@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}
}
@article {172,
	title = {Whole exome sequencing identifies de novo heterozygous CAV1 mutations associated with a novel neonatal onset lipodystrophy syndrome.},
	journal = {Am J Med Genet A},
	volume = {167A},
	year = {2015},
	month = {2015 Aug},
	pages = {1796-806},
	abstract = {<p>Despite remarkable progress in identifying causal genes for many types of genetic lipodystrophies in the last decade, the molecular basis of many extremely rare lipodystrophy patients with distinctive phenotypes remains unclear. We conducted whole exome sequencing of the parents and probands from six pedigrees with neonatal onset of generalized loss of subcutaneous fat with additional distinctive phenotypic features and report de novo heterozygous null mutations, c.424C>T (p.Q142*) and c.479_480delTT (p.F160*), in CAV1 in a 7-year-old male and a 3-year-old female of European origin, respectively. Both the patients had generalized fat loss, thin mottled skin and progeroid features at birth. The male patient had cataracts requiring extraction at age 30 months and the female patient had pulmonary arterial hypertension. Dermal fibroblasts of the female patient revealed negligible CAV1 immunofluorescence staining compared to control but there were no differences in the number and morphology of caveolae upon electron microscopy examination. Based upon the similarities in the clinical features of these two patients, previous reports of CAV1 mutations in patients with lipodystrophies and pulmonary hypertension, and similar features seen in CAV1 null mice, we conclude that these variants are the most likely cause of one subtype of neonatal onset generalized lipodystrophy syndrome.</p>},
	keywords = {Caveolin 1, Cells, Cultured, Exome, Female, Heterozygote, Humans, Infant, Newborn, Lipodystrophy, Male, Mutation, Pedigree},
	issn = {1552-4833},
	doi = {10.1002/ajmg.a.37115},
	author = {Garg, Abhimanyu and Kircher, Martin and Del Campo, Miguel and Amato, R Stephen and Agarwal, Anil K}
}
