Hb H disease associated with compound heterozygosity for -- deletion and a novel alpha globin chain variant (:c.175C>A) on the distal histidine in a Chinese family.

Objectives: In clinical practice, the majority of α-thalassaemia cases arise from deletions of the α-globin genes. However, a subset of cases is attributed to rare haemoglobin variants, which can manifest with borderline or normal screening results, potentially leading to missed diagnoses in clinical practice.

Methods: Blood samples were collected from family members and underwent haematological, DNA and RNA analysis.

Molecular spectrum and prevalence of thalassemia investigated by third-generation sequencing in the Dongguan region of Guangdong Province, Southern China.

Background: PCR, Sanger sequencing and NGS are often employed for carrier screening of thalassemia but all of these methods have limitations. In this study, we evaluated a new third-generation sequencing-based approach termed comprehensive analysis of thalassemia alleles (CATSA) to explore the prevalence of thalassemia in the Dongguan region of southern China.

Methods: 19,932 subjects were recruited for thalassemia screening and hemoglobin testing was performed for each of them.

[Results of carrier screening for Spinal muscular atrophy among 35 145 reproductive-aged individuals from Dongguan region].

Objective: To carry out carrier screening for Spinal muscular atrophy (SMA) in reproductive-aged individuals from Dongguan region and determine the carrier frequency of SMN1 gene mutations.

Methods: Reproductive-aged individuals who underwent SMN1 genetic screening at the Dongguan Maternal and Child Health Care Hospital from March 2020 to August 2022 were selected as the study subjects. Deletions of exon 7 and 8 (E7/E8) of the SMN1 gene were detected by real-time fluorescence quantitative PCR (qPCR), and prenatal diagnosis was provided for carrier couples by multiple ligation-dependent probe amplification (MLPA).

A stepwise haematological screening and whole-exome sequencing reveal multiple mutations from SUPT5H causing an elevation of Hb A from a cohort of 47336 individuals.

Introduction: Though an increase in Hb A is one of the most key markers of β-thal carriers, a few independent cases are reported to show elevated Hb A levels caused by mutations in other genes beyond β-globin gene.

Methods: We reviewed the haematological indices of 47336 individuals to analyse the phenotype-genotype correlation and identified 1439 individuals (3.04%) positive in the elevation of Hb A .

Quantification of human embryonic ζ-globin chains in Southeast Asian deletion (--) carriers.

Aims: Reactivation of embryonic ζ-globin is a promising strategy for genetic treatment of α-thalassaemia. However, quantification of ζ-globin as a quantitative trait in α-thalassaemia carriers and patients remains incompletely understood. In this study, we aimed to set up a reliable approach for the quantification of ζ-globin in α-thalassaemia carriers, followed by a population study to investigate its expression patterns.

Two large novel alpha-globin gene cluster deletions causing alpha(0)-thalassemia in two Chinese families.

Introduction: Monosomy of terminal 16p13.3 is a relatively common subtelomeric abnormality, most affected individuals presented α-thalassemia, some also have mental retardation, developmental abnormalities and/or speech delay and facial dysmorphism, which is termed ATR-16 syndrome. Here, we reported two novel 16p13.

Exome-based preconception carrier testing for consanguineous couples in China.

Objective: To evaluate the utility of clinical exome sequencing (ES)-based carrier screening in Chinese consanguineous couples.

Methods: Consanguineous couples were screened for autosomal recessive (AR) disorders using the clinical ES of 5000 genes associated with human diseases.

Results: We recruited 14 couples who elected to have sequencing.

Hyperhaemolysis in a pregnant woman with a homozygous β -thalassemia mutation and two genetic modifiers.

Introduction: Patients with a homozygous β -thalassemia mutation usually have a transfusion-dependent β-thalassemia major phenotype. However, some β-thalassemia patients present with a relatively mild and even normal phenotype and always have a high level of Hb F induced by genetic modifiers.

Methods: In this study, we identified a homozygous β -thalassemia mutation (HBB: c.

Analysis of tissue from pregnancy loss and aborted fetus with ultrasound anomaly using subtelomeric MLPA and chromosomal array analysis.

Objective: To evaluate the incidence and types of chromosomal abnormalities in pregnancy loss and aborted fetuses with anomaly and compare the performance of subtelomeric MLPA and chromosomal microarray analysis (CMA) in these specimens.

Methods: Samples were collected from spontaneous miscarriages, stillbirths and aborted fetuses with anomaly between January 2015 and April 2019. Chromosomal abnormalities were detected using subtelomeric MLPA and CMA.

Xp11.22 duplications in four unrelated Chinese families: delineating the genotype-phenotype relationship for HSD17B10 and FGD1.

Background: Xp11.22 duplications have been reported to contribute to nonsyndromic intellectual disability (ID). The HUWE1 gene has been identified in all male Xp11.

Tetrasomy 18p Case Report.

Background: Tetrasomy 18p is a rare disorder. It is known to affect about 250 families worldwide. Tetrasomy 18p is also the most common type of isochromosome.

Molecular and Hematological Characterization of a Novel Translation Initiation Codon Mutation of the α2-Globin Gene (AT>AT or : c.3G>C).

Although mutations causing α-thalassemia (α-thal) are mainly larger deletions involving one or both of the duplicated α-globin genes, point mutations are not rare. We have identified a novel mutation of the translation initiation codon of the α2-globin gene with DNA sequencing and allele-specific multiplex ligation-dependent probe amplification (MLPA) in a Chinese family. RNA analysis was performed with reverse transcription-MLPA (RT-MLPA).

Polymorphisms of α-Globin Genes Compromise Polymerase Chain Reaction-Based α-Thalassemia Genotyping in Three Chinese Families.

In practice, gap-polymerase chain reaction (gap-PCR) and reversed dot-blot are the two most frequently used molecular diagnostic methods for α-thalassemia (α-thal) genotyping. Here, we describe three Chinese individuals from three unrelated families in whom a polymorphism on the α-globin gene cluster led to diagnostic pitfalls. During general molecular diagnosis of thalassemia, three individuals with unexplained results were found.

Can cell-free DNA testing be used in pregnancies with isolated fetal omphalocele? Preliminary evidence from cytogenetic results of prenatal cases.

To evaluate whether cell-free DNA (cfDNA) testing could replace an invasive procedure in pregnancies with isolated fetal omphalocele. This was a retrospective study of all pregnancies with sonographically detected fetal omphalocele at three tertiary referral centers between 2012 and 2016. Invasive diagnostic testing was performed for genetic investigations using conventional karyotyping or chromosomal microarray.

Prenatal findings and molecular cytogenetic analyses of a de novo interstitial deletion of 1q23.3 encompassing PBX1 gene.

Objectives: To present the prenatal findings and the molecular cytogenetic analyses of a de novo interstitial deletion of 1q23.3 encompassing PBX1 gene.

Case Report: A 32-year-old woman (gravida 1, para 0) underwent amniocentesis at 26 weeks' gestation because of constant small fetal kidneys on prenatal ultrasound.

Hb H Disease Results from Compound Heterozygosity of - - and -α in a Chinese Family.

The α-thal deletion of 3.557 kb (NG_000006.1: g.

[Rapid preimplantation genetic diagnosis of -thalassemia SEA deletion with blastocyst cell whole genome amplification and short fragment Gap-PCR method].

Objective: To develop a rapid preimplantation genetic diagnosis method for -thalassemia SEA deletion based on blastocyst cell whole genome amplification (WGA) combined with short fragment Gap-PCR.

Methods: Using multiple displacement amplification (MDA) WGA technique, we established a double-fluorescent PCR system of the housekeeping genes GAPDH and β-actin for WGA quality testing, and a genotyping PCR system of mutant and normal short sequences for α-thalassemia SEA deletion. The sensitivity and accuracy of this method for diagnosis of -thalassemia SEA deletion were evaluated by detecting lymphocyte samples containing different cell numbers from carriers of SEA deletion.

Molecular and Hematological Characterization of Two Novel δ-Globin Gene Mutations Found in Chinese Individuals.

We identified two novel δ-globin gene mutations in two families during routine thalassemia screening. One missense mutation at codon 73 on the δ-globin gene [δ73(E17)Asp→Val, HBD: c.221A>T] which results in a Hb A variant homologous to the β-globin gene variant called Hb Mobile [β73(E17)Asp→Val, HBB: c.

Rapid and simultaneous detection of common aneuploidies by quadruplex real-time polymerase chain reaction combined with melting curve analysis.

Background: During the prenatal period, the number variation of chromosomes 13, 18, 21, X and Y accounts for more than 80% of the clinically significant chromosomal abnormalities diagnosed. Rapid tests for prenatal diagnosis of these abnormalities can improve pregnancy management and alleviate parental anxiety. Here, we present a molecular alternative method for detecting common aneuploidies.

[Analysis of the cause of pregnancy failure with combined MLPA assay for subtelomeric regions and ultrasonography].

Objective: To explore the value of multiplex ligation-dependent probe amplification (MLPA) for the detection of chromosome abnormalities in miscarriage tissues, and to correlate the result with ultrasound findings.

Methods: A total of 421 cases of spontaneous abortions and fetal deaths were detected with the MLPA method.

Results: Among the 421 samples, 232 (55.

Fetal Anemia and Hydrops Fetalis Associated with Homozygous Hb Constant Spring (HBA2: c.427T > C).

Hb Constant Spring (Hb CS, HBA2: c.427T > C) is a common nondeletional α-thalassemia (α-thal) that results from a nucleotide substitution at the termination codon of the α2-globin gene. Homozygosity for Hb CS (α(CS)α/α(CS)α) is relatively rare, and generally characterized with mild hemolytic anemia, jaundice, and splenomegaly.

Rapid detection of α-thalassaemia alleles of --(SEA)/, -α(3.7)/ and -α(4.2)/ using a dual labelling, self-quenching hybridization probe/melting curve analysis.

Objectives: The aim of the study was to set up an alternative automatic molecular diagnostic method for deletional α-thalassaemia mutations without gel electrophoresis.

Methods: Based on the sequence variation within the two Z boxes and melting curve analysis of dually labelled probes, a real-time PCR assay was developed and validated for the rapid detection of major α-genotypes (--(SEA)/αα, --(SEA)/-α(3.7), --(SEA)/-α(4.

Prevalence and molecular characterization of structural hemoglobin variants in the Dongguan region of Guangdong province, southern China.

The aim of the present study was to find the most prevalent structural hemoglobin (Hb) variants in southern China and to present hematological and molecular data of abnormal Hbs in the population from southern China. The type and frequency of structural Hb variants and their hematological and molecular characteristics were identified in 131 individuals from 30,848 unrelated partners who were referred to the prenatal clinic of Dongguan Maternal & Children Health Hospital, Dongguan, Guangdong, People's Republic of China (PRC) from 2011 to 2013. α-Globin or β-globin chain variants were screened using a capillary electrophoresis (CE) system, and α-globin or β-globin gene mutations were confirmed using sequencing techniques.

Delineation of the molecular basis of borderline hemoglobin A2 in Chinese individuals.

Background: The "gray zone" of borderline hemoglobin A2 (Hb A2) may be present in a large section of the population, especially in countries where thalassemia is common. However, very little is currently known of the molecular basis of borderline Hb A2 in Chinese individuals.

Method: In this study, we performed a comprehensive analysis of the globin genotypes and KLF1 gene mutations associated with borderline Hb A2 in 165 Chinese subjects.