Novel variants of <i>CYP21A2</i> in Vietnamese patients with congenital adrenal hyperplasia

Dũng, Vũ Chí; Tran, Thinh Huy; Nguyễn, Đức Hinh; Luong, Long Hoang; Le, Phuong Thi; Ta, Minh Hieu; Ngo, Huong Thi Thanh; Nguyen, Mai P.; Le‐Anh, Tuan P.; Nguyen, Duc Minh; Bui, The‐Hung; Ta, Van Thanh; Tran, Van Khanh

doi:10.1002/mgg3.623

Cited by 10 publications

(4 citation statements)

References 33 publications

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“…Using the MLPA technique, the prevalence of large deletions and large gene conversions in the present study was found in 29/112 (25.9%) patients with the SW phenotype. The results were in agreement with the work of Ben Charfeddine et al, 2012, who reported gene deletion/conversion in 11/50 Tunisian patients (22%) ( Kharrat et al, 2004 ; Ben Charfeddine et al, 2012 ; Chi et al, 2019 ; Umaña-Calderón et al, 2021 ).…”

Section: Discussionsupporting

confidence: 93%

Copy Number Variations in Genetic Diagnosis of Congenital Adrenal Hyperplasia Children

et al. 2022

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Background: Congenital adrenal hyperplasia (CAH) is a monogenic disorder caused by genetic diversity in the CYP21A2 gene, with 21-hydroxylase deficiency (21-OHD) as the most common type. Early sex assignment and early diagnosis of different genetic variations with a proper technique are important to reduce mortality and morbidity. Proper early sex identification reduces emotional, social, and psychological stress.Aim: Detection of a spectrum of aberrations in the CYP21A2 gene, including copy number variations, gene conversion, chimeric genes, and point variations.Methods: The CYP21A2 gene was screened using MLPA assay in 112 unrelated Egyptian children with 21-OHD CAH (33 males and 79 females).Results: In the studied group, 79.5% were diagnosed within the first month of life. 46.8% of the genetic females were misdiagnosed as males. Among the copy number variation results, large deletions in 15.4% and three types of chimeric genes in 9% (CH-1, CH-7, and CAH-X CH-1) were detected. Regarding gene dosage, one copy of CYP21A2 was found in 5 cases (4.5%), three copies were detected in 7 cases (6.3%), and one case (0.9%) showed four copies. Eight common genetic variants were identified, I2G, large deletions, large gene conversion (LGC), I172N, F306 + T, -113 SNP, 8bp Del, and exon 6 cluster (V237E and M239K) with an allelic frequency of 32.62%, 15.45%, 7.30%, 3.00%, 2.58%, 2.15%, 0.86%, and 0.86%, respectively.Conclusion: High prevalence of copy number variations highlights the added value of using MLPA in routine laboratory diagnosis of CAH patients.

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Section: Discussionsupporting

confidence: 93%

Copy Number Variations in Genetic Diagnosis of Congenital Adrenal Hyperplasia Children

et al. 2022

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“…The prevalence of CAH has increased nationally, with an estimated increase from 150 children at NHP in Hanoi in 2004 to 1235 cases (325 with genotyping completed) in 2018 [ 62 ], representing a 723% increase over 14 years. Vietnam’s national NBS program now includes CAH (together with congenital hypothyroidism, glucose-6-phosphate dehydrogenase deficiency, galactosemia, phenylketonuria and other inborn errors of metabolism) and has determined the incidence of CAH in Vietnam at 1:9008 live births [ 63 ].…”

Section: Resultsmentioning

confidence: 99%

“…Molecular diagnosis assists with genetic counselling, and is strengthening diagnostic capacity [ 64 ]. A recent publication from Vietnam on genetic analysis of 212 people living with CAH reported six novel variants [ 62 ].…”

Section: Resultsmentioning

confidence: 99%

We All Have a Role to Play: Redressing Inequities for Children Living with CAH and Other Chronic Health Conditions of Childhood in Resource-Poor Settings

Armstrong

Yap²,

Chan-Cua

et al. 2020

IJNS

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CLAN (Caring and Living as Neighbours) is an Australian-based non-governmental organisation (NGO) committed to equity for children living with chronic health conditions in resource-poor settings. Since 2004, CLAN has collaborated with a broad range of partners across the Asia Pacific region to improve quality of life for children living with congenital adrenal hyperplasia (CAH). This exploratory case study uses the Knowledge to Action (KTA) framework to analyse CLAN’s activities for children living with CAH in the Asia Pacific. The seven stages of the KTA action cycle inform a systematic examination of comprehensive, collaborative, sustained actions to address a complex health challenge. The KTA framework demonstrates the “how” of CLAN’s approach to knowledge creation and exchange, and the centrality of community development to multisectoral collaborative action across a range of conditions, cultures and countries to redressing child health inequities. This includes a commitment to: affordable access to essential medicines and equipment; education, research and advocacy; optimisation of medical management; encouragement of family support groups; efforts to reduce financial burdens; and ethical, transparent program management as critical components of success. Improvements in quality of life and health outcomes are achievable for children living with CAH and other chronic health conditions in resource-poor settings. CLAN’s strategic framework for action offers a model for those committed to #LeaveNoChildBehind.

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“…Studies from the USA, UK, Cuba, Vietnam, China, Sweden have reported the I2G splice variant as the most common pseudogene-derived mutation in their study cohorts [25][26][27][28][29][30]. In a mixed population study, New Maria I. et al reported I2G and V281Lmutations to be the prominent mutations identi ed in the largest cohort of 1507 subjects [31].…”

Section: Discussionmentioning

confidence: 99%

Allele-specific PCR and Next-generation sequencing based genetic screening for Congenital Adrenal Hyperplasia in India

Ravichandran

Korula

Asha

et al. 2021

European Journal of Medical Genetics

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Genotyping CYP21A2 gene is known to be extremely challenging and is not utilized as a rst tier diagnostic tool in routine clinical practice. Also, with the advent of massive parallel sequencing technology, there is a need for investigating extended panel of genes implicated in CAH. This study aims to establish a comprehensive genetic screening strategy for ve genes in CAH. MethodsAllele-Speci c Polymerase Chain Reaction (ASPCR) for hotspot mutations in CYP21A2 gene followed by targeted Next-Generation Sequencing (NGS) of CYP21A2, CYP11B1, CYP17A1, POR, and CYP19A1 genes were carried out to screen 72 clinically diagnosed CAH subjects from India. ResultsUtilizing ASPCR, 88.7% (n = 55/62) of the subjects suspected with 21 hydroxylase de ciency were positive for CYP21A2 hotspot mutations. Utilizing NGS, the ASPCR assay was found to highly sensitive and speci c for screening these hotspot mutations. Additionally, through targeted NGS, six study subjects were positive for other CYP21A2 variants: one with a novel c.1274G > T, three with c.1451G > C and one with c.143A > G variant. One subject was compound heterozygous for c.955C > T/c.1042G > A variants identi ed using ASPCR and NGS. One subject suspected for a simple virilizing 21-hydroxylase de ciency was positive for a CYP19A1:c.1142A > T variant. CYP11B1 variants (c.1201-1G > A, c.1200 + 1delG, c.412C > T, c.1024C > T, c.1012dup, c.623G > A) were identi ed in all six subjects suspected for 11 beta-hydroxylase de ciency. ConclusionWith an overall mutation-positivity rate of 97.2% (140/144 alleles), ASPCR followed by a multigene targeted NGS assay has shown to be highly sensitive and speci c as a cost-effective and comprehensive diagnostic tool for CAH in a clinical setting.

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Novel variants of CYP21A2 in Vietnamese patients with congenital adrenal hyperplasia

Cited by 10 publications

References 33 publications

Copy Number Variations in Genetic Diagnosis of Congenital Adrenal Hyperplasia Children

Copy Number Variations in Genetic Diagnosis of Congenital Adrenal Hyperplasia Children

We All Have a Role to Play: Redressing Inequities for Children Living with CAH and Other Chronic Health Conditions of Childhood in Resource-Poor Settings

Allele-specific PCR and Next-generation sequencing based genetic screening for Congenital Adrenal Hyperplasia in India

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