Genetic analysis of the Gitelman syndrome coexisting with Osteogenesis imperfecta

Gitelman syndrome (GS) is an autosomal recessive disorder caused by loss-of-function mutations in SLC12A3, which encodes the Na-Cl cotransporter (NCC). Osteogenesis imperfecta (OI) is an autosomal dominant disorder caused by the inheritance of mutations mainly in the COL1A1 gene, resulting in bone fragility and deformity. In this study, we aimed to investigate the clinical and genetic manifestations in a 7-year-old boy with OI, who had electrolyte abnormalities and his four family members. Complete sequence analysis of COL1A1 revealed a novel mutation, c.268G>T, p.Glu90del. The gene mutation of OI in the patient's older brother was inherited from his mother, and the younger brother had no mutation. Two pathogenic mutations (c.179C>T, p.Thr60Met and c.1763C>T, p.Ala588Val) in SLC12A3 resulting in GS were also identified in the patient. The OI-related genetic mutation in the patient was consistent with that in the patient's mother. The GS-related genetic mutations were inherited from each parent. This study is the first to identify compound heterozygous variants in the SLC12A3 gene and a novel mutation in the COL1A1 gene in patients with OI and GS. Our findings indicate that genetic analysis is recommended to differentiate GS from BS, as clinical manifestations do not provide an accurate diagnosis.