Discordance for X-linked hypophosphataemic rickets in identical twin girls.
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.
Owen
Catherine J
CJ
Institute of Human Genetics, Centre for Life, Newcastle University, Sir James Spence Institute for Child Health, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
Habeb
Abdul
A
Pearce
Simon H S
SH
Wright
Michael
M
Ichikawa
Shoji
S
Sorenson
Andrea H
AH
Econs
Michael J
MJ
Cheetham
Tim D
TD
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004200:Diseases in Twins / Q000235:genetics; D053098:Familial Hypophosphatemic Rickets / Q000235:genetics*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D040181:Genetic Diseases, X-Linked; D006801:Humans; D007223:Infant; D008297:Male; D010375:Pedigree; D019683:Penetrance; D010710:Phosphates / Q000097:blood; D014430:Twins, Monozygotic / Q000235:genetics*
C000717427:FGF23 protein, human; D010710:Phosphates; D000089703:Fibroblast Growth Factor-23; D000469:Alkaline Phosphatase