ESPE Abstracts (2019) 92 P1-55

A Novel Recurrent Heterozygous Plin1 Mutation in Three Russian Patients with Partial Lipodystrophy, Dyslipidemia and Insulin Resistance

Yulia Tikhonovich1,2, Ekaterina Sorkina3, Anna Kolodkina1, Evgeniy Vasilyev1, Vasiliy Petrov1, Tatyana Pogoda1, Olga Vasiukova4, Anatoly Tiulpakov1


1Department and Laboratory of Inherited Endocrine Disorders, Moscow, Russian Federation. 2Morozovskaya Children City Clinical Hospital, Moscow, Russian Federation. 3Clamp-technologies Laboratory, Moscow, Russian Federation. 4Institute of Pediatric Endocrinology, Endocrinology Research Centre, Moscow, Russian Federation


Introduction: The PLIN1 gene encodes perilipin - a lipid droplet coat protein expressed in adipocytes where it inhibits basal and facilitates stimulated lipolysis. Mutations in PLIN1 have been described in several families with partial lipodystrophy, dyslipidemia and insulin resistance (partial lipodystrophy type 4, Familial, FPLD4). Herein we describe a novel heterozygous c.1210-1delG splicing variant in PLIN1 gene in three unrelated Russian patients with FPLD4 phenotype.

Subjects and Methods: Two girls (14 and 15 years) were referred to our clinic with suspicion of acromegaly, one girl (14 years) was referred with polydipsia, polyuria. All three patients shared similar clinical and metabolic findings: acromegalic features, loss of subcutaneous fat from extremities, excess fat depots of the face and neck, prominent muscular appearance of the calves, acanthosis nigricans, hirsutism, steatohepatitis, mild hypertension; hypertriglyceridemia and insulin resistance. 2 of 3 girls had mild diabetes mellitus. One girl had a history of recurrent pancreatitis and partial resection of the pancreas due to pancreatic necrosis. Her mother had the similar phenotype. The family histories of the two other patients were unremarkable.

Molecular genetic analysis using a custom Ion AmpliSeq next generation sequencing 'Lipodistrophy' panel and PGM sequencer (Thermo Fisher Scientific, USA) was performed in all three subjects. NGS results were confirmed by Sanger sequencing. Total RNA was isolated from subcutaneous fat obtained by a needle biopsy in one of the patients. cDNA was synthesized using random hexamer primers and PLIN1 transcripts covering exons 8-9 were amplified by PCR and sequenced.

Results: A novel heterozygous c.1210-1delG mutation in intron of PLIN1 gene was found in all three subjects. Sequencing of cDNA showed an abnormal 3' end PLIN1 transcript.

Conclusion: The novel splicing variant is predicted to result in synthesis of an aberrant C-terminal part of PLIN1 protein suggesting, similar to the previously reported cases of FPLD4, an existence of the uniform molecular mechanism in the development of this disorder.

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