Three novel PHEX gene mutations in four Chinese families with X-linked dominant hypophosphatemic rickets.
ABSTRACT X-linked hypophosphatemia (XLH), the most common form of inherited rickets, is a dominant disorder that is characterized by renal phosphate wasting with hypophosphatemia, abnormal bone mineralization, short stature, and rachitic manifestations. The related gene with inactivating mutations associated with XLH has been identified as PHEX, which is a phosphate-regulating gene with homologies to endopeptidases on the X chromosome. In this study, a variety of PHEX mutations were identified in four Chinese families with XLH.
We investigated four unrelated Chinese families who exhibited typical features of XLH by using PCR to analyze mutations that were then sequenced. The laboratory and radiological investigations were conducted simultaneously.
Three novel mutations were found in these four families: one frameshift mutation, c.2033dupT in exon 20, resulting in p.T679H; one nonsense mutation, c.1294A>T in exon 11, resulting in p.K432X; and one missense mutation, c.2192T>C in exon 22, resulting in p.F731S.
We found that the PHEX gene mutations were responsible for XLH in these Chinese families. Our findings are useful for understanding the genetic basis of Chinese patients with XLH.
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ABSTRACT: X-linked dominant hypophosphatemia (XLH) is the most prevalent form of inherited rickets/osteomalacia in humans. The aim of this study was to identify PHEX gene mutations and describe the clinical features observed in 6 unrelated Chinese families and 3 sporadic patients with hypophosphatemic rickets/osteomalacia.PLoS ONE 05/2014; 9(5):e97830. · 3.53 Impact Factor
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ABSTRACT: X-linked hypophosphatemia (XLH) is the most common form of familial hypophosphatemic rickets and it is caused by loss-of-function mutations in the PHEX gene. Recently, a wide variety of PHEX gene defects in XLH have been revealed; these include missense mutations, nonsense mutations, splice site mutations, insertions, and deletions. Recently, we encountered a 2-year-9-month-old female with sporadic hypophosphatemic rickets. She underwent osteotomy, dental abscess was evident, and there was severe bowing of the legs. A low serum phosphorus level in combination with elevated serum alkaline phosphatase activity and normal serum calcium is suggestive of hypophosphatemic rickets. PHEX gene analysis revealed a splice acceptor site mutation, c.934-1G>T (IVS8(-1)G>T), at the intron8 and exon9 junction. To the best of our knowledge, this mutation is novel and has not been reported. The results of this study expand and improve our understanding of the clinical and molecular characteristics and the global pool of patients with sporadic hypophosphatemic rickets.Annals of pediatric endocrinology & metabolism. 03/2014; 19(1):36-41.
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ABSTRACT: Two high resolution marine sediment cores located 83 km apart in the NE Atlantic have been studied: MD95-2006 (Barra Fan; 57°01.82 N, 10°03.48 W; 2120 m water depth) and MD04-2822 (Rockall Trough; 56°50.54 N, 11°22.96 W; 2344 m water depth). The records are anchored to the NGRIP ice core stratigraphy and GICC05 chronology by the presence of geochemically characterized Fugloyarbanki tephra and further tested by radiocarbon age control. Replicated sea surface temperature (SST) records show evidence for an abrupt and short-lived warming within Greenland Stadial (GS)-3, to which we tentatively assign an age of ca 25.6–24.8 kyr GICC05 b2k. Based on these and another marine palaeoclimate record (LINK17) from the Faroe-Shetland Channel, we propose a new three-fold event stratigraphy for GS-3 within the North East Atlantic region. The recognition of this warming event within GS-3 in NE Atlantic SST records demonstrates that such events may not readily be identified within the coldest stadials of the Greenland ice cores, highlights the need for carefully constructed event stratigraphies (independently tested by the use of tephra isochrones and radiocarbon) and illustrates pervasive millennial-scale climate variability of the North Atlantic region (Dansgaard-Oeschger (D/O) events) is deeply embedded in the dynamics of Atlantic Meridional Overturning Circulation (AMOC).Quaternary Science Reviews 03/2012; · 4.57 Impact Factor