OBJECTIVE: To analyze the incidence of abnormal hemoglobin (Hb) in neonates in Guangzhou area, as well as the results of quantitative analysis of Hb in neonatal umbilical cord blood and genetic diagnosis of thalassemia in neonates with abnormal Hb; And to explore the hematological phenotypes and clinical characteristics of neonates with abnormal Hb and their parents, providing a reference for eugenics and childcare. METHODS: 650 neonates born at Guangdong Provincial People's Hospital who underwent Hb electrophoresis were included in this study. The results of routine blood test of umbilical cord blood , Hb electrophoresis and α-, β-thalassemia gene detection of the neonates were collected. The genotype distribution of thalassemia in the neonates was analyzed. Additionally, the abnormal Hb content of α and β variants was studied. Furthermore, the differences in hematological parameters between abnormal Hb neonates and normal neonates and α-thalassemia neonates, as well as between the parents of abnormal Hb neonates and normal adults were compared. RESULTS: Among the 650 neonates, 332 (51.08%) were diagnosed with thalassemia, including 235 cases of α-thalassemia (36.15%), 79 cases of β-thalassemia (12.15%), and 18 cases of compound αβ-thalassemia (2.77%). Among all the α-thalassemia genotypes, the most prevalent one was -- ^SEA/αα (48.94%), followed by -α^3.7/αα (20.00%), -α^4.2/αα (11.06%), and αα^CS/αα (8.94%). The four most common genotypes of β-thalassemia were β^CD41-42 (32.91%), β^IVS-Ⅱ-654 (26.58%), β^-28 (21.52%), and β^E (10.13%), respectively. 275 cases of abnormal bands were found in Hb electrophoresis of umbilical cord blood, with a detection rate of 42.31%. The abnormal Hb content of α-variant in the neonates was significantly higher than that of β-variant (P < 0.001). The levels of Hb, MCV, MCH, Hb A, and Hb F in neonates with abnormal Hb were lower than those in normal neonates, while the RDW-CV was higher than that in normal neonates, with statistical significantce (P < 0.05). The levels of RBC and Hb A in neonates with abnormal Hb were lower than those in neonates with α-thalassemia, while the level of MCH was higher than that in neonats with α-thalassemia, with statistical significance (P < 0.05). The levels of Hb, MCV, MCH, and Hb A in parents of neonates with abnormal Hb were lower than those in normal adults, while the RDW-CV was higher than that in normal adults, and the differences were statistically significant (P < 0.05). CONCLUSION The abnormal Hb content of α-variant in the neonates is significantly higher than that of β-variant in the neonates in Guangzhou, which can help to presume whether it is α chain or β chain based on the abnormal Hb content, providing a reference for globin gene sequencing. Meanwhile, analysis of various hematological screening-related indicators in neonates in the early stage is beneficial for early warning of the occurrence of abnormal Hb combined with thalassemia, reducing missed diagnoses to a certain extent.
Humans ; Infant, Newborn ; Genotype ; Hemoglobins, Abnormal/genetics* ; China/epidemiology* ; alpha-Thalassemia/epidemiology* ; beta-Thalassemia/genetics* ; Parents ; Female ; Male ; Fetal Blood

CAPOS syndrome is an autosomal dominant neurological disorder caused by mutations in the ATP1A3 gene. Initial symptoms, often fever-induced, include recurrent acute ataxic encephalopathy in childhood, featuring cerebellar ataxia, optic atrophy, areflflexia, sensorineural hearing loss, and in some cases, pes cavus. This report details a case of CAPOS syndrome resulting from a maternal ATP1A3 gene mutation. Both the child and her mother exhibited symptoms post-febrile induction,including severe sensorineural hearing loss in both ears, ataxia, areflexia, and decreased vision. Additionally, the patient's mother presented with pes cavus. Genetic testing revealed a c. 2452G>A（Glu818Lys） heterozygous mutation in theATP1A3 gene in the patient . This article aims to enhance clinicians' understanding of CAPOS syndrome, emphasizing the case's clinical characteristics, diagnostic process, treatment, and its correlation with genotypeic findings.
Humans ; Child ; Female ; Cerebellar Ataxia/diagnosis* ; Talipes Cavus ; Hearing Loss, Sensorineural/diagnosis* ; Optic Atrophy/diagnosis* ; Mutation ; Phenotype ; Sodium-Potassium-Exchanging ATPase/genetics* ; Foot Deformities, Congenital ; Reflex, Abnormal

Humans ; Hemoglobinopathies ; Hemoglobins, Abnormal/genetics*

Humans ; Hematopoietic Stem Cell Transplantation ; Hemoglobinopathies/therapy* ; Hemoglobins, Abnormal

OBJECTIVE: To explore the genetic basis for a child with Hemoglobin Santa Ana (Hb Santa Ana). METHODS: The child was admitted to the Children's Hospital of Chongqing Medical University on August 4, 2013 due to anemia, splenomegaly and deepening urine color for 5 years. His clinical data were collected. Peripheral blood samples of the child and his parents were collected for routine blood test. The erythrocyte parameters of the child and his parents were determined with an automatic hemocyte analyzer. The hemoglobin components of the child and his parents were detected by high-performance liquid chromatography (HPLC). Common mutations associated with thalassemia were detected by Gap-PCR and PCR-reverse dot blotting (PCR-RDB). Rare variants of the globin genes were detected by next generation sequencing (NGS), and the result was verified by Sanger sequencing. RESULTS: The child has shown mild to moderate hemolytic anemia. Routine blood test showed that he had lower hemoglobin (90 g/L) and mean corpuscular hemoglobin concentration (267 g/L) but a higher reticulocyte ratio (0.141), which indicated hypopigmented hyperplastic anemia. Analysis of hemoglobin component showed that his hemoglobin F was elevated to 10.7%, which indicated abnormal synthesis of β globin peptide chain. HPLC analysis showed an abnormal peak accounting for 4.5% of the total area. Neither of his parents was found to have abnormal results for routine blood test and hemoglobin component analysis. No common globin gene variant was detected in the child. Gene sequencing revealed that the child has harbored a heterozygous variant of HBB: c.266T>C, which was de novo in origin. Based on the guidelines of American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic. CONCLUSION The heterozygous HBB: c.266T>C variant probably underlay the hemolytic anemia associated with Hb Santa Ana in this patient.
Child ; Humans ; Male ; Chromatography, High Pressure Liquid ; Hemoglobins, Abnormal/genetics*

OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with intellectual disability (ID), developmental delay (DD), and autistic spectrum disorder (ASD). METHODS: Forty patients with ID/DD/ASD referred to Nanshan Maternity and Child Health Care Hospital from September 2018 to January 2022 were enrolled. G-banded karyotyping analysis was carried out for the patients. Genomic DNA was extracted from peripheral blood samples and subjected to CNV-Seq analysis to detect chromosome copy number variations (CNVs) in such patients. ClinVar, DECIPHER, OMIM and other database were searched for data annotation. RESULTS: Among the 40 patients (including 30 males and 10 females), 16, 15 and 6 were diagnosed with ID, DD and ASD, respectively. One patient had combined symptoms of ID and DD, whilst the remaining two had combined ID and ASD. Four patients were found with abnormal karyotypes, including 47,XY,+mar, 46,XY,inv(8)(p11.2q21.2), 46,XX,del(5)(p14) and 46,XX[76]/46,X,dup(X)(p21.1q12). Chromosome polymorphism was also found in two other patients. CNV-seq analysis has detected 32 CNVs in 20 patients (50.0%, 20/40). Pathogenic CNVs were found in 10 patients (25.0%), 15 CNVs of uncertain clinical significance were found in 12 patients (30.0%), and 7 likely benign CNVs were found in 4 patients (10.0%). CONCLUSION Chromosome CNVs play an important role in the pathogenesis of ID/DD/ASD. CNV-seq can detect chromosomal abnormalities including microdeletions and microduplications, which could provide a powerful tool for revealing the genetic etiology of ID/DD/ASD patients.
Pregnancy ; Child ; Male ; Humans ; Female ; DNA Copy Number Variations ; Intellectual Disability/genetics* ; Autism Spectrum Disorder/genetics* ; Developmental Disabilities/genetics* ; Abnormal Karyotype

Humans ; Hemoglobinopathies ; Hemoglobins, Abnormal/genetics* ; Oxygen

OBJECTIVE: To investigate the possible causes of abnormal hemoglobin electrophoresis results. METHODS: The hemoglobin electrophoresis results of 5 696 patients in the First Affiliated Hospital of Chengdu Medical College from September 2018 to July 2021 were collected, and the abnormal results and clinical significance were analyzed. RESULTS: The results of 486 patients (accounting for 8.53%) were abnormal, of which 300 cases had increased HbA2, 135 cases had decreased HbA2, 44 cases had increased F alone, and 7 cases had abnormal hemoglobin bands. Among the 486 patients, 246 patients were thalassemia gene positive (the positive rate was 50.62%), including 29 cases of α thalassemia, 208 cases of β thalassemia and 9 cases of αβ thalassemia. Among the patients with elevated HbA2, 68.67% were detected β thalassemia, 3.00% αβ thalassemia, 9.33% were suspected to be caused by macrocytosis, 6.33% by thyroid dysfunction, and 12.67% by uncertainty of the method. Among the patients with reduced HbA2, 21.48% were detected α thalassemia, 60.00% iron deficiency anemia, 8.15% were suspected to be caused by thyroid dysfunction, and 10.37% by uncertainty of the method. Among the patients with elevated F alone, the results of thalassemia gene detection were negative, 40.91% of them were suspected to be caused by macrocytosis, 27.27% by hereditary persistence of fetal hemoglobin, 29.55% by special physiological condition of pregnant women, and 2.27% by hyperthyroidism. Abnormal hemoglobin bands were detected in 7 patients, including 4 cases of hemoglobin D, 2 cases of hemoglobin E, and 1 case of hemoglobin J. CONCLUSION Thalassemia, iron deficiency anemia, macrocytosis such as megaloblastic anemia and non-severe aplastic anemia, thyroid dysfunction, hereditary persistence of fetal hemoglobin, abnormal hemoglobin diseases, the uncertainty of the method are all important causes of abnormal hemoglobin electrophoresis results. In clinical work, the patient's indicators should be comprehensively analyzed to determine the possible cause.
Humans ; Female ; Pregnancy ; beta-Thalassemia/genetics* ; Anemia, Iron-Deficiency ; Fetal Hemoglobin/analysis* ; alpha-Thalassemia ; Blood Protein Electrophoresis ; Hemoglobin A2/analysis* ; Hemoglobins, Abnormal/analysis*

Hemoglobins, Abnormal ; Humans ; Singapore/epidemiology* ; alpha-Thalassemia

OBJECTIVE: To identify one case of rare Hb Lepore-BW associated with IVS-II-654 heterozygous mutation in Sichuan area. METHODS: The blood routine examination and hemoglobin electrophoresis methods were used to analyze the blood routine parameters, HbA₂ and HbF in the samples of peripheral blood in proband and his parents, as well as the cord blood of pregnant woman. The detection of thalassemia gene and Sanger sequencing methods were used to detect the hemoglobin mutations. RESULTS: The result showed that the Hb Lepore-BW heterozygous mutation was detected in the father of the proband, while a rare Hb Lepore-BW with IVS-II-654 heterozygous mutation was detected in the proband, as well as his mother and cord blood were both detected as IVS-II-654 heterozygous mutation. CONCLUSION The study identified a rare Hb Lepore-BW with IVS-II-654 heterozygous mutation, which was characterized by intermediate β-thalassemia. It is necessary to hemoglobin electrophoresis combined with routine blood testing in prenatal screening.
Female ; Hemoglobins, Abnormal/genetics* ; Heterozygote ; Humans ; Infant, Newborn ; Male ; Mutation ; Pregnancy ; Prenatal Diagnosis ; beta-Thalassemia/genetics*