@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}
}
