Upon reviewing the medical history, it was found that the patient had an imperforate anus at birth, which was surgically repaired when he was 3 months old, as well as pre-axial polydactyly of both hands, which was surgically corrected when the patient was 3 years old. The patient was also reported to have exhibited mild bilateral hearing loss since the age of 5 years. However, no growth retardation or learning difficulties were reported. Physical examination revealed a dysplastic right ear with overfolded superior helices (Fig. 1A), as well as bilateral surgically corrected thumbs (Fig. 1B). Renal ultrasound examination performed on an Ultrasound LOGIQ 500 (GE Healthcare Milwaukee, WI, USA) showed bilateral small kidneys (left kidney, 74x36 mm; right kidney, 59x31 mm) with multiple cortical and medullary cysts, ranging between 10 and 17 mm (Fig. 1C). No other urinary tract structural abnormality was identified, imaging assessments did not detect any abnormalities of the liver, spleen or pancreas, and an echocardiogram was normal. The parents were clinically unaffected and no family history of genetic disease was reported.
Based on the aforementioned extra-renal features, a diagnosis of TBS was suspected. Following approval by the Ethical Committee of Shanghai XinHua Hospital according to the standards of the Declaration of Helsinki and the signed informed consent obtained from the proband, DNA was extracted from the proband's peripheral blood. SALL1 gene coding regions and splice sites were amplified and directly sequenced using an ABI PRISM 3730xl Genetic Analyzer (Applied Biosystems; Thermo Fisher Scientific, Inc., Waltham, MA, USA) as reported previously, (SALL1 sequencing primer sequences are available upon request). Sequencing analysis disclosed a novel SALL1 heterozygous nonsense mutation located in the mutational 'hotspot' of exon 2 (c.874C>T, p.Q292X; Fig. 2A), and this mutation was not present in the 100 unrelated healthy adult volunteers (all of whom provided informed consent, were free from renal disease and matched geographically) used as controls (Fig. 2B). The parents of the proband declined genetic testing, however it appears likely that this represents a de novo mutation, which is estimated to occur in ~50% of patients with TBS, as the parents of the proband are clinically healthy. It is also possible that one of the parents carries the mutation in a mosaic state, as germline mosaicism in clinically unaffected parents has been reported in TBS cases. As the patient had reached ESRF at the time of genetic diagnosis, the patient remained on maintenance hemodialysis three times per week until the final follow-up in March 2015.