dup(19)(q12q13.2): array-based genotype-phenotype correlation of a new possibly obesity-related syndrome

Small supernumerary marker chromosomes (sSMCs) derived from the near-centromeric area of chromosome 2 are very rare. In addition, duplications of the 2p11.2-->q11.2 region have displayed considerable variability between patients harboring and lacking clinical findings. Moreover, constitutional duplication of the 19q12-->q13.2 region has previously only been described in two cases and was associated with delay of developmental milestones, corpus callosum anomalies, and obesity. Herein, we present a genotype-phenotype correlation in a patient harboring two sSMCs derived from chromosomes 2 and 14 or 22, respectively. The DNA was studied using G-banding, fluorescence in situ hybridization techniques, and array-based comparative genomic hybridization. A 48,XX,+der(2)del(2)(p11)del(2)(q11.2),+der(14)t(14;19)(q11;q12)del(19)(q13.31) or 48,XX,+der(2)del(2)(p11)del(2)(q11.2),+der(22)t(22;19)(q11;q12)del(19)(q13.31) was detected in the patient. The sSMC 14;19 or 22;19, with its centromere originating from either chromosome 14 or 22, encompassed a 13.56 megabase (Mb) 19q derived region, harboring 263 genes, and the sSMC 2 a 2.71 Mb region including 29 genes. The patient had symptoms including a ventral septal defect, bilateral grade IV urinary reflux, corpus callosum agenesis, microphthalmia, and obesity. The 19q segment contained the genes AKT2, CEACAM1, CEBPA, LIPE, and TGFB1 which are involved in adipose tissue homeostasis and insulin resistance, and could potentially contribute to the obese phenotype observed. Array-based genetic characterization and long-term clinical evaluation with attention toward weight gain in patients with chromosome 19q duplications might in the future lead to the description of a obesity-associated genetic syndrome, something that could have implications in management and treatment of patients carrying a dup(19)(q12q13.2). Whether the der(2)(p11q11.2) contributes to the phenotype remains inconclusive.