The Osteogenesis Imperfecta in the Valencia Region (Spain), 2004-2014

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder with two major subtypes, which are caused by AGPAT2 and BSCL2 mutations. Our aim was to further investigate the genetic features and clinical characteristics of infant patients with CGL.Three male infants and two female infants aged from one month to three months and unrelated with each other were involved in this study. Both whole-exome and Sanger sequencing were conducted, and variants were compared with in-house and public databases.The five infants with CGL displayed generalized lipodystrophy, skeletal muscle hypertrophy, hepatomegaly, hypertriglyceridemia, hyperinsulinemia, and liver dysfunction. Four patients (#2–5) showed more severe hypertriglyceridemia than Patient #1. A compound heterozygosity for novel frameshift mutations c.622_626delTCCTC and c.513delC in AGPAT2 was identified in Patient #1. Seven mutations in BSCL2 were found among Patients #2–5, in which splice site mutation c.404+1G > T, nonsense mutation c.402C > G, and frameshift mutation c.759_760delGA were novel. After medical treatment, metabolic parameters for all patients were under control. At the time of writing, they are seven to seventeen months old with much improved physical and cognitive development.Two novel mutations in AGPAT2 and three novel mutations in BSCL2 were identified from five unrelated infant patients diagnosed with CGL1 and CGL2.