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1.  A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population 
BMC Medical Genetics  2012;13:72.
Background
Zellweger syndrome (ZS) is a peroxisome biogenesis disorder due to mutations in any one of 13 PEX genes. Increased incidence of ZS has been suspected in French-Canadians of the Saguenay-Lac-St-Jean region (SLSJ) of Quebec, but this remains unsolved.
Methods
We identified 5 ZS patients from SLSJ diagnosed by peroxisome dysfunction between 1990–2010 and sequenced all coding exons of known PEX genes in one patient using Next Generation Sequencing (NGS) for diagnostic confirmation.
Results
A homozygous mutation (c.802_815del, p.[Val207_Gln294del, Val76_Gln294del]) in PEX6 was identified and then shown in 4 other patients. Parental heterozygosity was confirmed in all. Incidence of ZS was estimated to 1 in 12,191 live births, with a carrier frequency of 1 in 55. In addition, we present data suggesting that this mutation abolishes a SF2/ASF splice enhancer binding site, resulting in the use of two alternative cryptic donor splice sites and predicted to encode an internally deleted in-frame protein.
Conclusion
We report increased incidence of ZS in French-Canadians of SLSJ caused by a PEX6 founder mutation. To our knowledge, this is the highest reported incidence of ZS worldwide. These findings have implications for carrier screening and support the utility of NGS for molecular confirmation of peroxisomal disorders.
doi:10.1186/1471-2350-13-72
PMCID: PMC3483250  PMID: 22894767
Zellweger syndrome; Founder effect; Peroxisome biogenesis disorders; Next generation sequencing
2.  Nephrectomy in patients with Caroli’s and ADPKD may be associated with increased morbidity 
Autosomal dominant polycystic kidney disease (ADPKD), characterized by multiple bilateral renal cysts, is the most common inherited disorder of the kidney and an important cause of end-stage renal disease (ESRD). Caroli’s disease is a much less frequent condition with ectasia of the intrahepatic biliary system. A clear association between autosomal recessive and Caroli’s disease has been described, but only 4 cases of ADPKD and Caroli’s disease have been reported with 2 postoperative mortalities. The aim of this case is to increase the awareness of intra-operative and postoperative complications. A 66 year-old male was diagnosed with ADPKD and Caroli’s disease with hepatosplenomegaly and 4 episodes of ascending cholangitis. After 3 years of hemodialysis for ESRD, he received a cadaveric renal allograft. Subsequently, he developed paroxysmal atrial fibrillation. Upon anticoagulation, he developed multiple episodes of gross hematuria from the left native kidney. After the anticoagulation therapy was discontinued, he underwent bilateral nephrectomies of his native kidneys. Intra-operatively, a splenic laceration could not be managed conservatively. Therefore, splenectomy was performed. In addition, he developed ascending cholangitis post-operatively that was treated with antibiotics. He was discharged on postoperative day 18. Genetic testing revealed that the patient is heterozygote for a large deletion in PKD1 gene, which encompasses all tested exons (exons 1–44).
doi:10.5489/cuaj.10054
PMCID: PMC3104419  PMID: 21470545

Results 1-2 (2)