Genetic analysis of a case of mild epilepsy due to variant of SCN9A gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a patient with epilepsy and provide genetic counseling.@*METHODS@#A patient who had visited the Center for Reproductive Medicine of Shandong University on November 11, 2020 was selected as the study subject, and her clinic information was collected. Candidate variant was identified through whole exome sequencing (WES), and Sanger sequencing was used for validation. Possible transcriptional changes caused by the variant was detected by reverse transcription-PCR and Sanger sequencing.@*RESULTS@#The patient was a 35-year-old female with no fever at the onset, loss of consciousness and abnormal firing in the temporal lobe, manifesting predominantly as convulsions and fainting. WES revealed that she had harbored a heterozygous c.2841+5G>A variant of the SCN9A gene, which was verified by Sanger sequencing. cDNA sequencing confirmed that 154 bases were inserted between exons 16 and 17 of the SCN9A gene, which probably produced a truncated protein and affected the normal function of the SCN9A protein. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.2841+5G>A variant was classified as likely pathogenic (PVS1_Strong+PM2_Supporting).@*CONCLUSION@#The c.2841+5G>A variant of the SCN9A gene probably underlay the epilepsy in this patient. Above finding has enriched the variant spectrum of the SCN9A gene and provided a basis for the prenatal diagnosis and preimplantation genetic testing for this patient.

Association between maternal gestational diabetes mellitus and the risk of autism spectrum disorder in offspring / 中国当代儿科杂志

OBJECTIVES@#To explore the association between maternal gestational diabetes mellitus (GDM) exposure and the development of autism spectrum disorder (ASD) in offspring.@*METHODS@#A case-control study was conducted, recruiting 221 children with ASD and 400 healthy children as controls. Questionnaires and interviews were used to collect information on general characteristics of the children, socio-economic characteristics of the family, maternal pregnancy history, and maternal disease exposure during pregnancy. Multivariate logistic regression analysis was used to investigate the association between maternal GDM exposure and the development of ASD in offspring. The potential interaction between offspring gender and maternal GDM exposure on the development of ASD in offspring was explored.@*RESULTS@#The proportion of maternal GDM was significantly higher in the ASD group compared to the control group (16.3% vs 9.4%, P=0.014). After adjusting for variables such as gender, gestational age, mode of delivery, parity, and maternal education level, maternal GDM exposure was a risk factor for ASD in offspring (OR=2.18, 95%CI: 1.04-4.54, P=0.038). On the basis of adjusting the above variables, after further adjusting the variables including prenatal intake of multivitamins, folic acid intake in the first three months of pregnancy, and assisted reproduction the result trend did not change, but no statistical significance was observed (OR=1.94, 95%CI: 0.74-5.11, P=0.183). There was an interaction between maternal GDM exposure and offspring gender on the development of ASD in offspring (P<0.001). Gender stratified analysis showed that only in male offspring of mothers with GDM, the risk of ASD was significantly increased (OR=3.67, 95%CI: 1.16-11.65, P=0.027).@*CONCLUSIONS@#Maternal GDM exposure might increase the risk of ASD in offspring. There is an interaction between GDM exposure and offspring gender in the development of ASD in offspring.

Ultrawide-range radiation detection based on dynamic identification and analysis of the response of a monolithic active pixel sensor.

In this paper, we present an ultrawide-range radiation detection method based on dynamic recognition and analysis of the response signal of a monolithic active pixel sensor (MAPS). Our analysis of the MAPS response mechanism determined that adaptive adjustment of the sensor's integral time is key to quantification of ionizing radiation in an ultrawide range. We also determined that different data processing methods are required for accurate quantification of high and low radiation dose rates. The results of experiments conducted after calibration demonstrate that our technique is capable of radiation detection across five orders of magnitude (ranging from milligrays per hour to hundreds of grays per hour), with errors of less than 5%. Chip-based nuclear radiation detection can be realized using our technique, enabling MAPS to be used as a supplement to traditional detectors in characterization of unknown and complex radiation environments.

Clinical analysis of nonsyndromic cleft lip and palate in 109 patients living at high altitude / 中国基层医药

Objective:To analyze the risk factors and characteristics of nonsyndromic clef lip and palate living at high altitude, providing evidence for preventing cleft lip and palate.Methods:The clinical data of 109 Tibetan patients with nonsyndromic cleft lip and palate who received treatment in People's Hospital of Ganzi Tibetan Autonomous Prefecture between August 2016 and August 2020 were retrospectively analyzed.Results:The 109 patients with cleft lip and palate were aged 4 months to 48 years. The ratio of male to female patients was 1.42∶1. The ratio of male to female patients with simple cleft lip was 1.40∶1. The ratio of male to female patients with cleft lip and palate was 1.71∶1. The ratio of male to female patients with simple cleft palate was 1.3∶1. The mothers of all patients did not undergo prenatal examination and did not take folic acid during pregnancy. Eight patients (7.3%) had a family genetic history of cleft lip and palate. Two patients (1.8%) had consanguineous marriage within three generations. Seven patients (6.4%) took drugs in the first three months of pregnancy. One patient (0.9%) had malnutrition during pregnancy. Among 65 patients (59.1%) had simple cleft lip, 48 patients (73.8%) had incomplete cleft lip. Among 25 patients (22.9%) had simple cleft palate, 14 patients (56.0%) had incomplete cleft palate. Nineteen patients (17.2%) had cleft lip and palate. The number of patients with unilateral cleft lip with or without cleft palate was greater than that of patients with bilateral cleft lip with or without cleft palate. The number of patients with left cleft lip with or without cleft palate was greater than that of patients with right cleft lip with or without cleft palate. The ratio of the number of patients with unilateral cleft lip to the number of patients with bilateral cleft lip was 12∶1. The ratio of the number of patients with left cleft lip to the number of patients with right cleft lip was 1.9∶1. The ratio of the number of patients with unilateral cleft lip and palate to the number of patients with bilateral cleft lip and palate was 5.3∶1. The ratio of the number of patients with left cleft lip and palate to the number of patients with right cleft lip and palate was 2.8∶1. Twelve patients (63.2%) had complete cleft palate.Conclusion:Popularizing knowledge of pregnancy health care and strengthening pre-pregnancy and during-pregnancy examination can reduce the incidence of cleft lip and palate.

WU Xu's experience of sequential therapy for peripheral facial paralysis / 中国针灸

The paper introduces professor WU Xu 's experience of sequential therapy for peripheral facial paralysis. The sequential therapy refers to a staging treatment, but not rigidly adheres to it. With this therapy, the acupuncture- moxibustion regimen is modified flexibly in line with the specific symptoms of illness. At the acute phase of peripheral facial paralysis, warm acupuncture at Wangu (GB 12) is predominated and electroacupuncture is not recommended at the acupoints on the face. At the recovery phase, warm acupuncture at Zusanli (ST 36) is the main therapy and electroacupuncture is applied to the acupoints on the face appropriately. Besides, for the intractable case, the tapping technique with plum-blossom needle or skin needle should be combined and exerted in the local affected region. At the sequelae phase, in order to shorten the duration of illness, depending on the different types of facial paralysis, i.e. stiffness type, spasmodic type and flaccid type, the corresponding needling techniques are provided, i.e. bloodletting and moxibustion, strong stimulation with contralateral acupuncture and the technique for promoting the governor vessel and warming up yang.

Research advances in the formation mechanism of primary intrahepatic stones caused by biliary flora / 临床肝胆病杂志

Primary intrahepatic stones (PIS) is a refractory disease with a high incidence rate in southwest China, and some patients still require surgery again or even more times after initial treatment. Many studies in recent years have shown that some specific flora can colonize in the intrahepatic bile duct, leading to chronic infection and inflammation of the biliary system, and these specific types of flora, called "stone-causing flora", can produce metabolites such as β-glucuronidase and play an important role in the formation of pigmented stones. This article analyzes the role of stone-causing flora in the pathogenesis of PIS, so as to provide more treatment options for PIS patients.

Latent classes of health risk behaviors in medical students and depressive symptoms / 中国学校卫生

Objective@#To identify the latent classes of various health risk behaviors among medical students and further analyze the correlation between different classes and depression.@*Methods@#Using the method of convenient sampling, 2 014 medical students were selected from Anhui Medical University in October 2018. Self-designed online questionnaire were used to collect demographic data, health risk behavior (including smoking, drinking, suicide, sleep disorders, mobile phone dependence and lack of exercise) and depressive symptoms. Latent Class Analysis was used to cluster individuals. Logistic regression was provided to further analyze the association between health risk behaviors and depressive symptoms for the groups.@*Results@#The health hazard behaviors of medical students could be divided into three separate classes: substance dependence group (8.4%), mobile phone dependence group (22.4%) and low-risk group (69.2%). The distribution of health risk behaviors of medical students with different gender, major, grade, only child，father s educational level，monthly living expenses, academic achievement and number of friends were statistically significant (χ 2=99.37,19.07,12.05,6.64,14.28,19.35,20.61,26.39,P<0.05). The results of Logistic regression analysis showed that after adjusting for gender, major, grade, only child, father s educational level，monthly living expenses, academic achievement and number of friends, the mobile phone dependence group was positively correlated with depressive symptoms (β=1.75, P<0.01).@*Conclusion@#Different ratent classes of health risk behaviors have different correlation with depressive symptoms in groups.It is suggested that school health workers should make individualized intervention plan for different types of health hazard behavior of medical students in the future educational activities, carry out stratified intervention, alleviate the symptoms of depression and promote the mental health of medical students.

Efficacy and safety of dual versus mono antiplatelet therapy in patients with stroke or transient ischemic attack: An updated meta-analysis of 18 randomized controlled trials.

The optimal duration of dual antiplatelet therapy (DAPT) as a routine treatment in stroke patients is still controversial. The efficacy and safety of DAPT may vary with different regiments, initiating treatment time and race. Our study assessed the efficacy and safety of DAPT in patients with stroke and to determine the factors influencing the efficacy and safety of DAPT. Relevant studies published up to May 2019 from PubMed, Embase, Web of Science and the Cochrane Library. Randomized controlled trials comparing DAPT with mono antiplatelet therapy (MAPT) for stroke secondary prevention were included. The primary endpoints were stroke recurrence, ischemic stroke recurrence and all-cause death. Subgroup analysis was made according to regiment, initiating treatment time and race. Eighteen studies (n=33353) were included. Comparing with MAPT, short-term DAPT reduced stroke recurrence (RR = 0.68, 95% CI = 0.60-0.77) and ischemic stroke recurrence (RR = 0.67, 95% CI = 0.59-0.77) but increased major bleeding (RR = 1.82, 95% CI = 1.11-2.98). Long-term DAPT had no superiority compared with MAPT. Aspirin plus clopidogrel comparing with aspirin and early initiating treatment time comparing with MAPT decreased stroke recurrence (RR = 0.74, 95% CI = 0.67-0.83; RR = 0.69, 95% CI = 0.61-0.78) and ischemic stroke recurrence ( RR = 0.71, 95% CI = 0.64-0.79; RR = 0.68, 95% CI = 0.59-0.77) but also increased major bleeding (RR = 1.70, 95% CI = 1.38-2.09; RR = 1.75, 95% CI = 1.07-2.85). DAPT reduced stroke and ischemic stroke recurrence in non-Asian group but only reduced ischemic stroke recurrence in Asian group. As stroke secondary prevention, short-term DAPT rather than long-term DAPT could be a better choice. Patients could benefit more from aspirin plus clopidogrel or given DAPT within 72 h after symptoms onset. Race may be a factor influencing the efficacy of DAPT.

Prevalence and Multilocus Genotyping of Giardia lamblia in Cattle in Jiangxi Province, China: Novel Assemblage E Subtypes Identified

Giardia lamblia is a common enteric pathogen associated with diarrheal diseases. There are some reports of G. lamblia infection among different breeds of cattle in recent years worldwide. However, it is yet to know whether cattle in Jiangxi province, southeastern China is infected with G. lamblia. The objectives of the present study were to investigate the prevalence and examine the multilocus genotypes of G. lamblia in cattle in Jiangxi province. A total of 556 fecal samples were collected from 3 cattle breeds (dairy cattle, beef cattle, and buffalo) in Jiangxi province, and the prevalence and genotypes of G. lamblia were determined by the nested PCR amplification of the beta-giardin (bg) gene. A total of 52 samples (9.2%) were positive for G. lamblia. The highest prevalence of G. lamblia was detected in dairy cattle (20.0%), followed by that in beef cattle (6.4%), and meat buffalo (0.9%). Multilocus sequence typing of G. lamblia was performed based on sequences of the bg, triose phosphate isomerase and glutamate dehydrogenase loci, and 22, 42, and 52 samples were amplifiable, respectively, forming 15 MLGs. Moreover, one mixed G. lamblia infection (assemblages A and E) was found in the present study. Altogether, 6 novel assemblage E subtypes (E41*-E46*) were identified for the first time. These results not only provided baseline data for the control of G. lamblia infection in cattle in this southeastern province of China, but also enriched the molecular epidemiological data and genetic diversity of G. lamblia in cattle.

Identification of a novel splicing variant of IDS gene in a pedigree affected with type II glycosaminoglycan product storage disease / 中华医学遗传学杂志

OBJECTIVE@#To analyze variant of IDS gene in a pedigree affected with mucopolysaccharidosis type II (MPS II).@*METHODS@#The proband was subjected to next generation sequencing and Sanger sequencing to identify potential variants. Suspected variant was analyzed by its co-segregation with the disease in the pedigree. Its impact on mRNA splicing was analyzed by using reverse transcription PCR (RT-PCR).@*RESULTS@#A hemizygous IVS1-3T>G variant was found in the IDS gene in the proband. RT-PCR results revealed two abnormal cDNA fragments of 600 bp and 300 bp. The 600 bp fragment had inserted 216 nucleotides at the 3' end of intron 1, while the 300 bp fragment had lost 109 nucleotides at the 5' end of exon 2, which resulted in two truncated proteins comprising 38 and 92 amino acids, respectively, instead of the normal product (550 amino acids). The proband and his mother were respectively hemizygous and heterozygous for the variant. The same variant was not found among 100 normal controls.@*CONCLUSION@#The IVS1-3T>G variant of the IDS gene probably underlies the MPS II in this pedigree by causing reduction or elimination of the IDS protein.

Identification of a novel variant of COL4A5 gene in a pedigree affected with Alport syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a pedigree affected with Alport syndrome.@*METHODS@#Next generation sequencing and Sanger sequencing was carried out to detect potential variant of the COL4A5 gene among members from the pedigree and 100 unrelated healthy controls.@*RESULTS@#A novel missense c.3293G>T (p.Gly1098Val) variant was found in the COL4A5 gene among 6 affected members but not the unaffected members of the pedigree or the 100 healthy controls. According to the American College of Medical Genetics and Genomics standards and guidelines, the c.3293G>T variant was classified as pathogenic (PP1-strong+PM1+PM2+PP3+PP4).@*CONCLUSION@#By destructing the Gly-X-Y structure of its protein product, the c.3293G>T variant of the COL4A5 gene probably underlies the Alport syndrome in this pedigree. Above finding has enriched the spectrum of COL4A5 variants.

Prevalence and Multilocus Genotyping of Giardia lamblia in Cattle in Jiangxi Province, China: Novel Assemblage E Subtypes Identified

Giardia lamblia is a common enteric pathogen associated with diarrheal diseases. There are some reports of G. lamblia infection among different breeds of cattle in recent years worldwide. However, it is yet to know whether cattle in Jiangxi province, southeastern China is infected with G. lamblia. The objectives of the present study were to investigate the prevalence and examine the multilocus genotypes of G. lamblia in cattle in Jiangxi province. A total of 556 fecal samples were collected from 3 cattle breeds (dairy cattle, beef cattle, and buffalo) in Jiangxi province, and the prevalence and genotypes of G. lamblia were determined by the nested PCR amplification of the beta-giardin (bg) gene. A total of 52 samples (9.2%) were positive for G. lamblia. The highest prevalence of G. lamblia was detected in dairy cattle (20.0%), followed by that in beef cattle (6.4%), and meat buffalo (0.9%). Multilocus sequence typing of G. lamblia was performed based on sequences of the bg, triose phosphate isomerase and glutamate dehydrogenase loci, and 22, 42, and 52 samples were amplifiable, respectively, forming 15 MLGs. Moreover, one mixed G. lamblia infection (assemblages A and E) was found in the present study. Altogether, 6 novel assemblage E subtypes (E41*-E46*) were identified for the first time. These results not only provided baseline data for the control of G. lamblia infection in cattle in this southeastern province of China, but also enriched the molecular epidemiological data and genetic diversity of G. lamblia in cattle.

Clinical analysis on death cases of visceral leishmaniasis / 中国感染控制杂志

Objective To understand the clinical characteristics and changes in laboratory indicators of patients died of visceral leishmaniasis (VL).Methods Clinical data of 4 patients died of VL in Beijing Friendship Hospital from January 2013 to June 2018 were analyzed, differences in laboratory indicators were compared.Results Disease course of 4 cases of VL ranged from3 to 12 months, all patients had multiple organ damage, including 3 cases with hepatomegaly and splenomegaly, 2 cases with central nervous system damage.IgG antibodies of leishmania were positive in 4 patients, Leishman-Donovan body was found in bone marrow smears.Routine peripheral blood test results in 4 patients decreased significantly, albumin decreased significantly and globulin increased;level of serum sodium ion in 4 patients was lower than 135 mmol/L.Conclusion Long disease course, multiple organ damage, involvement of central nervous system, significant reducing in peripheral blood routine test results, hypoproteinemia, and hyponatremia in patients with VL all indicate poor prognosis and high mortality.

Novel mutations of XPC gene detected in a family affected with xeroderma pigmentosum group C / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect mutations of the XPC (XPC complex subunit, DNA damage recognition and repair factor) gene in a family affected with xeroderma pigmentosum group C (XP-C).</p><p><b>METHODS</b>The patient was subjected to next-generation sequencing and Sanger sequencing. Suspected mutations were validated by Sanger sequencing. Effect of splicing mutation was confirmed by reverse transcription-PCR (RT-PCR).</p><p><b>RESULTS</b>Compound heterozygous mutations of c.2098G to T and c.2034-7_2040del were found in the XPC gene in the proband. Among these, c.2098G to T (p.G700X) is a nonsense mutation resulting in a truncated XPC protein. C.2034-7_2040del involves the -1 position, which may alter the splice donor site of the intron 11 of XPC and result in a truncated XPC protein with loss of amino acids from 940 to 679 positions. The two mutations were not detected among 100 unrelated healthy controls.</p><p><b>CONCLUSION</b>Mutations of c.2098 G to T and c.2034-7_2040del of the XPC gene may lead to abnormal XPC expression and reduction or elimination of normal XPC functions, which may underlie the disease in this family.</p>

Application of droplet digital PCR for non-invasive prenatal diagnosis of single gene disease in two families / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the value of droplet digital PCR (ddPCR) for non-invasive prenatal diagnosis of single gene disease in two families.</p><p><b>METHODS</b>Paternal mutation in cell-free DNA derived from the maternal blood and amniotic fluid DNA was detected by ddPCR. Suspected mutation in the amniotic fluid DNA was verified with Sanger sequencing.</p><p><b>RESULTS</b>The result of ddPCR and Sanger sequencing indicated that the fetuses have carried pathogenic mutations from the paternal side in both families.</p><p><b>CONCLUSION</b>Droplet digital PCR can accurately detect paternal mutation carried by the fetus, and it is sensitive and reliable for analyzing trace samples. This method may be applied for the diagnosis of single gene diseases caused by paternal mutation using peripheral blood sample derived from the mother.</p>

Advances on anti-neoplastic STAT3 inhibitors / 药学学报

Signal transducer and activator of transcription 3 (STAT3) is a kind of signal transduction protein involved in cell proliferation, differentiation, apoptosis and other important physiological processes in response to a large number of cytokines and growth factors in cells. It has been shown that constitutive activation of STAT3 is closely associated with oncogenesis and tumorigenesis. Inhibition of aberrant STAT3 signaling has been one of promising strategies for the development of anti-neoplastic therapeutics. The review summarizes the latest progress of STAT3 inhibitors in recent years from the perspective of targeting N-terminal domain, DNA binding domain, SH2 domain and C-terminal transactivation domain of STAT3.

[Clinical features of imported schistosomiasis mansoni in Beijing City：a report of 6 cases].

OBJECTIVE: To analyze the clinical features of 6 patients with imported schistosomiasis mansoni, including the epidemic history, clinical manifestations, laboratory tests and therapeutic effect, so as to provide references for improving the levels of diagnosis and treatment of physicians. METHODS: The clinical data of 6 patients with imported schistosomiasis mansoni from January 2009 to July 2016 were collected and analyzed. RESULTS: All the 6 imported patients with schistosomiasis mansoni had a clear history of cercarial infested water exposure. The main manifestations were continuous fever and eosinophilia. Three (50%) patients were accompanied with diarrhea. Anti-Schistosoma japonicum IgG antibody were cross positive in 2 (33.3%) patients, while live eggs of S. mansoni were explored in intestinal mucosa specimens of all the patients. CD3+CD8+ T cell ratio was decreased significantly but B cell ratio was elevated in all the patients, and the main immunoglobulin of the patients was IgG. Hydroperitoneum and splenomegaly signs were discovered by abdominal ultrasonography in 16.6% (1/6) of the patients. Multiple liver nodules and wall thickening of rectum and sigmoid colon were revealed by pelvic MR scan in 16.6% (1/6) of the patients. Colitis was found in all the patients, and 66.6% (4/6) of the patients were combined with multiple colonic ulcers by the electronic colonoscopy examination. Chronic inflammation and eosinophil infiltration were found in all the patients by rectum pathology. All 6 patients were cured with chemotherapy named praziquantel. CONCLUSIONS: Comprehensive analysis of clinical data including epidemiological history, specific manifestations, laboratory tests and intestinal mucosa pathology may be benefit of the management of schistosomiasis mansoni.

Clinical features of imported schistosomiasis mansoni in Beijing City:a re-port of 6 cases / 中国血吸虫病防治杂志

Objective To analyze the clinical features of 6 patients with imported schistosomiasis mansoni,including the epidemic history,clinical manifestations,laboratory tests and therapeutic effect,so as to provide references for improving the levels of diagnosis and treatment of physicians. Methods The clinical data of 6 patients with imported schistosomiasis mansoni from January 2009 to July 2016 were collected and analyzed. Results All the 6 imported patients with schistosomiasis mansoni had a clear history of cercarial infested water exposure. The main manifestations were continuous fever and eosinophilia. Three (50%)patients were accompanied with diarrhea. Anti-Schistosoma japonicum IgG antibody were cross positive in 2(33.3%)pa-tients,while live eggs of S. mansoni were explored in intestinal mucosa specimens of all the patients. CD3+CD8+T cell ratio was decreased significantly but B cell ratio was elevated in all the patients,and the main immunoglobulin of the patients was IgG. Hydroperitoneum and splenomegaly signs were discovered by abdominal ultrasonography in 16.6%(1/6)of the patients. Multi-ple liver nodules and wall thickening of rectum and sigmoid colon were revealed by pelvic MR scan in 16.6%(1/6)of the pa-tients. Colitis was found in all the patients,and 66.6%(4/6)of the patients were combined with multiple colonic ulcers by the electronic colonoscopy examination. Chronic inflammation and eosinophil infiltration were found in all the patients by rectum pa-thology. All 6 patients were cured with chemotherapy named praziquantel. Conclusion Comprehensive analysis of clinical data including epidemiological history,specific manifestations,laboratory tests and intestinal mucosa pathology may be benefit of the management of schistosomiasis mansoni.

The application study of real-time feedback teaching in the interviewer training for practical skills examination of doctor's qualification / 中华医学教育探索杂志

To study the effect of real-time feedback teaching in the interviewer training for practical skills examination of doctor's qualification. The process of real-time feedback teaching included: prepara-tion; on-site teaching; on-site training; evaluation of the training effect. The manifestation of the trained in-terviewers was evaluated after the training of physical examination and practical operation, and the inter-viewers' accuracy was improved in both physical examination group and practical operation group. Therefore, it can be concluded that the application of real-time feedback teaching in the interviewer training for prac-tical skills examination of doctor's qualification is effective, and is worth popularizing.

Identification of a novel splicing mutation of PHEX gene in a pedigree affected with X-linked hypophosphatemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify potential mutation of PHEX gene in two patients from a family affected with X-linked hypophosphatemia (XLH).</p><p><b>METHODS</b>PCR and Sanger sequencing were performed on blood samples from the patients and 100 healthy controls. Reverse transcription-PCR (RT-PCR) was used to determine the mRNA expression in patient samples.</p><p><b>RESULTS</b>A splicing site mutation, IVS21+2T>G, was found in the PHEX gene in both patients but not among the 100 healthy controls. RT-PCR confirmed that exon 21 of the PHEX gene was deleted.</p><p><b>CONCLUSION</b>The novel splicing mutation IVS21+2T>G of the PHEX gene probably underlies the XLH in this pedigree. At the mRNA level, the mutation has led to removal of exon 21 and shift of the open reading frame (p.Val691fsx), resulting in premature termination of protein translation.</p>