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1.  Diagnosis of Bardet-Biedl Syndrome in Consecutive Pregnancies Affected with Echogenic Kidneys and Polydactyly in a Consanguineous Couple 
Case Reports in Genetics  2013;2013:159143.
Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathic human genetic disorder with variable expression that is difficult to diagnose in pregnancy without known risk factors. Homozygosity testing has been shown to be a useful tool in identifying BBS mutations and candidate genes in affected individuals. We present the first case of prenatal diagnosis of BBS in consecutive pregnancies aided by homozygosity testing via SNP microarray analysis. This case demonstrates a novel approach to the evaluation of recurrent echogenic kidneys in consanguineous couple with no significant family history.
doi:10.1155/2013/159143
PMCID: PMC3603615  PMID: 23533844
2.  Correlation of rare coding variants in the gene encoding human glucokinase regulatory protein with phenotypic, cellular, and kinetic outcomes 
Defining the genetic contribution of rare variants to common diseases is a major basic and clinical science challenge that could offer new insights into disease etiology and provide potential for directed gene- and pathway-based prevention and treatment. Common and rare nonsynonymous variants in the GCKR gene are associated with alterations in metabolic traits, most notably serum triglyceride levels. GCKR encodes glucokinase regulatory protein (GKRP), a predominantly nuclear protein that inhibits hepatic glucokinase (GCK) and plays a critical role in glucose homeostasis. The mode of action of rare GCKR variants remains unexplored. We identified 19 nonsynonymous GCKR variants among 800 individuals from the ClinSeq medical sequencing project. Excluding the previously described common missense variant p.Pro446Leu, all variants were rare in the cohort. Accordingly, we functionally characterized all variants to evaluate their potential phenotypic effects. Defects were observed for the majority of the rare variants after assessment of cellular localization, ability to interact with GCK, and kinetic activity of the encoded proteins. Comparing the individuals with functional rare variants to those without such variants showed associations with lipid phenotypes. Our findings suggest that, while nonsynonymous GCKR variants, excluding p.Pro446Leu, are rare in individuals of mixed European descent, the majority do affect protein function. In sum, this study utilizes computational, cell biological, and biochemical methods to present a model for interpreting the clinical significance of rare genetic variants in common disease.
doi:10.1172/JCI46425
PMCID: PMC3248284  PMID: 22182842

Results 1-2 (2)