Berardinelli-Seip syndrome patient with novel AGPAT 2 splicesite mutation and concomitant development of non-diabetic polyneuropathy Short title : New AGPAT 2 splicesite mutation with polyneuropathy

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 nondiabetic 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 AGPAT2 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 u c rr c e d p roo f