A novel heterozygous GLI2 mutation in a patient with congenital urethral stricture and renal hypoplasia/dysplasia leading to end-stage renal failure
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Glioblastoma 2 (GLI2) is a mediator of Sonic hedgehog signaling pathway that plays an important role in development of the central nervous system and limbs. Heterozygous GLI2 mutations have been associated with postaxial polydactyly, various pituitary dysfunction, and holoprosencephaly-like phenotype. Herein, we report a Japanese boy who presented with isolated growth hormone deficiency with ectopic posterior pituitary, postaxial polydactyly, atrioventricular septal defect, intellectual disability and dysmorphic facial features including mid-facial hypoplasia. The patient was also complicated with congenital urethral stricture with megacystis, hydronephrosis, and renal hypoplasia/dysplasia, which led to end-stage renal failure by the age of 8 years. Trio-whole-exome sequencing showed a novel de novo heterozygous frameshift mutation in GLI2 (c.3369delG, p.Met1123Ilefs*7) in the patient. This is the first report of possible association between GLI2 mutation and the phenotype of congenital anomalies of the kidney and urinary tract, and subsequent end-stage renal failure. Further studies on the urogenital phenotype in patients with GLI2 mutations may clarify a role of GLI2 in embryonic development of the urinary tract.
KeywordsGLI2 CAKUT Urethral stricture Renal failure Polydactyly GH deficiency
We thank the patient and their family who participated in this study. This work was supported by a Grant for the Initiative on Rare and Undiagnosed Diseases in Pediatrics (no. 15gk0110012h0101) from the Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.
Compliance with ethical standards
Conflict of interest
Yuko Hamasaki belongs to a department endowed with sponsorship by Asahi Kasei Pharma Corporation, Novartis Pharma K.K., Chugai Pharmaceutical Co., and Astellas Pharma. The other authors have declared that no Conflict of interest exists.
Human and animal rights
All procedures performed in this study involving human participants were in accordance with the ethical standards of the Institutional Review Board at Nagasaki University Graduate School of Biomedical Sciences at which the study was conducted (IRB approval number 151027331) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Written informed consent was obtained from all individual participants included in the study.
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