OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of a child with Acid-labile subunit deficiency (ALS). METHODS: A male child diagnosed with ALS at Dongguan Maternal and Child Health Care Hospital in March 2021 was selected as the study subject. Clinical data of his family was collected. Peripheral blood samples were collected from the child and his parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out, and Sanger sequencing was used for family verification of candidate variants. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of the candidate variant was classified. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2020-6). RESULTS: The patient, a 5-year-and-7-month-old boy, presented with short stature and delayed bone age. Endocrine examinations showed decreased serum concentrations of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP3). WES revealed that he has harbored compound heterozygous variants of the IGFALS gene, namely c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31. Sanger sequencing verified that the variants were inherited from his father and mother, respectively. According to the ACMG guidelines, c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31 variants were classified as likely pathogenic (PVS1+PM2_supporting). Based on the pre-set literature search strategy, 11 research literature on ALS were retrieved, which involved a total of 33 families and 62 patients. Combined with the patient in this study, 31 IGFALS gene variants were identified among the 63 patients, which mainly consisted of missense variants (20 types), with variant sites concentrated in exon 2. The main clinical features were short stature in conjunct with delayed puberty, with a significant genotype-phenotype correlation. CONCLUSION The IGFALS gene variants NM_004970.2: c.741_742del, p.Y248Pfs83 and c.272del, p.P91Rfs31 may be the genetic etiology in this family. This study has expanded the variant spectrum of the IGFALS gene and provided valuable information for the diagnosis, genetic counseling and clinical treatment of the disease.
Humans ; Male ; Phenotype ; Child, Preschool ; Carrier Proteins/genetics* ; Glycoproteins/deficiency* ; Exome Sequencing ; Female ; Mutation ; Insulin-Like Growth Factor I/metabolism* ; Growth Disorders/genetics*

Objective To evaluate the predictive factors for failure of non-invasive positive pressure ventilation (NIPPV) in immunosuppressed patients with acute respiratory failure (ARF). Methods The clinical data of 118 immuno-deficient patients treated with NIPPV in the respiratory and intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from January 2012 to August 2017 were retrospectively analyzed. The patients were divided into a non-endotracheal intubation (ETI) group (n = 62) and ETI group (n = 56) according to whether ETI was performed during the hospitalization period or not. Each observed indicator was analyzed by univariate analysis, and factors leading to failure of NIPPV were further analyzed by Logistic regression. Receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of risk factors for failure of NIPPV in immunosuppressed patients with ARF. Results The non-intubation rate for NIPPV in immunosuppressed patients was 50.8% (60/118). Compared with the non-ETI group, the body temperature, pH value in the ETI group were significantly increased, the partial pressure of arterial carbon dioxide (PaCO2) was significantly decreased, the ratio of oxygenation index (PaO2/FiO2) < 100 mmHg (1 mmHg = 0.133 kPa), acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) score ≥ 20, and the number of cases requiring catecholamine were significantly increased, the mortality was significantly increased. Multivariate Logistic regression analysis showed that the APACHE Ⅱ score ≥ 20 [odds ratio (OR) = 15.274, 95% confidence internal (95%CI) = 2.175-107.252, χ2= 7.516, 1 = 0.006], PaO2/FiO2< 100 mmHg (OR = 0.075, 95%CI = 0.014-0.408, χ2= 8.968, 1 = 0.003), and need for catecholamine (OR = 35.736, 95%CI = 6.974-183.124, χ2= 18.400, 1 < 0.001) were independent risk factors for failure of NIPPV. ROC curve analysis showed that the APACHE Ⅱ score ≥ 20 and PaO2/FiO2< 100 mmHg could predict failure of NIPPV, the area under ROC curve (AUC) of the APACHE Ⅱ score ≥ 20 was 0.787, the sensitivity was 83.93%, the specificity was 69.35%, the positive predict value (PPV) was 71.21%, the negative predict value (NPV) was 82.69%, the positive likelihood ratio (PLR) was 2.74, the negative likelihood ratio (NLR) was 0.23, and Youden index was 0.53; the AUC of PaO2/FiO2< 100 mmHg was 0.757, the sensitivity was 80.65%, the specificity was 66.07%, the PPV was 68.18%, the NPV was 78.85%, the PLR was 2.38, the NLR was 0.29, and Youden index was 0.47. Conclusions 50.8% of immunocompromised and ARF patients treated with NIPPV did not require ETI, which is independent of the etiology of ARF. APACHE Ⅱ score ≥ 20, PaO2/FiO2<100 mmHg, and the need for catecholamine are predictive factors for failure of NIPPV in immunocompromised patients.

Objective The NDRG4 gene methylation in stool is a candidate biomarker for non?invasive diagnosis of colorectal cancer. However, the traditional methods for methylation detection could not be well applied to stool samples due to the low sensitivity and low specificity. The aim of this study was to develop a highly sensitive and specific method for quantifying the methylated NDRG4 gene in stools. Methods Forty one stool samples were collected from 12 colorectal cancer patients, 4 adenoma patients and 25 nor?mal persons. The invasive reaction was combined with real?time PCR and the relative quantification was performed by 2-ΔCT method to develop the highly sensitive and specific methylated DNA detection method, which was used for detecting NDRG4 methylation levels in 41 of stool samples. Results The sensitivity of the method was as low as 10 copies of methylated NDRG4 gene fragments. The specificity was high enough to distinguish 0.01% of methylated fragments from un?methylated fragments and 105 copies of unmethylated NDRG4 fragments gave noamplification signals. The detection results from 41 of stool samples showed that detection rate of the NDRG4 gene in stool from adenoma and colorectal cancer groups had a significant difference comparing to that from the normal group. Conclusion The 2-ΔCT method could accurately quantify the methylation levels of the NDRG4 gene in stool samples, and provide an efficient tool for non?invasive colorectal cancer detection.