Owen Catherine J, Habeb Abdul, Pearce Simon H S, Wright Michael, Ichikawa Shoji, Sorenson Andrea H, Econs Michael J, Cheetham Tim D
Institute of Human Genetics, Centre for Life, Newcastle University, Sir James Spence Institute for Child Health, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
Horm Res. 2009;71(4):237-44. doi: 10.1159/000201113. Epub 2009 Mar 4.
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.
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.
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.
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.
我们报告了一对单卵双胞胎女孩，她们的家族史与X连锁低磷性佝偻病（XLH）相符。其中一个双胞胎具有与XLH一致的骨骼和生化表型，而另一个双胞胎看起来正常。XLH完全不发病此前尚未见报道，我们的目的是探究其潜在原因。
定期分析血清和尿液生化指标。进行微卫星分析以确认单卵性和X染色体的双亲遗传。研究外周血中的X染色体失活模式。对父源PHEX和FGF23基因的外显子进行测序。
生长缓慢的双胞胎1的生化指标持续异常，而生长正常的双胞胎2的生化指标正常。10.8岁时，双胞胎1的最大肾小管磷重吸收为0.68 mmol/l，双胞胎2为1.64 mmol/l（正常范围为1.15 - 2.58 mmol/l）。微卫星分析确认了单卵性，且X染色体失活模式是随机的。这些研究也排除了单亲二体。父源PHEX和FGF23基因的外显子序列正常。
不一致的X失活是同卵双胞胎中一种公认的现象，我们怀疑关键组织中正常PHEX基因的非随机表达是不发病最可能的解释。
