@article {667,
	title = {Heterozygous CTNNB1 and TBX4 variants in a patient with abnormal lung growth, pulmonary hypertension, microcephaly, and spasticity.},
	journal = {Clin Genet},
	volume = {96},
	year = {2019},
	month = {2019 Oct},
	pages = {366-370},
	abstract = {<p>The canonical wingless (Wnt) and fibroblast growth factor (FGF) signaling pathways involving CTNNB1 and TBX4, respectively, are crucial for the regulation of human development. Perturbations of these pathways and disruptions from biological homeostasis have been associated with abnormal morphogenesis of multiple organs, including the lung. The aim of this study was to identify the underlying genetic cause of abnormal lung growth, pulmonary hypertension (PAH), severe microcephaly, and muscle spasticity in a full-term newborn, who died at 4 months of age due to progressively worsening PAH and respiratory failure. Family trio exome sequencing showed a de novo heterozygous nonsense c.1603C>T (p.Arg535*) variant in CTNNB1 and a paternally inherited heterozygous missense c.1198G>A (p.Glu400Lys) variant in TBX4, both predicted to be likely deleterious. We expand the phenotypic spectrum associated with CTNNB1 and TBX4 variants and indicate that they could act synergistically to produce a distinct more severe phenotype. Our findings further support a recently proposed complex compound inheritance model in lethal lung developmental diseases and the contention that dual molecular diagnoses can parsimoniously explain blended phenotypes.</p>},
	issn = {1399-0004},
	doi = {10.1111/cge.13605},
	author = {Karolak, Justyna A and Szafranski, Przemyslaw and Kilner, David and Patel, Chirag and Scurry, Bonnie and Kinning, Esther and Chandler, Kate and Jhangiani, Shalini N and Coban Akdemir, Zeynep H and Lupski, James R and Popek, Edwina and Stankiewicz, Pawe{\l}}
}
@article {579,
	title = {Bi-allelic POLR3A Loss-of-Function Variants Cause Autosomal-Recessive Wiedemann-Rautenstrauch Syndrome.},
	journal = {Am J Hum Genet},
	volume = {103},
	year = {2018},
	month = {2018 12 06},
	pages = {968-975},
	abstract = {<p>Wiedemann-Rautenstrauch syndrome (WRS), also known as neonatal progeroid syndrome, is a rare disorder of unknown etiology. It has been proposed to be autosomal-recessive and is characterized by variable clinical features, such as intrauterine growth restriction and poor postnatal weight gain, characteristic facial features (triangular appearance to the face, convex nasal profile or pinched nose, and small mouth), widened fontanelles, pseudohydrocephalus, prominent scalp veins, lipodystrophy, and teeth abnormalities. A previous report described a single WRS patient with bi-allelic truncating and splicing variants in POLR3A. Here we present seven additional infants, children, and adults with WRS and bi-allelic truncating and/or splicing variants in POLR3A. POLR3A, the largest subunit of RNA polymerase III, is a DNA-directed RNA polymerase that transcribes many small noncoding RNAs that regulate transcription, RNA processing, and translation. Bi-allelic missense variants in POLR3A have been associated with phenotypes distinct from WRS: hypogonadotropic hypogonadism and hypomyelinating leukodystrophy with or without oligodontia. Our findings confirm the association of bi-allelic POLR3A variants with WRS, expand the clinical phenotype of WRS, and suggest specific POLR3A genotypes associated with WRS and hypomyelinating leukodystrophy.</p>},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2018.10.010},
	author = {Wambach, Jennifer A and Wegner, Daniel J and Patni, Nivedita and Kircher, Martin and Willing, Marcia C and Baldridge, Dustin and Xing, Chao and Agarwal, Anil K and Vergano, Samantha A Schrier and Patel, Chirag and Grange, Dorothy K and Kenney, Amy and Najaf, Tasnim and Nickerson, Deborah A and Bamshad, Michael J and Cole, F Sessions and Garg, Abhimanyu}
}
