Alstrom syndrome is a rare autosomal recessive multi-organ syndrome caused by variations in ALMS1 gene. We explore the underlying genetic cause in one case of Alstrom syndrome who manifasted childhood obesity, hyperinsulinemia, and acanthosis using the whole-exome sequencing, to improve clinicians′ awareness of the disease. The proband presented with obesity, acanthosis, hyperinsulinemia, and fatty liver in childhood, but without typical manifestations of Alstrom syndrome, such as retinal degeneration, hearing impairment and cardiomyopathty. Whole-exome sequencing revealed that the proband carried a complex heterozygous ALMS1 mutation, including c. 1A>T(p.M1? ) and c. 8971G>C, p. D2991H. Family verification found that his father wass heterozygous for the c. 1A>T mutation, his mother was heterozygous for the c. 8971G>C mutation, and the sister′s ALMS1 gene detection and clinical phenotype were normal, which was consistent with the autosomal recessive inheritance pattern. Through bioinformatics analysis, the new mutations c. 1A>T and c. 8971G>C in the ALMS1 gene were identified as deleterious mutations. In this study, a single case of Alstrom syndrome was reported with childhood obesity, acanthosis nigricans, and hyperinsulinemia as the main manifestations, and two new ALMSl gene mutations were discovered, which expanded the phenotype and pathogenic mutation spectrum of Alstrom syndrome.

OBJECTIVE: To evaluate the recovery of patients with end-stage renal disease (ESRD) receiving kidney transplant from cardiac death donors, and to assess graft survival in China from this type of donor. METHODS: A total of 48 cases of patients with ESRD have received the kidneys from cardiac death donors in our hospital between February 2010 and March 2012. We retrospectively analyzed data on the preoperative and postoperative serum creatinine concentrations, on the survival of recipients and allografts with a view to investigating prognoses after this type of kidney transplant. RESULTS: Primary non-function (PNF) did not occur in any of the 48 recipients. Delayed graft function (DGF) occurred in 18 of 48 (37.5%) of kidneys from cardiac death donors, but the occurrence of DGF did not adversely influence patient's survival (P=0.098) or graft survival (P=0.447). Seven of 48 (14.6%) recipients lost their graft. Over a median follow-up period of 8 months (range 0.5-23 months), 39 of 41(95.1%) recipients' graft function had fully recovered. The actuarial graft and patient's survival rates at 1, 3, 6 and 12 months after transplantation were 95.7%, 93.0%, 90.0%, 87.5%, and 100%, 94.9%, 90%, 87.5%, respectively. CONCLUSION As the legislation of donation after brain death (DBD) has not been ratified in China, the use of kidneys from cardiac death donors might be an effective way to increase the number of kidneys available for transplantation here. Our experience indicates good short- and mid-term outcomes with transplants from cardiac death donors.
Adult ; Brain Death ; Cadaver ; Death, Sudden, Cardiac ; Delayed Graft Function ; epidemiology ; Female ; Graft Survival ; Humans ; Kidney Transplantation ; Male ; Middle Aged ; Tissue Donors ; statistics & numerical data

OBJECTIVE: To investigate the effect of calmodulin (CaM) and its mutants on binding to voltage-gated Na channel isoleucine-glutamine domain (Na1.2 IQ). METHODS: The cDNA of Na1.2 IQ was constructed by PCR technique, CaM mutants CaM, CaM and CaM were constructed with Quickchange site-directed mutagenesis kit (QIAGEN). The binding of Na1.2 IQ to CaM and CaM mutants under calcium and calcium free conditions were detected by pull-down assay. RESULTS: Na1.2 IQ and CaM were bound to each other at different calcium concentrations, while GST alone did not bind to CaM. The binding affinity of CaM and Na1.2 IQ at [Ca]-free was greater than that at 100 nmol/L [Ca] ( < 0.05). In the absence of calcium, the binding amount of CaM wild-type to Na1.2 IQ was greater than that of its mutant, and the binding affinity of CaM to Na1.2 IQ was the weakest among the three mutants ( < 0.05). CONCLUSIONS The binding ability of CaM and CaM mutants to Na1.2 IQ is Ca-dependent. This study has revealed a new mechanism of Na1.2 regulated by CaM, which would be useful for the study of ion channel related diseases.
Calcium ; metabolism ; Calmodulin ; genetics ; metabolism ; Mutation ; NAV1.2 Voltage-Gated Sodium Channel ; metabolism ; Protein Binding ; genetics