subunits of type VI collagen on chromosome 21q, we carried out linkage analysis on chromosome 2q where the α3 subunit of type VI collagen has been localized. We demonstrate linkage to markers in this region, define the region of disease gene localization, and confirm by FISH analysis that COL6A3 is located within the interval of interest making COL6A3 a feasible candidate gene for the Bethlem myopathy