Berardinelli-Seip syndrome patient with novel splicesite mutation and concomitant development of non-diabetic polyneuropathy

TitleBerardinelli-Seip syndrome patient with novel splicesite mutation and concomitant development of non-diabetic polyneuropathy
Publication TypeJournal Article
Year of Publication2018
AuthorsOswiecimska, J, Dawidziuk, M, Gambin, T, Ziora, K, Marek, M, Rzonca, S, D. Guilbride, L, Jhangiani, SN, Obuchowicz, A, Sikora, A, Lupski, JR, Wiszniewski, W, Gawlinski, P
JournalJ Clin Res Pediatr Endocrinol
Date Published2018 Dec 19
ISSN1308-5735
Abstract

Primary polyneuropathy in the context of Seip-Berardinelli type 1 seipinopathy, or congenital lipodystrophy type 1 (CGL1) is previously unknown. We report the case history of a 27 year old female CGL1 patient presenting with unusual additional development of non-diabetic peripheral neuropathy (PN) and learning disabilities in early adolescence. Whole exome sequencing (WES) of the patient genome identifies a novel rare variant homozygous for a 52 bp intronic deletion in the locus uniquely associated with CGL1 seipinopathies, with no molecular evidence for dual diagnosis. Functional studies using RNA isolated from patient peripheral blood leucocytes show abnormal RNA splicing resulting in the loss of 25 amino acids from patient protein coding sequence. Stability and transcription levels for the misspliced mRNA in our patient nonetheless remain normal. Any 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 to date associated exclusively with clinical CGL type 2 arising from gene mutations. This case study suggests that in some genetic contexts, mutations can also produce phenotypes with primary polyneuropathy.

DOI10.4274/jcrpe.0227
Alternate JournalJ Clin Res Pediatr Endocrinol
PubMed ID30563316