Novel α<sup>0</sup>-Thalassemia Deletion Identified in an Indian Infant with Hb H Disease

Moore, Jordyn; Pullon, Beverley M.; Drake, Kylie M.; Brennan, Stephen O.

doi:10.1080/03630269.2020.1797774

Cited by 3 publications

(3 citation statements)

References 14 publications

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“…Recently, a novel α 0 thalassemia large deletion removing both HBA2 and HBA1 along with the 3.7 kb deletion has been identified in a three month old Indian infant residing in New Zealand, which led to Hb H disease. The clinical presentation was similar to most other cases with hypochromic microcytic anemia and pallor [25].…”

Section: Resultssupporting

confidence: 77%

Molecular Heterogeneity of Hb H Disease in India

Thaker

Mahajan

Mukherjee

et al. 2022

Thalassemia Reports

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Alpha thalassemia is an autosomal recessive disorder caused by large deletions and/or point mutations in the α- globin genes. Hemoglobin H (Hb H) disease is most frequently due to deletion of three of the four α globin genes associated with variable clinical severity depending on the genotype. There are few reports on Hb H disease in Indians where genotyping has been done and we have reviewed the molecular and clinical heterogeneity of these cases. An electronic search for relevant articles was conducted using two journal databases, i.e., PubMed and Science Direct using the key words “Hb H Disease”, “Hemoglobin H”, “α-thalassemia”, “mutations”, “molecular heterogeneity”, “case reports” and “India”. This review was performed based on preferred reporting items for the systematic review and meta-analysis protocols (PRISMA-P) guidelines. The molecular spectrum of Hb H disease in Indians includes the most common [-α3.7, -α4.2, --SA, Poly A (AATAAA→AATA--), Hb Sallanches], rare [--SEA, --MED, IVS 1nt 1 (G→A), Hb Koya Dora, Hb Sun Prairie], very rare [Hb Iberia, Hb Seal Rock, Hb Zürich-Albisrieden] and novel [Codon 76 (+T) and --Kol] α-globin gene mutations inherited largely as compound heterozygotes with considerable clinical variability. The molecular diagnosis of Hb H disease is important for genetic counseling and management.

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Section: Resultssupporting

confidence: 77%

Molecular Heterogeneity of Hb H Disease in India

Thaker

Mahajan

Mukherjee

et al. 2022

Thalassemia Reports

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“…Chromosome 16 is 90Mb in length and contains 835 coding genes. Many of these genes have been linked to diseases, such as prenatal growth retardation [27], abnormal fetal head circumference [28], thalassemia [29] and autism [30]. The CNVs in chromosome 16 were increasingly found to serve a clear role in the determination of developmental delay [31].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Copy-Number Variations and Possible Candidate Genes in Recurrent Pregnancy Losses

Sheng

Hou

et al. 2021

Genes

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It is well established that embryonic chromosomal abnormalities (both in the number of chromosomes and the structure) account for 50% of early pregnancy losses. However, little is known regarding the potential differences in the incidence and distribution of chromosomal abnormalities between patients with sporadic abortion (SA) and recurrent pregnancy loss (RPL), let alone the role of submicroscopic copy-number variations (CNVs) in these cases. The aim of the present study was to systematically evaluate the role of embryonic chromosomal abnormalities and CNVs in the etiology of RPL compared with SA. Over a 3-year period, 1556 fresh products of conception (POCs) from miscarriage specimens were investigated using single nucleotide polymorphism array (SNP-array) and CNV sequencing (CNV-seq) in this study, along with further functional enrichment analysis. Chromosomal abnormalities were identified in 57.52% (895/1556) of all cases. Comparisons of the incidence and distributions of chromosomal abnormalities within the SA group and RPL group and within the different age groups were performed. Moreover, 346 CNVs in 173 cases were identified, including 272 duplications, 2 deletions and 72 duplications along with deletions. Duplications in 16q24.3 and 16p13.3 were significantly more frequent in RPL cases, and thereby considered to be associated with RPL. There were 213 genes and 131 signaling pathways identified as potential RPL candidate genes and signaling pathways, respectively, which were centered primarily on six functional categories. The results of the present study may improve our understanding of the etiologies of RPL and assist in the establishment of a population-based diagnostic panel of genetic markers for screening RPL amongst Chinese women.

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“…In addition, the test mutations of the routine kits are limited. If a rare or novel large fragment deletion is suspected, multiplex ligation‐dependent probe amplification (MLPA) screening is first required, followed by Gap‐PCR amplification, and then Sanger sequencing determines the break sites 21 . However, as presented in this study, LMS provided a rapid and more effective method for identifying the common Hb H genotype and enabled the detection of the rare Hb H genotype.…”

Section: Discussionmentioning

confidence: 92%

Detection of hemoglobin H disease by long molecule sequencing

Liang

Qin

et al. 2022

Clinical Laboratory Analysis

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Background Hemoglobin H (Hb H) disease is a moderate‐to‐severe form of α‐thalassemia (α‐thal), and parts of patients may require intermittent transfusion therapy, especially during intercurrent illness. However, rare Hb H diseases remain undetected using routine methods being outside of the testing scope. In this study, we present an approach to detecting Hb H disease by long molecule sequencing (LMS). Methods A total of 206 known genotype samples were collected and carried to blind detected by LMS on the PacBio Sequel platform. Circular consensus sequencing reads were aligned to the hg19 reference genome using Free‐Bayes finished LMS. LMS accuracy would be compared with routine methods, including Gap‐PCR and PCR‐Reverse dot blot hybridization (PCR–RDB). Results The assay could detect carriers of both deletion and point mutations. It had an overall accuracy of 100% when compared with routine methods. In addition, LMS detected six mutations based on routine methods and corrected three case results. Hb H diseases were identified using LMS, whether a common or rare genotype, a deletion or non‐deletion genotype. However, two cases of Hb H disease were misdiagnosed using routine methods. Conclusions Long molecule sequencing can be suggested as a rapid and reliable assay to detect probable carriers of hemoglobinopathies. LMS accurately identified the common and rare genotypes of Hb H disease.

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Novel α⁰-Thalassemia Deletion Identified in an Indian Infant with Hb H Disease

Cited by 3 publications

References 14 publications

Molecular Heterogeneity of Hb H Disease in India

Molecular Heterogeneity of Hb H Disease in India

Characterization of Copy-Number Variations and Possible Candidate Genes in Recurrent Pregnancy Losses

Detection of hemoglobin H disease by long molecule sequencing

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Novel α0-Thalassemia Deletion Identified in an Indian Infant with Hb H Disease

Cited by 3 publications

References 14 publications

Molecular Heterogeneity of Hb H Disease in India

Molecular Heterogeneity of Hb H Disease in India

Characterization of Copy-Number Variations and Possible Candidate Genes in Recurrent Pregnancy Losses

Detection of hemoglobin H disease by long molecule sequencing

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Novel α⁰-Thalassemia Deletion Identified in an Indian Infant with Hb H Disease