CONTEXT: Congenital generalized lipodystrophy (CGL) is a rare and heterogeneous disease of autosomal recessive inheritance. Until now, no genetic findings had been reported in Chinese patients with CGL. OBJECTIVE: To analyze Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) and 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) gene variation in a Chinese boy with CGL and his family. DESIGN, SETTING, AND PARTICIPANTS: All exons of BSCL2 and AGPAT2 with adjacent intron-exon junctions were analyzed using direct sequencing. MAIN OUTCOME MEASURES: Sequences of each exon and nearby intron of the BSCL2 and AGPAT2 genes of the family members were compared with the gene bank genomic sequences. RESULTS: DNA sequence analysis of the entire coding regions and surrounding uncoding regions disclosed a novel homozygous G-->T mutation at nucleotide 909 in exon 5 of the BSCL2 gene in the affected child. A heterozygous state of the G-->T mutation of the BSCL2 gene was also found in other family members. This mutation predicts the substitution of glutamic acid at codon 189 by the stop codon (Glu189X or E189X). No variation was found in the AGPAT2 gene. Conclusion E189X is a novel BSCL2 gene mutation that contributes to CGL formation in a family of Chinese origin.
CONTEXT: Congenital generalized lipodystrophy (CGL) is a rare and heterogeneous disease of autosomal recessive inheritance. Until now, no genetic findings had been reported in Chinese patients with CGL. OBJECTIVE: To analyze Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) and 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) gene variation in a Chinese boy with CGL and his family. DESIGN, SETTING, AND PARTICIPANTS: All exons of BSCL2 and AGPAT2 with adjacent intron-exon junctions were analyzed using direct sequencing. MAIN OUTCOME MEASURES: Sequences of each exon and nearby intron of the BSCL2 and AGPAT2 genes of the family members were compared with the gene bank genomic sequences. RESULTS: DNA sequence analysis of the entire coding regions and surrounding uncoding regions disclosed a novel homozygous G-->T mutation at nucleotide 909 in exon 5 of the BSCL2 gene in the affected child. A heterozygous state of the G-->T mutation of the BSCL2 gene was also found in other family members. This mutation predicts the substitution of glutamic acid at codon 189 by the stop codon (Glu189X or E189X). No variation was found in the AGPAT2 gene. Conclusion E189X is a novel BSCL2 gene mutation that contributes to CGL formation in a family of Chinese origin.