@article {444,
	title = {CLCN2 chloride channel mutations in familial hyperaldosteronism type II.},
	journal = {Nat Genet},
	volume = {50},
	year = {2018},
	month = {2018 Mar},
	pages = {349-354},
	abstract = {<p>Primary aldosteronism, a common cause of severe hypertension  , features constitutive production of the adrenal steroid aldosterone. We analyzed a multiplex family with familial hyperaldosteronism type II (FH-II)  and 80 additional probands with unsolved early-onset primary aldosteronism. Eight probands had novel heterozygous variants in CLCN2, including two de novo mutations and four independent occurrences of a mutation encoding an identical p.Arg172Gln substitution; all relatives with early-onset primary aldosteronism carried the CLCN2 variant found in the proband. CLCN2 encodes a voltage-gated chloride channel expressed in adrenal glomerulosa that opens at hyperpolarized membrane potentials. Channel opening depolarizes glomerulosa cells and induces expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis. Mutant channels show gain of function, with higher open probabilities at the glomerulosa resting potential. These findings for the first time demonstrate a role of anion channels in glomerulosa membrane potential determination, aldosterone production and hypertension. They establish the cause of a substantial fraction of early-onset primary aldosteronism.</p>},
	issn = {1546-1718},
	doi = {10.1038/s41588-018-0048-5},
	author = {Scholl, Ute I and St{\"o}lting, Gabriel and Schewe, Julia and Thiel, Anne and Tan, Hua and Nelson-Williams, Carol and Vichot, Alfred A and Jin, Sheng Chih and Loring, Erin and Untiet, Verena and Yoo, Taekyeong and Choi, Jungmin and Xu, Shengxin and Wu, Aihua and Kirchner, Marieluise and Mertins, Philipp and Rump, Lars C and Onder, Ali Mirza and Gamble, Cory and McKenney, Daniel and Lash, Robert W and Jones, Deborah P and Chune, Gary and Gagliardi, Priscila and Choi, Murim and Gordon, Richard and Stowasser, Michael and Fahlke, Christoph and Lifton, Richard P}
}
@article {426,
	title = {Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands.},
	journal = {Nat Genet},
	volume = {49},
	year = {2017},
	month = {2017 Nov},
	pages = {1593-1601},
	abstract = {<p>Congenital heart disease (CHD) is the leading cause of mortality from birth defects. Here, exome sequencing of a single cohort of 2,871 CHD probands, including 2,645 parent-offspring trios, implicated rare inherited mutations in 1.8\%, including a recessive founder mutation in GDF1 accounting for \~{}5\% of severe CHD in Ashkenazim, recessive genotypes in MYH6 accounting for \~{}11\% of Shone complex, and dominant FLT4 mutations accounting for 2.3\% of Tetralogy of Fallot. De novo mutations (DNMs) accounted for 8\% of cases, including \~{}3\% of isolated CHD patients and \~{}28\% with both neurodevelopmental and extra-cardiac congenital anomalies. Seven genes surpassed thresholds for genome-wide significance, and 12 genes not previously implicated in CHD had >70\% probability of being disease related. DNMs in \~{}440 genes were inferred to contribute to CHD. Striking overlap between genes with damaging DNMs in probands with CHD and autism was also found.</p>},
	keywords = {Adult, Autistic Disorder, Cardiac Myosins, Case-Control Studies, Child, Exome, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Growth Differentiation Factor 1, Heart Defects, Congenital, Heterozygote, High-Throughput Nucleotide Sequencing, Homozygote, Humans, Male, Mutation, Myosin Heavy Chains, Pedigree, Risk, Vascular Endothelial Growth Factor Receptor-3},
	issn = {1546-1718},
	doi = {10.1038/ng.3970},
	author = {Jin, Sheng Chih and Homsy, Jason and Zaidi, Samir and Lu, Qiongshi and Morton, Sarah and DePalma, Steven R and Zeng, Xue and Qi, Hongjian and Chang, Weni and Sierant, Michael C and Hung, Wei-Chien and Haider, Shozeb and Zhang, Junhui and Knight, James and Bjornson, Robert D and Castaldi, Christopher and Tikhonoa, Irina R and Bilguvar, Kaya and Mane, Shrikant M and Sanders, Stephan J and Mital, Seema and Russell, Mark W and Gaynor, J William and Deanfield, John and Giardini, Alessandro and Porter, George A and Srivastava, Deepak and Lo, Cecelia W and Shen, Yufeng and Watkins, W Scott and Yandell, Mark and Yost, H Joseph and Tristani-Firouzi, Martin and Newburger, Jane W and Roberts, Amy E and Kim, Richard and Zhao, Hongyu and Kaltman, Jonathan R and Goldmuntz, Elizabeth and Chung, Wendy K and Seidman, Jonathan G and Gelb, Bruce D and Seidman, Christine E and Lifton, Richard P and Brueckner, Martina}
}
