Prenatal Diagnosis for a Novel Splice Mutation of <i>PHEX</i> Gene in a Large Han Chinese Family Affected with X-Linked Hypophosphatemic Rickets

Qiu, Guang-Rong; Liu, Caixia; Zhou, Junju; Liu, Peiyan; Wang, Jun; Jiang, Hongkun; Hou, Zhiyan; Zhao, Yanyan; Sun, Kun; Li‐Ling, Jesse

doi:10.1089/gtmb.2009.0175

Cited by 8 publications

(3 citation statements)

References 28 publications

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“…The predicted loss of the extracellular and zinc-binding domains of the mutation disrupts the overall integrity of the PHEX protein, which may lead to loss of protein function and hence leads to XLHR (Gaucher et al, 2009;Qiu et al, 2010;Kang et al, 2012). Mutation of the female patient (II:1) is thought to be a de novo mutation as none of her parents (I:1 and I:2) had any clinical evidence for HR, consistent with that de novo mutation is more frequent in females than males (Durmaz et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing

Yuan

et al. 2014

Biological Chemistry

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Familial hypophosphatemic rickets (HR), the most common inherited form of rickets, is a group of inherited renal phosphate wasting disorders characterized by growth retardation, rickets with bone deformities, osteomalacia, poor dental development, and hypophosphatemia. The purpose of this study was to identify the genetic defect responsible for familial HR in a four-generation Chinese Han pedigree by exome sequencing and Sanger sequencing. Clinical features include skeletal deformities, teeth abnormalities, hearing impairments and variable serum phosphate level in patients of this family. A novel deletion mutation, c.1553delT (p.F518Sfs*4), was identified in the X-linked phosphate regulating endopeptidase homolog gene (PHEX). The mutation is predicted to result in prematurely truncated and loss-of-function PHEX protein. Our data suggest that exome sequencing is a powerful tool to discover mutation(s) in HR, a disorder with genetic and clinical heterogeneity. The findings may also provide new insights into the cause and diagnosis of HR, and have implications for genetic counseling and clinical management.

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Section: Discussionmentioning

confidence: 99%

Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing

Yuan

et al. 2014

Biological Chemistry

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“…reported that total procedure‐related loss rate was 2.3%: 1.6% intrauterine foetal deaths within 48 h of the procedure and 0.7% spontaneous abortions in the 2 weeks following the procedure . However, there is almost no procedure‐related abortion and foetal death in Chinese study and previous studies have shown that prenatal diagnosis by percutaneous umbilical blood sampling is safe . Moreover, it would provide us with the neutrophils needed for the DHR analysis.…”

Section: Discussionmentioning

confidence: 89%

Prenatal Diagnosis of X‐Linked Chronic Granulomatous Disease by Percutaneous Umbilical Blood Sampling

et al. 2012

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In this study, we investigated how to prenatally diagnose X-linked chronic granulomatous disease (X-CGD) effectively and accurately. Percutaneous umbilical blood sampling was conducted in the 22nd week of pregnancy. NADPH oxidase activity and gp91 phox protein expression of neutrophils were analysed using flow cytometry. Direct sequencing was used to detect CYBB gene mutations. Umbilical blood was obtained from seven foetuses whose mothers were X-CGD carriers. Six foetuses, whose mothers needed prenatal diagnosis because of other diseases, were used as control. The neutrophils in all 13 foetuses showed lower hydrogen peroxide generation (stimulation index < 100) and gp91 phox protein expression. Among the seven foetuses whose mothers were X-CGD carriers, four foetuses (Family 2, 4, 5 and 7) had CYBB gene mutations and showed very low hydrogen peroxide generation (stimulation index < 10) and no gp91 phox expression. The other three foetuses (Family 1, 3 and 6) had no CYBB gene mutations and showed stimulation index of 20-50 and partial or normal gp91 phox protein expression (no difference with controls). Two of the three mothers (Family 1 and 3) have delivered healthy infants with normal hydrogen peroxide generation and expression of gp91 phox in neutrophils. Combined with direct sequencing, dihydrorhodamine oxidation analysis and gp91 phox protein detection is an effective and accurate method for prenatal screening for X-CGD.

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“…According to the PHEX mutation database, the frequencies of the different types of mutations include the following: 27% frameshifts, 19.8% abnormal splicing, 19.4% missense, 18% nonsense, 28% deletions, and 2.4% polymorphisms. However, only 14 mutations (2 deletion mutation, 3 nonsense mutations, 1 frameshift mutation, 3 donor splice site mutations, and 5 missense mutations) in the PHEX gene have been reported in Chinese patients with familial XLH [15]–[20]. In this study, we identified PHEX gene mutations in Chinese patients (familial and sporadic) with hypophosphatemic rickets/osteomalacia in order to elucidate the PHEX gene mutation types and clinical features observed in Chinese patients.…”

Section: Introductionmentioning

confidence: 99%

Identification of Two Novel Mutations in the PHEX Gene in Chinese Patients with Hypophosphatemic Rickets/Osteomalacia

Yue

et al. 2014

PLoS ONE

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ObjectiveX-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.MethodsFor this study, 45 individuals from 9 unrelated families of Chinese Han ethnicity (including 16 patients and 29 normal phenotype subjects), and 250 healthy donors were recruited. All 22 exons and exon-intron boundaries of the PHEX gene were amplified by polymerase chain reaction (PCR) and directly sequenced.ResultsThe PHEX mutations were detected in 6 familial and 3 sporadic hypophosphatemic rickets/osteomalacia. Altogether, 2 novel mutations were detected: 1 missense mutation c.1183G>C in exon 11, resulting in p.Gly395Arg and 1 missense mutation c.1751A>C in exon 17, resulting in p.His584Pro. No mutations were found in the 250 healthy controls.ConclusionsOur study increases knowledge of the PHEX gene mutation types and clinical phenotypes found in Chinese patients with XLH, which is important for understanding the genetic basis of XLH. The molecular diagnosis of a PHEX genetic mutation is of great importance for confirming the clinical diagnosis of XLH, conducting genetic counseling, and facilitating prenatal intervention, especially in the case of sporadic patients.

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Prenatal Diagnosis for a Novel Splice Mutation of PHEX Gene in a Large Han Chinese Family Affected with X-Linked Hypophosphatemic Rickets

Abstract: A novel splice mutation c.849+1G>A in the PHEX gene is responsible for XLH in the studied family. Further studies may enhance our understanding of the role of this mutation in the pathogenesis of XLH.

Cited by 8 publications

References 28 publications

Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing

Identification of a novel PHEX mutation in a Chinese family with X-linked hypophosphatemic rickets using exome sequencing

Prenatal Diagnosis of X‐Linked Chronic Granulomatous Disease by Percutaneous Umbilical Blood Sampling

Identification of Two Novel Mutations in the PHEX Gene in Chinese Patients with Hypophosphatemic Rickets/Osteomalacia

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