Genomic Variations in ATP7B Gene in Indian Patients with Wilson Disease

Nagral, Aabha; Mallakmir, Snehal; Garg, Naveen; Tiwari, Kritika; Masih, Suzena; Nagral, Nishtha; Unavane, Ojas; Jhaveri, Ajay; Phadke, Shubha R.; Arunkumar, Ganeshprasad; Aggarwal, Rakesh

doi:10.1007/s12098-022-04250-9

Cited by 5 publications

(2 citation statements)

References 28 publications

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“…In other populations and territories of the world, other clusters of pathogenic variants are characteristic and are detected mainly in exons 2, 5, 8, 14, 15, 16, and 18 of the gene. Thus, in patients with WD living in different countries, the following predominate in the spectrum of pathogenic variants of the ATP7B gene options: p.Met645Arg-in Spain [23,63], p.Met769HisfsTer26-in Hong Kong and Taiwan [69], p.Pro992Leu and p.Arg778Leu-in other countries of East Asia and China [26,70], p.Ala803Thr and p.Arg778Leu-in Japan [26,70], p.Thr1232Pro-in Colombia [71], p.Arg969Gln, p.Leu936STOP, p.Ile1148Thr, and p.His1069Gln-in Greece [72], p.Ala1135GlnfsTer13-in Brazil and Venezuela [73], p.Pro992Leu, c.2977insA, and c.3031insA (in exons 18 and 13)-in Northern India, p.Cys271 STOP-in Eastern India, p.Gly1061Glu and p.Cys271STOP-in South India [74], c.del441-427-in Sardinia [13], p.Ser744Pro and p.Glu1399Arg in the complete absence of European and Asian major pathogenic variants-in Pakistan and Saudi Arabia [75], and c.2299insC, p.Gly710Ser, p.Ala1135GlnfsTer13 (in exon 15), and p.Arg969Gln (in exon 13)-in Central, Eastern, and Northern Europe [21]. In 2012, a new pathogenic variant of the ATP7B gene in exon 9 was described in patients in Austria [76], Table 3 shows data on the frequency of pathogenic variants in the ATP7B gene, characteristic of different countries (according to Chang I., 2017) [71].…”

Section: Discussionmentioning

confidence: 99%

Epidemiology of Wilson’s Disease and Pathogenic Variants of the ATP7B Gene Leading to Diversified Protein Disfunctions

Ovchinnikova,

Garbuz,

Ovchinnikova

et al. 2024

IJMS

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Wilson’s disease (WD) is an autosomal recessive disorder characterized by toxic accumulation of copper in the liver, brain, and other organs. The disease is caused by pathogenic variants in the ATP7B gene, which encodes a P-type copper transport ATPase. Diagnosing WD is associated with numerous difficulties due to the wide range of clinical manifestations and its unknown dependence on the physiological characteristics of the patient. This leads to a delay in the start of therapy and the subsequent deterioration of the patient’s condition. However, in recent years, molecular genetic testing of patients using next generation sequencing (NGS) has been gaining popularity. This immediately affected the detection speed of WD. If, previously, the frequency of this disease was estimated at 1:35,000–45,000 people, now, when conducting large molecular genetic studies, the frequency is calculated as 1:7026 people. This certainly points to the problem of identifying WD patients. This review provides an update on the performance of epidemiological studies of WD and describes normal physiological functions of the protein and diversified disfunctions depending on pathogenic variants of the ATP7B gene. Future prospects in the development of WD genetic diagnostics are also discussed.

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Section: Discussionmentioning

confidence: 99%

Epidemiology of Wilson’s Disease and Pathogenic Variants of the ATP7B Gene Leading to Diversified Protein Disfunctions

Ovchinnikova,

Garbuz,

Ovchinnikova

et al. 2024

IJMS

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“…However, this method does not allow for the detection of mutations in intron regions, which occur in about 2% of patients with WD [ 34 ]. A direct molecular study of WD is recommended due to the diversity of its clinical manifestations and the limitations of modern markers [ 35 ]. It also allows for the creation of flexible and efficient mutation screening strategies for certain populations.…”

Section: Discussionmentioning

confidence: 99%

Design, Optimization and Validation of the ARMS PCR Protocol for the Rapid Diagnosis of Wilson’s Disease Using a Panel of 14 Common Mutations for the European Population

Garbuz

Ovchinnikova

Kumeiko

2022

Genes

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Background: Wilson’s disease (WD) is an autosomal recessive inherited disorder of copper metabolism resulting from various mutations in the ATP7B gene. Despite good knowledge and successful treatment options, WD is a severe disease that leads to disability, destructively affecting the quality of life of patients. Currently, none of the available laboratory tests can be considered universal and specific for the diagnosis of WD. Therefore, the introduction of genetic diagnostic methods that allow for the identification of the root cause at any stage over the course of the disease gave hope for an earlier solution of diagnostic issues in patients with WD. Methods: A method for the genetic diagnosis of WD based on ARMS PCR, DreamTaq Green PCR Master Mix and modified primers has been developed. This method is able to detect 14 mutant alleles: p.His1069Gln, p.Glu1064Lys, p.Met769HisfsTer26, p.Gly710Ser, p.Ser744Pro, p.Ala1135GlnfsTer13, p.Arg778Leu, p.Arg1041Trp, p.Arg616Gln, p.Arg778Gly, p.Trp779*, p.Val834Asp, p.Gly943Ser and p.3222_3243+21del43. Results: The primers for all mutations were highly specific with an absence of wild-type amplification. All the results were validated by direct DNA Sanger sequencing. Conclusions: This fast and economical method provides coverage for the identified common mutations, thereby making ARMS PCR analysis using DreamTaq Green PCR Master Mix and modified primers feasible and attractive for large-scale routine use.

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