Targeted massively parallel sequencing for congenital generalized lipodystrophy

Author(s)

Aline D. Costa-Riquetto ^[1] ; Lucas S. Santana ^[2] ; Lílian A. Caetano ^[3] ; Antônio M. Lerário ; Joya E. M. Correia-Deur ^[5] ; Débora R. Bertola ^[6] ; Chong A. Kim ^[7] ; Márcia Nery ^[8] ; Alexander A. L. Jorge ^[9] ; Milena G. Teles ^[10]

Affiliation

^[1] Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas - Brasil

^[2] Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas - Brasil

^[3] Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas - Brasil

^[5] Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas - Brasil

^[6] Universidade de São Paulo. Instituto da Criança. Unidade de Genética - Brasil

^[7] Universidade de São Paulo. Instituto da Criança. Unidade de Genética - Brasil

^[8] Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas - Brasil

^[9] Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas - Brasil

^[10] Universidade de São Paulo. Faculdade de Medicina. Hospital das Clínicas - Brasil

• Document type: Journal article
• Source: ARCHIVES OF ENDOCRINOLOGY METABOLISM; v. 64, n. 5, p. 559-566, 2020-08-28.

Abstract

ABSTRACT Objective: Our aim is to establish genetic diagnosis of congenital generalized lipodystrophy (CGL) using targeted massively parallel sequencing (MPS), also known as next-generation sequencing (NGS). Subjects and methods: Nine unrelated individuals with a clinical diagnosis of CGL were recruited. We used a customized panel to capture genes related to genetic lipodystrophies. DNA libraries were generated, sequenced using the Illumina MiSeq, and bioinformatics analysis was performed. Results: An accurate genetic diagnosis was stated for all nine patients. Four had pathogenic variants in AGPAT2 and three in BSCL2. Three large homozygous deletions in AGPAT2 were identified by copy-number variant analysis. Conclusions: Although we have found allelic variants in only 2 genes related to CGL, the panel was able to identify different variants including deletions that would have been missed by Sanger sequencing. We believe that MPS is a valuable tool for the genetic diagnosis of multi-genes related diseases, including CGL. (AU)

• FAPESP's process: 13/03236-5 - New approaches and methodologies in molecular-genetic studies of growth and pubertal development disorders
• Grantee: Alexander Augusto de Lima Jorge
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/19920-2 - Next-generation sequencing analysis of patients with clinical diagnosis of MODY (maturity onset diabetes of the young)
• Grantee: Milena Gurgel Teles Bezerra
• Support Opportunities: Regular Research Grants