@article {565,
	title = {A Patient with Berardinelli-Seip Syndrome, Novel  Splicesite Mutation and Concomitant Development of Non-diabetic Polyneuropathy},
	journal = {J Clin Res Pediatr Endocrinol},
	volume = {11},
	year = {2019},
	month = {2019 09 03},
	pages = {319-326},
	abstract = {<p>Primary polyneuropathy in the context of Seip-Berardinelli type 1 seipinopathy, or congenital generalized lipodystrophy type 1 (CGL1) has not been previously reported. We report the case history of a 27 year old female CGL1 patient presenting with an unusual additional development of non-diabetic peripheral neuropathy and learning disabilities in early adolescence. Whole exome sequencing (WES) of the patient genome identified a novel variant, homozygous for a 52 bp intronic deletion in the  locus, coding for 1-acylglycerol-3-phosphate O-acyltransferase 2, which is uniquely associated with CGL1 seipinopathies, with no molecular evidence for dual diagnosis. Functional studies using RNA isolated from patient peripheral blood leucocytes showed abnormal RNA splicing resulting in the loss of 25 amino acids from the patient AGPAT2 protein coding sequence. Stability and transcription levels for the misspliced  mRNA in our patient nonetheless remained normal. Any AGPAT2 protein produced in our patient is therefore likely to be dysfunctional. However, formal linkage of this deletion to the neuropathy observed remains to be shown. The classical clinical presentation of a patient with -associated lipodystrophy shows normal cognition and no development of polyneuropathy. Cognitive disabilities and polyneuropathy are features associated exclusively with clinical CGL type 2 arising from seipin  gene mutations. This case study suggests that in some genetic contexts,  mutations can also produce phenotypes with primary polyneuropathy.</p>},
	issn = {1308-5735},
	doi = {10.4274/jcrpe.galenos.2018.2018.0227},
	author = {Oswiecimska, Joanna and Dawidziuk, Mateusz and Gambin, Tomasz and Ziora, Katarzyna and Marek, Marta and Rzonca, Sylwia and Guilbride, D. Lys and Jhangiani, Shalini N. and Obuchowicz, Anna and Sikora, Alicja and Lupski, James R. and Wiszniewski, Wojciech and Gawlinski, Pawel}
}
@article {460,
	title = {Comprehensive genomic analysis of patients with disorders of cerebral cortical development.},
	journal = {Eur J Hum Genet},
	volume = {26},
	year = {2018},
	month = {2018 08},
	pages = {1121-1131},
	abstract = {<p>Malformations of cortical development (MCDs) manifest with structural brain anomalies that lead to neurologic sequelae, including epilepsy, cerebral palsy, developmental delay, and intellectual disability. To investigate the underlying genetic architecture of patients with disorders of cerebral cortical development, a cohort of 54 patients demonstrating neuroradiologic signs of MCDs was investigated. Individual genomes were interrogated for single-nucleotide variants (SNV) and copy number variants (CNV) with whole-exome sequencing and chromosomal microarray studies. Variation affecting known MCDs-associated genes was found in 16/54 cases, including 11 patients with SNV, 2 patients with CNV, and 3 patients with both CNV and SNV, at distinct loci. Diagnostic pathogenic SNV and potentially damaging variants of unknown significance (VUS) were identified in two groups of seven individuals each. We demonstrated that de novo variants are important among patients with MCDs as they were identified in 10/16 individuals with a molecular diagnosis. Three patients showed changes in known MCDs genes~ and a clinical phenotype beyond the usual characteristics observed, i.e., phenotypic expansion, for a particular known disease gene clinical entity. We also discovered 2 likely candidate genes, CDH4, and ASTN1, with human and animal studies supporting their roles in brain development, and 5 potential candidate genes. Our findings emphasize genetic heterogeneity of MCDs disorders and postulate potential novel candidate genes involved in cerebral cortical development.</p>},
	keywords = {Cadherins, DNA Copy Number Variations, Exome, Female, Genetic Heterogeneity, Humans, Male, Malformations of Cortical Development, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, Receptors, Cell Surface},
	issn = {1476-5438},
	doi = {10.1038/s41431-018-0137-z},
	author = {Wiszniewski, Wojciech and Gawlinski, Pawel and Gambin, Tomasz and Bekiesinska-Figatowska, Monika and Obersztyn, Ewa and Antczak-Marach, Dorota and Akdemir, Zeynep Hande Coban and Harel, Tamar and Karaca, Ender and Jurek, Marta and Sobecka, Katarzyna and Nowakowska, Beata and Kruk, Malgorzata and Terczynska, Iwona and Goszczanska-Ciuchta, Alicja and Rudzka-Dybala, Mariola and Jamroz, Ewa and Pyrkosz, Antoni and Jakubiuk-Tomaszuk, Anna and Iwanowski, Piotr and Gieruszczak-Bialek, Dorota and Piotrowicz, Malgorzata and Sasiadek, Maria and Kochanowska, Iwona and Gurda, Barbara and Steinborn, Barbara and Dawidziuk, Mateusz and Castaneda, Jennifer and Wlasienko, Pawel and Bezniakow, Natalia and Jhangiani, Shalini N and Hoffman-Zacharska, Dorota and Bal, Jerzy and Szczepanik, Elzbieta and Boerwinkle, Eric and Gibbs, Richard A and Lupski, James R}
}
