PMC4812390_01
PMC4812390_02
(A) Right ear of the proband with overfolded superior helices. (B) Surgically corrected thumbs of the proband's hands. (C) Renal ultrasound showed multiple cysts arising from the cortex and medulla of the left and right kidneys.
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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).
Sanger sequencing electropherograms showed that (A) the proband has the SALL1 heterozygous mutation (c.874C>T, p.Q292X), (B) which was not detected in 100 healthy Chinese controls.
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f2-etm-0-0-3035
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.