Related Experiment Video
Updated: Jun 25, 2026
Scanning Skeletal Remains for Bone Mineral Density in Forensic Contexts
Published on: January 29, 2018
Discordance for X-linked hypophosphataemic rickets in identical twin girls
Catherine J Owen1, Abdul Habeb, Simon H S Pearce
1Institute of Human Genetics, Centre for Life, Newcastle University, Sir James Spence Institute for Child Health, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
Background:
We report monozygotic twin girls with a family history consistent with X-linked hypophosphataemic rickets (XLH). One twin had a skeletal and biochemical phenotype consistent with XLH, whilst the second twin appeared normal. Complete non-penetrance in XLH has not been previously reported and our aim was to explore potential reasons for this.
Methods:
Serum and urine biochemistry were analysed at regular intervals. Microsatellite analysis was performed to confirm monozygosity and bi-parental inheritance of the X chromosome. The X chromosome inactivation pattern was studied in peripheral blood. Exons of the paternal PHEX and FGF23 genes were sequenced.
Results:
Biochemistry was persistently abnormal in the slow-growing twin 1 and normal in twin 2 who has grown normally. Maximal tubular phosphate reabsorption was 0.68 mmol/l in twin 1 and 1.64 mmol/l in twin 2 at 10.8 years of age (normal 1.15-2.58 mmol/l). Microsatellite analysis confirmed monozygosity and the X chromosome inactivation pattern was random. These studies also excluded uniparental isodisomy. The exon sequence of paternal PHEX and FGF23 genes was normal.
Conclusions:
Discordant X inactivation is a well-recognised phenomenon in identical twins, and we suspect that non-random expression of the normal PHEX gene in critical tissues is the most likely explanation for non-penetrance.
