The timely diagnosis of 49, XXXXY with the combined detection of MLPA, karyotype, and QF-PCR in a newborn with multiple congenital malformations: a case report.

Background: 49, XXXXY is a rare sex chromosomal aneuploidy syndrome. The patients usually are diagnosed several months or years after birth. Herein a neonate with respiratory distress and multiple malformations was diagnosed with 49, XXXXY syndrome by an economical method of multiplex ligation-dependent probe amplification (MLPA) followed karyotype analysis. Case Description: An infant was born via spontaneous vaginal delivery at 41+3 weeks' gestation and hospitalized due to neonatal asphyxia. He was the first child to a 24-year-old gravida1, para1 (G1P1) mother. The newborn was characterized low birth weight (2.4 Kg, below the 3rd percentile), and an Apgar score of 6 at 1 minute, 8 at 5 minutes, and 9 at 10 minutes. The physical examinations of the patient revealed ocular hypertelorism, epicanthal folds, low nasal bridge, high-arched palate, cleft palate, micrognathia, low-set ears, microcephaly, hypotonia, and micropenis. Echocardiography revealed atrial septal defects (ASD). The brainstem auditory evoked potential (BAEP) reflected auditory function impairment. Genetic testing methods, including MLPA, karyotyping, and quantitative fluorescent polymerase chain reaction (QF-PCR), were performed for definitive diagnosis, which confirmed 49, XXXXY syndrome. Conclusions: The presentation of the 49, XXXXY newborn was atypical, they may only include low birth weight, multiple malformations and a characteristic facial appearance which were consistent with the characteristics of autosomal and sex chromosome aneuploidies. At this time, the economical and rapid method of MLPA to screen the number of chromosome, and then choose the appropriate means to make the final diagnosis and improve the quality of life of patients with timely therapy.

[Genetic diagnosis of a case of Smith-Magenis syndrome due to a rare small-scale deletion].

OBJECTIVE: To report on a case of Smith-Magenis syndrome (SMS) due to a rare small-scale deletion. METHODS: Muscle samples from the the third fetus was collected after the in Medical history and clinical data of the patient were collected. The child and his parents were subjected to chromosome karyotyping analysis, multiplex ligation-dependent probe amplification (MLPA) and copy number variation sequencing (CNV-seq). RESULTS: The child was found to have a normal karyotype. MLPA and CNV-seq detection showed that he has harbored a 1.22 Mb deletion and a 0.3 Mb duplication in the 17p11.2 region. Neither of his parents was found to have similar deletion or duplication. CONCLUSION: The child was diagnosed with SMS due to a rare 1.22 Mb deletion in the 17p11.2 region, which is among the smallest deletions associated with this syndrome.

The pedigree analysis and prenatal diagnosis of Hong Kongαα Thalassemia and the sequence analysis of Hong Kongαα Allele.

BACKGROUND: Thalassemia is one of the most common monogenic hemolytic disorders in the world. Hong Kongαα (HKαα) thalassemia was initially found among the people of southern China. Because of the complexity of genetic changes in HKαα thalassemia, we lack a precise sequence analysis of the HKαα allele. Here we aim to detect the specific genotype and trace the law of inheritance of this rare genotype. METHODS: We recruited an unprecedented huge pedigree containing 11 individuals carrying the HKαα thalassemia gene and 4 nongenetic-related patients suffering from HKαα from south China. Regular hematological analysis and routine genetic screening were performed on the pedigree and two-round nested PCR (polymerase chain reaction) for HKαα thalassemia were performed on each individual. The first-generation gene sequencing was performed on six individuals, including four nongenetic-related patients. RESULT: We found that five family members were positive for the HKαα allele. Patients Ⅱ-2, Ⅲ-1, and Ⅱ-3 with only HKαα/--SEA or HKαα/-α4.2 presented with α-thalassemia minor trait. Ⅰ-1, the carrier of both HKαα/-α3.7 and ß41-42 /ßN , showed a typical ß-thalassemia trait. Fetus with genotype HKαα/-α4.2 alone was not likely to suffer from any deleterious effects after birth. The whole sequence of HKαα allele revealed that HKαα alleles in the six patients shared a high similarity, implying that all HKαα alleles are likely from the same ancestor. Moreover, pedigree and sequencing analyses demonstrated that the HKαα allele contained αααanti4.2 mutation, -α3.7 mutation, and a fragment from α-hemoglobin gene; thus, the composition and formation of HKαα allele was revealed. Finally, the high similarity and composition of HKαα alleles implies that once HKαα formed, αααanti4.2 and -α3.7 mutations tended to be a fusion gene and quite impossible to be inherited separately. CONCLUSION: The two-round nested PCR is an effective method to detect HKαα allele. Besides, our study for the first time revealed the sequence of the HKαα allele, the evidence of the same ancestor with HKαα thalassemia and enriched the composition as well as the formation mechanism of HKαα allele, and immediately opened up novel potential diagnosis and prenatal counseling for HKαα thalassemia.

The combination of 13N-ammonia and 18F-FDG PET/CT in the identification of metabolic phenotype of primary human brain tumors.

AIM: This pilot study made a preliminary attempt to distinguish different metabolic phenotypes of primary human brain tumors with dual tracer 13N-ammonia and 18F-FDG. METHODS: 74 patients were included in this study including 12 benign meningiomas (B-MEN), 4 malignant meningiomas (M-MEN), 15 low-grade gliomas (LGG), 32 high-grade gliomas (HGG) and 11 primary central nervous system lymphomas (PCNSL). All patients underwent 13N-ammonia and 18F-FDG PET imaging. Semi-quantification analysis by tumor-to-gray matter (T/G) ratios was used for the evaluation of tracer uptakes. After the calculation of canonical discriminant functions, cross validation was done for all cases to evaluate the differential efficacy of dual tracers. RESULTS: According to the visual analysis, B-MEN were characterized by lower uptake of 18F-FDG and higher uptake of 13N-ammonia, while PCNSLs displayed contrary results. Both M-MEN and HGG had higher uptake of 18F-FDG and 13N-ammonia, while LGG displayed negative results for both tracers. According to the T/G ratios analysis, the accuracy of predicted tumor classification by means of canonical discriminant analysis for B-MEN, LGG, HGG and PCNSL was 91.7 %, 100 %, 84.4 % and 93.3 % respectively; the overall accuracy was 90.5 %. CONCLUSION: The combination of dual tracer 13N-ammonia and 18F-FDG has a certain potential in distinguishing different types of brain tumors (meningiomas, gliomas and PCNSL). However, an advantage of the additional use of 13N-ammonia PET compared to a combined diagnosis with MRI and 18F-FDG PET could not be demonstrated and requires further studies.

The combination of 13N-ammonia and 18F-FDG whole-body PET/CT on the same day for diagnosis of advanced prostate cancer.

PURPOSE: The aim of the study was to evaluate the efficacy of 13N-ammonia and 18F-fluorodeoxyglucose (18F-FDG) PET performed on the same day in the detection of advanced prostate cancer (PC) and its metastases. PATIENTS AND METHODS: Twenty-six patients with high-risk PC [Gleason score 8-10 or prostate-specific antigen (PSA)> 20 ng/ml or clinical tumor extension ≥ T2c] were recruited into the study. 13N-Ammonia and 18F-FDG PET/CT were performed on the same day (18F-FDG followed ammonia, with an interval of a minimum of 2 h). Lesions were interpreted as positive, negative, or equivocal. Patient-based and field-based performance characteristics for both imaging techniques were reported. RESULTS: There was significant correlation between 13N-ammonia and 18F-FDG PET/CT in the detection of primary PC (κ=0.425, P=0.001) and no significant difference in sensitivity (60.2 vs. 54.5%) and specificity (100 vs. 83.3%). The maximum standard uptake values and corresponding target-to-background ratio values of the concordantly positive lesions in prostate glands in the two studies did not differ significantly (P=0.124 and 0.075, respectively). The sensitivity and specificity of PET imaging using 13N-ammonia for lymph node metastases were 77.5 and 96.3%, respectively, whereas the values were 75 and 44.4% using 18F-FDG. The two modalities were highly correlated with respect to the detection of lymph nodes and bone metastases. CONCLUSION: The concordance between the two imaging modalities suggests a clinical impact of 13N-ammonia PET/CT in advanced PC patients as well as of 18F-FDG. 13N-Ammonia is a useful PET tracer and a complement to 18F-FDG for detecting primary focus and distant metastases in PC. The combination of these two tracers on the same day can accurately detect advanced PC.

Biodistribution and estimation of radiation-absorbed doses in humans for 13N-ammonia PET.

OBJECTIVE: To evaluate the biodistribution of radiation-absorbed doses of (13)N-ammonia in healthy people. METHODS: Five healthy human subjects underwent whole-body PET and CT scans after injection of 555-740 MBq of (13)N-ammonia. Five serial dynamic emission scans in each healthy volunteer were acquired. Regions of interest were drawn on the CT image and transferred to the corresponding transverse PET slice. Estimates of the radiation-absorbed doses were calculated using the medical internal radiation dosimetry method. RESULTS: The highest concentrations of (13)N-ammonia were found in the heart and liver, followed by pancreas, brain, spleen and stomach. The highest absorbed organ doses were to the heart wall (7.14E-03 ± 3.63E-03 mGy/MBq) and kidneys (6.02E-03 ± 3.53E-03 mGy/MBq). The effective dose (ED) was 6.58E-03 ± 1.23E-03 mSv/MBq. CONCLUSIONS: With these new estimates for (13)N-ammonia dosimetry, the results for Chinese people were not appreciably different from those of the previous study performed with old devices. As one of the most important myocardial perfusion PET tracers, the whole-body (13)N-ammonia PET appears to be safe for humans, yielding a relatively modest radiation burden that would allow multiple PET studies on the same subject per year.

[Study of sharing platform of web-based enhanced extracorporeal counterpulsation hemodynamic waveform data].

Enhanced extracorporeal counterpulsation (EECP) information consists of both text and hemodynamic waveform data. At present EECP text information has been successfully managed through Web browser, while the management and sharing of hemodynamic waveform data through Internet has not been solved yet. In order to manage EECP information completely, based on the in-depth analysis of EECP hemodynamic waveform file of digital imaging and communications in medicine (DICOM) format and its disadvantages in Internet sharing, we proposed the use of the extensible markup language (XML), which is currently the Internet popular data exchange standard, as the storage specification for the sharing of EECP waveform data. Then we designed a web-based sharing system of EECP hemodynamic waveform data via ASP. NET 2.0 platform. Meanwhile, we specifically introduced the four main system function modules and their implement methods, including DICOM to XML conversion module, EECP waveform data management module, retrieval and display of EECP waveform module and the security mechanism of the system.

[The compression and storage of enhanced external counterpulsation waveform based on DICOM standard].

The development of external counterpulsation (ECP) local area network system and extensible markup language (XML)-based remote ECP medical information system conformable to digital imaging and communications in medicine (DICOM) standard has been improving the digital interchangeablity and sharability of ECP data. However, the therapy process of ECP is a continuous and longtime supervision which builds a mass of waveform data. In order to reduce the storage space and improve the transmission efficiency, the waveform data with the normative format of ECP data files have to be compressed. In this article, we introduced the compression arithmetic of template matching and improved quick fitting of linear approximation distance thresholding (LADT) in combimation with the characters of enhanced external counterpulsation (EECP) waveform signal. The DICOM standard is used as the storage and transmission standard to make our system compatible with hospital information system. According to the rules of transfer syntaxes, we defined private transfer syntax for one-dimensional compressed waveform data and stored EECP data into a DICOM file. Testing result indicates that the compressed and normative data can be correctly transmitted and displayed between EECP workstations in our EECP laboratory.

The semantic extension and storage of EECP Hemodynamic Waveforms based on DICOM Standard.

Digital imaging and communications in medicine (DICOM) Standard has a detailed description on the Information Object Definition (IOD) of all kinds of medical images and waveforms. With the development and application of DICOM, all medical imaging and waveform devices will support the standard. This article describes the method and implementation on how to encapsulate the EECP Hemodynamic Waveforms data acquired from EECP device, integrating patient information, EECP physiological parameters, and diagnosis and treat information into DICOM Hemodynamic Waveform file. We define Private Data Elements to encode and represent EECP parameters which haven't been registered as Standard Data Elements. This is the semantic extension of DICOM applied in EECP. The paper introduces following parts in detail: the structure of DICOM waveform file, Data Element, Nesting of Data Sets, the Waveform IOD Modules and the specification of Private Data Element. Then the method and process of our program are analyzed in depth. According to object-oriented methodology, firstly, Data Element, Nesting of Data Sets and waveform IOD with their corresponding operations and services are respectively abstracted into classes. Then the waveforms data and other attributes are assigned to the corresponding Data Members of the waveform class. Finally, they are stored into a DICOM waveform file by invoking related functions.