Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 119
Filter
1.
Article in English | WPRIM | ID: wpr-874174

ABSTRACT

Background@#Hepatocellular carcinoma (HCC) is the second-most-common cause of cancer-related deaths worldwide, and an accurate and non-invasive biomarker for the early detection and monitoring of HCC is required. We assessed pathogenic variants of HCC driver genes in cell-free DNA (cfDNA) from HCC patients who had not undergone systemic therapy. @*Methods@#Plasma cfDNA was collected from 20 HCC patients, and deep sequencing was performed using a customized cfDNA next-generation sequencing panel, targeting the major HCC driver genes (TP53, CTNNB1, TERT) that incorporates molecular barcoding. @*Results@#In 13/20 (65%) patients, we identified at least one pathogenic variant of two major HCC driver genes (TP53 and CTNNB1), including 16 variants of TP53 and nine variants of CTNNB1. The TP53 and CTNNB1 variants showed low allele frequencies, with median values of 0.17% (range: 0.06%–6.99%) and 0.07% (range: 0.05%–0.96%), respectively. However, the molecular coverage of variants was sufficient, with median values of 5,543 (range: 2,317–9,088) and 7,568 (range: 2,400–9,633) for TP53 and CTNNB1 variants, respectively. @*Conclusions@#Our targeted DNA sequencing successfully identified low-frequency pathogenic variants in the cfDNA from HCC patients by achieving high coverage of unique molecular families. Our results support the utility of cfDNA analysis to identify somatic gene variants in HCC patients.

2.
Blood Research ; : 159-168, 2020.
Article | WPRIM | ID: wpr-831005

ABSTRACT

Background@#Plasma cell myeloma (PCM) is a genetically heterogeneous disease. The genetic spectrum of PCM has been expanded to mutations such as KRAS, NRAS, and BRAF genes in the RAS-RAF-MAPK pathway. In this study, we have evaluated the frequency of these mutations and their significance, including baseline characteristics and clinical outcomes. @*Methods@#We explored 50 patients who were newly diagnosed with PCM between 2009 and 2012 at a single Korean institute. Clinical and laboratory parameters were gathered through careful review of medical records. Mutation analysis was carried out using DNA from the bone marrow at the time of diagnosis. Pyrosequencing was performed to detect KRAS G12V,KRASG13D, and NRAS G61R. BRAF V600E was analyzed by allele-specific real-time PCR. Comparison of clinical and laboratory parameters was carried out according to those mutations. @*Results@#We identified 14 patients (28%) with activating mutations in the RAS-RAF-MAPK pathway (RAS/RAF mutations):KRAS (N=3), KRAS (N=4),BRAF (N=7), and both KRAS and BRAF (N=1). RAS/RAF mutations were more frequently observed in patients with complex karyotypes and showed poorer progression free survival (PFS). Specifically, the BRAF V600E mutation had a significantly negative impact on median PFS. @*Conclusion@#We first showed the frequency of RAS/RAF mutations in Korean patients with PCM.Screening of these mutations could be considered as a routine clinical test at the time of diagnosis and follow-up due to their influence on clinical outcome, as well as its potential as a therapeutic target.

3.
Blood Research ; : 17-26, 2020.
Article in English | WPRIM | ID: wpr-820807

ABSTRACT

BACKGROUND: DNMT3A mutations occur in approximately 20% of AML cases and are associated with changes in DNA methylation. CDKN2B plays an important role in the regulation of hematopoietic progenitor cells and DNMT3A mutation is associated with CDKN2B promoter methylation. We analyzed the characteristics of DNMT3A mutations including their clinical significance in AML and their influence on promoter methylation and CDKN2B expression.METHODS: A total of 142 adults, recently diagnosed with de novo AML, were enrolled in the study. Mutations in DNMT3A, CEBPA, and NPM1 were analyzed by bidirectional Sanger sequencing. We evaluated CDKN2B promoter methylation and expression using pyrosequencing and RT-qPCR.RESULTS: We identified DNMT3A mutations in 19.7% (N=28) of enrolled patients with AML, which increased to 29.5% when analysis was restricted to cytogenetically normal-AML. Mutations were located on exons from 8–23, and the majority, including R882, were found to be present on exon 23. We also identified a novel frameshift mutation, c.1590delC, in AML with biallelic mutation of CEBPA. There was no significant difference in CDKN2B promoter methylation according to the presence or type of DNMT3A mutations. CDKN2B expression inversely correlated with CDKN2B promoter methylation and was significantly higher in AML with R882H mutation in DNMT3A. We demonstrated that DNMT3A mutation was associated with poor AML outcomes, especially in cytogenetically normal-AML. The DNMT3A mutation remained as the independent unfavorable prognostic factor after multivariate analysis.CONCLUSION: We characterized DNMT3A mutations in AML and revealed the association between the DNMT3A mutation and CDKN2B expression and clinical outcome.


Subject(s)
Adult , DNA Methylation , Exons , Frameshift Mutation , Hematopoietic Stem Cells , Humans , Leukemia, Myeloid, Acute , Methylation , Multivariate Analysis
4.
Article in English | WPRIM | ID: wpr-762472

ABSTRACT

BACKGROUND: Hereditary breast and ovarian cancer syndrome (HBOC) is caused by pathogenic variants in BRCA and other cancer-related genes. We analyzed variants in BRCA gene and other cancer-related genes in HBOC patients to evaluate the clinical validity of next-generation sequencing (NGS) multi-gene panel testing. METHODS: The BRCA1/2 NGS testing was conducted for 262 HBOC patients. Multiplex ligation-dependent probe amplification and direct Sanger sequencing were performed for confirmation. Multi-gene panel testing was conducted for 120 patients who did not possess BRCA1/2 pathogenic variants but met the National Comprehensive Cancer Network criteria. RESULTS: Pathogenic variants in BRCA1/2 were detected in 30 HBOC patients (11.5%). Additionally, four out of the 120 patients possessed pathogenic variants by multi-gene panel testing (3.3%): MSH2 (c.256G>T, p.Glu86*), PMS2 (c.1687C>T, p.Arg563*), CHEK2 (c.546C>A, p.Tyr182*), and PALB2 (c.3351-1G>C). All the four patients had a family history of cancer. CONCLUSIONS: Multi-gene panel testing could be a significant screening tool for HBOC patients, especially for those with a family history of cancer.


Subject(s)
Hereditary Breast and Ovarian Cancer Syndrome , Humans , Mass Screening , Multiplex Polymerase Chain Reaction
5.
Article in English | WPRIM | ID: wpr-762452

ABSTRACT

Evaluation of diagnostic tests requires reference standards, which are often unavailable. Latent class analysis (LCA) can be used to evaluate diagnostic tests without reference standards, using a combination of observed and estimated results. Conditionally independent diagnostic tests for Helicobacter pylori infection are required. We used LCA to construct a reference standard and evaluate the capability of non-invasive tests (stool antigen test and serum antibody test) to diagnose H. pylori infection compared with the conventional method, where histology is the reference standard. A total of 96 healthy subjects with endoscopy histology results were enrolled from January to July 2016. Sensitivity and specificity were determined for the LCA approach (i.e., using a combination of three tests as the reference standard) and the conventional method. When LCA was used, sensitivity and specificity were 83.8% and 99.4% for histology, 80.0% and 81.9% for the stool antigen test, and 63.6% and 89.3% for the serum antibody test, respectively. When the conventional method was used, sensitivity and specificity were 75.8% and 71.1% for the stool antigen test and 77.7% and 60.7% for the serum antibody test, respectively. LCA can be applied to evaluate diagnostic tests that lack a reference standard.


Subject(s)
Diagnosis , Diagnostic Tests, Routine , Endoscopy , Healthy Volunteers , Helicobacter pylori , Helicobacter , Methods , Sensitivity and Specificity
6.
Blood Research ; : 52-56, 2019.
Article in English | WPRIM | ID: wpr-739434

ABSTRACT

BACKGROUND: Granulocyte transfusion (GTx) is performed as a supportive therapy in severe neutropenic patients caused by various conditions. The study aimed to analyze the hematologic parameters of donors, patients, and granulocyte concentrates to predict successful GTx. METHODS: This study was performed in 281 donors, with their granulocyte concentrates being collected through apheresis, and in 54 severe neutropenic patients who had various hematologic diseases. Complete blood cell counts of donors pre- and post-apheresis, granulocyte concentrates, and patients pre- and post-GTx were analyzed. Patients were divided into two groups according to survival at discharge (Group S, survival; Group D, dead) to compare various factors including age, infection status, pre- and post-GTx total white blood cell counts (TWBCC) and absolute neutrophil counts (ANC), total number of GTx, infused TWBCC and ANC per weight, and use of G-CSF during therapy. RESULTS: Overall data of patients showed that both TWBCC and ANC were significantly increased after GTx (median values at pre-GTx, TWBCC=0.40×109/L, ANC=0.14×109/L; post-GTx, TWBCC=0.57×109/L, ANC=0.29×109/L, both P<0.0001). After GTx, Group S (N=25) showed significantly higher TWBCC and ANC than Group D (N=29) (P=0.01 and P=0.04, respectively). Using different cutoff levels, post-GTx TWBCC greater than 0.5×109/L showed statistically significant difference between the two groups (P<0.01). None of the other factors showed statistically significant differences. CONCLUSION: The TWBCC and ANC after GTx were significant factors to predict patients' outcome. Therefore, follow-up of those two parameters may be helpful to select or consider other therapeutic modalities including additional GTx.


Subject(s)
Blood Cell Count , Blood Component Removal , Follow-Up Studies , Granulocyte Colony-Stimulating Factor , Granulocytes , Hematologic Diseases , Humans , Leukocyte Count , Neutropenia , Neutrophils , Tissue Donors
7.
Article in English | WPRIM | ID: wpr-739133

ABSTRACT

BACKGROUND: It is very important to accurately enumerate CD34-positive (CD34+) cells for successful hematopoietic stem cell transplantation (HSCT). We evaluated the ability of the newly developed image based-immunofluorescence cell counter ADAMII (NanoEntek, Seoul, Korea) to enumerate CD34+ cells, which was improved through simultaneous CD45 analysis. METHODS: We enumerated CD34+ cells with ADAMII using 19 peripheral blood (PB) and 91 leukapheresis samples from HSCT donors. Analytical performance, including precision and linearity, was analyzed, and sample stability during storage was evaluated. Viable CD34+ cell count (vCD34) and viable CD45+ cell count (vCD45) and the percentage of viable CD34+ cells among viable CD45+ cells (CD34/CD45) as measured by ADAMII were compared with the corresponding values from two flow cytometry assays, using regression analysis. RESULTS: ADAMII demonstrated acceptable precision, as CV values of vCD34 from six samples with different counts were all < 10% (range: 3.49–9.51%). CV values of the vCD45 and CD34/45 ranged from 4.03% to 9.67% and from 2.48% to 10.07%, respectively. The linearity of vCD34 showed an excellent R 2 value (0.99) when analyzed using the intended count and flow cytometry data. The ADAMII and two flow cytometry-based assays generated very similar data for the PB and leukapheresis samples. CONCLUSIONS: ADAMII demonstrated excellent performance for use as a routine clinical assay in terms of CD34+ cell enumeration from PB and leukapheresis samples. Moreover, it could be used as a point-of-care-test for determining mobilization time and predicting an adequate apheresis stem cell product.


Subject(s)
Blood Component Removal , Cell Count , Flow Cytometry , Fluorescence , Hematopoietic Stem Cell Transplantation , Humans , Leukapheresis , Seoul , Stem Cells , Tissue Donors
8.
Article in English | WPRIM | ID: wpr-739122

ABSTRACT

BACKGROUND: To validate the clinical application of chromosomal microarray analysis (CMA) as a first-tier clinical diagnostic test and to determine the impact of CMA results on patient clinical management, we conducted a multicenter prospective study in Korean patients diagnosed as having developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and multiple congenital anomalies (MCA). METHODS: We performed both CMA and G-banding cytogenetics as the first-tier tests in 617 patients. To determine whether the CMA results directly influenced treatment recommendations, the referring clinicians were asked to complete a 39-item questionnaire for each patient separately after receiving the CMA results. RESULTS: A total of 122 patients (19.8%) had abnormal CMA results, with either pathogenic variants (N=65) or variants of possible significance (VPS, N=57). Thirty-five well-known diseases were detected: 16p11.2 microdeletion syndrome was the most common, followed by Prader-Willi syndrome, 15q11-q13 duplication, Down syndrome, and Duchenne muscular dystrophy. Variants of unknown significance (VUS) were discovered in 51 patients (8.3%). VUS of genes putatively associated with developmental disorders were found in five patients: IMMP2L deletion, PTCH1 duplication, and ATRNL1 deletion. CMA results influenced clinical management, such as imaging studies, specialist referral, and laboratory testing in 71.4% of patients overall, and in 86.0%, 83.3%, 75.0%, and 67.3% of patients with VPS, pathogenic variants, VUS, and benign variants, respectively. CONCLUSIONS: Clinical application of CMA as a first-tier test improves diagnostic yields and the quality of clinical management in patients with DD/ID, ASD, and MCA.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Cytogenetics , Diagnostic Tests, Routine , Down Syndrome , Humans , Intellectual Disability , Korea , Microarray Analysis , Muscular Dystrophy, Duchenne , Prader-Willi Syndrome , Prospective Studies , Referral and Consultation , Specialization
9.
Article in English | WPRIM | ID: wpr-739121

ABSTRACT

We reviewed our leukemia database to reclassify 610 patients previously diagnosed as having acute myeloid leukemia (AML) according to the updated 2016 WHO classification. Nine patients were categorized as having myelodysplastic syndrome and myeloid neoplasms with germline predisposition. AML with recurrent genetic abnormalities accounted for 57.4% (345/601) of the patients under the 2016 WHO classification. AML with mutated NPM1 was the most common form (16.5%), with the majority associated with monocytic differentiation (63.6%). AML with double CEBPA mutations accounted for 8.3% of these cases, and the majority were previously diagnosed as AML with/without maturation (78.0%). These newly classified mutations were mutually exclusive without overlapping with other forms of AML with recurrent genetic abnormalities. AML with mutated NPM1 and AML with myelodysplasia-related changes comprised the oldest patients, whereas AML with RUNX1-RUNX1T1 included the youngest patients. The leukocyte count was highest in AML with mutated NPM1, and the percentage of peripheral blood blasts was the highest in AML with double CEBPA mutations. Our results indicate that implementation of the 2016 WHO classification of AML would not pose major difficulties in clinical practice. Hematopathologists should review and prepare genetic tests for the new classification, according to their clinical laboratory conditions.


Subject(s)
Classification , Humans , Leukemia , Leukemia, Myeloid, Acute , Leukocyte Count , Myelodysplastic Syndromes
10.
Article in English | WPRIM | ID: wpr-719474

ABSTRACT

The detection and quantification of hepatitis B virus (HBV) DNA plays an important role in diagnosing and monitoring HBV infection as well as in assessing the therapeutic response. We compared the analytical performance of a random access, fully automated HBV assay—DxN VERIS Molecular Diagnostics System (Beckman Coulter, Brea, CA, USA)—with that of Abbott RealTime HBV assay (Abbott Laboratories, Des Plaines, IL, USA). The between-day precision of the VERIS assay ranged from 0.92% (mean 4.68 log IU/mL) to 4.15% (mean 2.09 log IU/mL) for pooled sera from HBV patients. HBV DNA levels measured by the VERIS HBV assay correlated with the calculated HBV DNA levels (r²=0.9994; P < 0.0001). The lower limit of quantification was estimated as 8.76 IU/mL (Probit analysis, 95% confidence interval: 7.32–12.00 IU/mL). Passing-Bablok regression analysis showed good concordance between the VERIS and RealTime assays for 187 chronic HBV samples (y=−0.2397+0.9712x; r=0.981), as well as for 20 drug-resistant HBV genotype C positive samples (y=−0.5415+0.9954x; r=0.961). The VERIS assay demonstrated performance similar to the RealTime assay and is suitable for high-throughput HBV DNA monitoring in large hospital laboratories.


Subject(s)
DNA , Genotype , Hepatitis B virus , Hepatitis B , Hepatitis , Humans , Laboratories, Hospital , Pathology, Molecular
12.
Laboratory Medicine Online ; : 114-118, 2018.
Article in Korean | WPRIM | ID: wpr-715908

ABSTRACT

Hereditary spherocytosis (HS) is caused by mutations in the SPTA1, SPTB, ANK1, SLC4A1, and EPB42 genes, all of which encode erythrocyte membrane proteins. Mutations in SLC4A1, which encodes band 3 protein, have rarely been reported as the causative factor among Korean patients with HS. Here, we report two Korean patients with HS carrying mutations in SLC4A1. Patient 1 was a 3-year-old girl with unremarkable past and family histories and was evaluated for anemia that was detected after a complete blood count. She was suspected of having HS considering the spherocytosis of her peripheral blood smear, increased osmotic fragility, hemolytic features in blood chemistry tests, and splenomegaly. Sequence analysis revealed that the patient harbored a single heterozygous missense mutation, c.2278C>T (p.Arg760Trp) in exon 17 of SLC4A1. Patient 2 was a 23-year-old man who had a prior history of intermittent jaundice. Although the patient did not have anemia, a genetic test for HS was performed due to evidence of hemolytic features in the blood chemistry test, splenomegaly, and a family history of HS. The test confirmed a single heterozygous missense mutation, c.2423G>T (p.Arg808Leu) in exon 18 of SLC4A1.


Subject(s)
Anemia , Anion Exchange Protein 1, Erythrocyte , Blood Cell Count , Chemistry , Child, Preschool , Erythrocyte Membrane , Exons , Female , Humans , Jaundice , Mutation, Missense , Osmotic Fragility , Sequence Analysis , Splenomegaly , Young Adult
15.
Article in English | WPRIM | ID: wpr-718324

ABSTRACT

BACKGROUND: Accurate, rapid, and cost-effective screening tests for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection may be useful in laboratories that cannot afford automated chemiluminescent immunoassays (CLIAs). We evaluated the diagnostic performance of a novel rapid automated fluorescent lateral flow immunoassay (LFIA). METHODS: A fluorescent LFIA using a small bench-top fluorescence reader, Automated Fluorescent Immunoassay System (AFIAS; Boditech Med Inc., Chuncheon, Korea), was developed for qualitative detection of hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), and antibody to HCV (anti-HCV) within 20 minutes. We compared the diagnostic performance of AFIAS with that of automated CLIAs—Elecsys (Roche Diagnostics GmbH, Penzberg, Germany) and ARCHITECT (Abbott Laboratories, Abbott Park, IL, USA)—using 20 seroconversion panels and 3,500 clinical serum samples. RESULTS: Evaluation with the seroconversion panels demonstrated that AFIAS had adequate sensitivity for HBsAg and anti-HCV detection. From the clinical samples, AFIAS sensitivity and specificity were 99.8% and 99.3% for the HBsAg test, 100.0% and 100.0% for the anti-HBs test, and 98.8% and 99.1% for the anti-HCV test, respectively. Its agreement rates with the Elecsys HBsAg, anti-HBs, and anti-HCV detection assays were 99.4%, 100.0%, and 99.0%, respectively. AFIAS detected all samples with HBsAg genotypes A-F and H and anti-HCV genotypes 1, 1a, 1b, 2a, 2b, 4, and 6. Cross-reactivity with other infections was not observed. CONCLUSIONS: The AFIAS HBsAg, anti-HBs, and anti-HCV tests demonstrated diagnostic performance equivalent to current automated CLIAs. AFIAS could be used for a large-scale HBV or HCV screening in low-resource laboratories or low-to middle-income areas.


Subject(s)
Fluorescence , Genotype , Hepacivirus , Hepatitis B Surface Antigens , Hepatitis B virus , Hepatitis B , Hepatitis C , Hepatitis , Immunoassay , Mass Screening , Sensitivity and Specificity , Seroconversion
16.
Article in English | WPRIM | ID: wpr-715639

ABSTRACT

BACKGROUND: Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA-M2BP) is a protein with altered glycosylation that reacts with lectin, and was recently identified as a useful non-invasive biomarker for the diagnosis of liver fibrosis in patients with hepatitis C virus infection.This study aimed to evaluate the diagnostic efficacy of WFA-M2BP for liver fibrosis in the context of hepatitis B virus (HBV). METHODS: We enrolled 151 patients infected with HBV. Liver biopsy and elastography (Fibroscan) were performed during the initial visit. Fibrosis was graded according to the Knodell histologic activity index (F0–3). WFA-M2BP levels were determined with an automated immunoassay analyzer (M2BPGi, HISCL-5000, Sysmex, Japan). The diagnostic efficacy of WFA-M2BP was compared with those of various conventional or composite biomarkers, including enhanced liver fibrosis (ELF) score, Fibroscan, aspartate transaminase (AST)-to-platelet ratio index (APRI), and FIB-4, based on the area under the ROC curve (AUC) value. RESULTS: The majority of patients were at fibrosis stages F1 and F2. The F2 and F3 AUC values for WFA-M2BP were similar to those for FIB-4, APRI, ELF, and Fibroscan, although the latter showed the best diagnostic efficacy. The diagnostic accuracy of all tested biomarkers for F2 and F3 was 60–70%. In multivariate analysis, WFA-M2BP, ELF, and platelet count significantly predicted stage ≥F2, whereas only platelet count significantly predicted F3. CONCLUSIONS: WFA-M2BP can support a diagnosis of liver fibrosis with similar diagnostic efficacy to other biomarkers, and predicted liver fibrosis stage ≥2 among patients with chronic hepatitis B.


Subject(s)
Area Under Curve , Aspartate Aminotransferases , Biomarkers , Biopsy , Carrier Proteins , Diagnosis , Elasticity Imaging Techniques , Fibrosis , Glycosylation , Hepacivirus , Hepatitis B , Hepatitis B virus , Hepatitis B, Chronic , Hepatitis, Chronic , Humans , Immunoassay , Liver Cirrhosis , Liver , Multivariate Analysis , Platelet Count , ROC Curve , Wisteria
17.
Article in English | WPRIM | ID: wpr-715638

ABSTRACT

BACKGROUND: Carcinoembryonic antigen (CEA) is one of the tumor markers available for evaluating disease progression status after initial therapy and monitoring subsequent treatment modalities in colorectal, gastrointestinal, lung, and breast carcinoma. We evaluated the correlations and differences between widely used, automated CEA immunoassays at four different medical laboratories. METHODS: In total, 393 serum samples with CEA ranging from 3.0 to 1,000 ng/mL were analyzed on ADVIA Centaur XP (Siemens Diagnostics, Tarrytown, NY, USA), ARCHITECT i2000sr (Abbott Diagnostics, Abbott Park, IL, USA), Elecsys E170 (Roche Diagnostics, Indianapolis, IN, USA), and Unicel DxI800 (Beckman Coulter, Fullerton, CA, USA), and the results were compared. Deming regression, Passing-Bablok regression, and Bland-Altman analyses were performed to evaluate the data correlation and % differences among these assays. RESULTS: Deming regression analysis of data from Elecsys E170 and UniCel DxI800 showed good correlation (y=3.1615+0.8970x). According to Bland-Altman plot, no statistically significant bias (−1.78 ng/mL [95% confidence interval: −4.02 to 0.46]) was observed between Elecsys E170 and UniCel DxI800. However, the relative differences of CEA concentrations between assays exceeded the acceptable limit of 30%. Regarding the agreement of positivity with cut-off value 5.0 ng/mL, ARCHITECT i2000sr and Elecsys E170 showed the highest agreement (95.2%), whereas ADVIA Centaur XP and ARCHITECT i2000sr showed the lowest agreement (70.7%). CONCLUSIONS: Agreements between automated CEA immunoassays are variable, and individual CEA concentrations may differ significantly between assays. Standardization of serum CEA concentrations and further harmonization are needed.


Subject(s)
Bias , Biomarkers, Tumor , Breast Neoplasms , Carcinoembryonic Antigen , Disease Progression , Immunoassay , Lung , Statistics as Topic
18.
Article in English | WPRIM | ID: wpr-129953

ABSTRACT

No abstract available.


Subject(s)
Humans , Kansas
19.
Article in English | WPRIM | ID: wpr-129939

ABSTRACT

No abstract available.


Subject(s)
Humans , Kansas
20.
Article in English | WPRIM | ID: wpr-169860

ABSTRACT

Pseudohypoparathyroidism (PHP) is a rare disorder caused by genetic and epigenetic aberrations in the GNAS complex locus resulting in impaired expression of stimulatory G protein (Gsα). PHP type Ib (PHP-Ib) is characterized by hypocalcemia and hyperphosphatemia due to renal resistance to the parathyroid hormone, and is distinguished from PHP-Ia by the absence of osteodystrophic features. An 11-yr-old boy presented with poor oral intake and cramping lower limb pain after physical activity. Laboratory studies revealed hypocalcemia, hyperphosphatemia, and increased parathyroid hormone levels. The GNAS complex locus was evaluated using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Gain of methylation in the NESP55 domain and loss of methylation in the antisense (AS) transcript, XL, and A/B domains in the maternal allele were observed. Consequently, we present a case of PHP-Ib diagnosed using MS-MLPA.


Subject(s)
Alleles , Epigenomics , GTP-Binding Proteins , Humans , Hyperphosphatemia , Hypocalcemia , Lower Extremity , Male , Methylation , Motor Activity , Multiplex Polymerase Chain Reaction , Muscle Cramp , Parathyroid Hormone , Pseudohypoparathyroidism
SELECTION OF CITATIONS
SEARCH DETAIL