Identification and characterization of a novel 43-bp deletion mutation of the ATP7B gene in a Chinese patient with Wilson’s disease: a case report

Liu, Gang; Ma, Dong‐Lai; Cheng, Jian; Zhang, Jingjing; Luo, Chen; Sun, Yun; Hu, Ping; Wang, Yuguo; Jiang, Tao; Xu, Zhengfeng

doi:10.1186/s12881-018-0567-z

Cited by 4 publications

(4 citation statements)

References 33 publications

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“…Microhomology sequences that are closely associated with deletion mutations in the vicinity of deletion breakpoints have previously been reported in the ATP7B gene, including c.51 + 384_1708-953del (21), c.1870-45_2355 + 189del (22), c.4021 + 87_4125-2del (23), c.3556 + 281_4001del, c.3134_3556 + 689del (24), c.532_574del (25), c.52-9329_1286-11del, c.2447 + 1612_2730 + 31delins12bp and c.3700-592_*409del (26). Alu repeat elements related to deletion events have also been discovered in the ATP7B gene [c.3134_3556 + 689del (24) and c.52-2671_368del (27)].…”

Section: Discussionmentioning

confidence: 88%

A novel gross deletion and breakpoint junction sequence analysis of ATP7B in a Chinese family with Wilson disease using next‑generation sequencing and Sanger sequencing

Liu

et al. 2019

Mol Med Report

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Wilson disease (WD) is a rare autosomal recessive genetic disorder that causes abnormal copper metabolism, resulting in pathological accumulation of copper in the liver, brain and other organs. Mutations in the ATPase copper transporter 7B (ATP7B) gene, which encodes a membrane P-type adenosine triphosphatase, have been identified as being responsible for WD. The present study analyzed clinical data and collected DNA samples from a pediatric patient with WD and her healthy parents. Mutation screening for ATP7B was performed using direct sequencing, multiplex ligation-dependent probe amplification(MLPA), next-generation sequencing (NGS) and Sanger sequencing of the breakpoint junction sequence. The patient (age, 2.7 years) presented with early-onset hepatic disease. The present study identified compound heterozygous mutations of ATP7B, including a heterozygous mutation (p.Arg1,041Trp) and a novel heterozygous gross deletion of a 57,771 bp fragment (chr13: 52490972-52548742) (GRCh37) from partial exon2- exon21 to external ATP7B sequence (15.833bp) in the patient. Analysis of the family members of the patient showed that the missense mutation and the gross deletion mutation were inherited from her mother and father, respectively. Microhomology and inverted repeat sequences, which may mediate the deletion mutation, were identified through sequence analysis on both sides of the breakpoints of this deletion. The present study provided additional information on the genotypic spectrum of the ATP7B gene, particularly with regard to early onset hepatic disease, as observed in the present patient with WD. The identification of the precise breakpoint junction sequence warrants further investigation of DNA break and recombination mechanisms. In detecting precise deletions, the NGS associated with Sanger sequencing of breakpoint junction sequence have been found to have more advantages than MLPA.

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Section: Discussionmentioning

confidence: 88%

A novel gross deletion and breakpoint junction sequence analysis of ATP7B in a Chinese family with Wilson disease using next‑generation sequencing and Sanger sequencing

Liu

et al. 2019

Mol Med Report

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“…Thus, being a genetic disorder, family history plays a critical role in the diagnosis. However, in some cases, there may not be a family history of the disease or the disease may be caused by a de novo mutation [15]. In these cases, a thorough clinical evaluation and genetic testing may be necessary to confirm the diagnosis.…”

Section: Discussion and Literature Reviewmentioning

confidence: 99%

Addressing the Challenges in the Diagnosis and Management of Pediatric Wilson’s Disease—Case Report and Literature Review

et al. 2023

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Wilson’s disease (WD) is an autosomal recessive disorder, in which the metabolism of copper is affected by metal accumulation in several organs that causes gradual organ degeneration. Since Wilson’s initial description of WD over a century ago, there have been significant improvements in understanding and managing the condition. Nevertheless, the ongoing gap between the onset of symptoms and diagnosis highlights the difficulties in identifying this copper overload disorder early. Despite being a treatable condition, detecting WD early remains a challenge for healthcare professionals at all levels of care, likely due to its rarity. The key challenge is, therefore, to educate physicians on how to identify atypical or infrequent symptoms of WD, prompting them to consider the diagnosis more carefully. The purpose of our review is to draw attention to the difficulties associated with diagnosing pediatric WD, starting from our personal experience of a complex case and then examining relevant literature. In summary, the diagnosis of WD in children is intricate and requires a heightened level of suspicion to identify this infrequent condition. A thorough evaluation by a multidisciplinary team of physicians, along with genetic testing, histopathologic examination, and specialized imaging studies, may be necessary to confirm the diagnosis and guide treatment.

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“…Wilson's disease (WD), an autosomal recessive disorder that impairs copper metabolism, affects the ATP7B gene [ 1 ]. Copper tends to build up in the liver, brain, kidneys, and cornea in WD, leading to a variety of symptoms including hepatic illness, neuronal degeneration in the brain, and Kayser-Fleischer (KF) rings at the corneal limbus [ 2 ]. An indication of WD includes low copper levels in the blood and ceruloplasmin, increased excretion of copper in the urine, and increasing hepatic copper levels [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Wilson's Disease Manifestation in Late Adulthood: A Case Report and Literature Review

Tazin¹,

Kumar²,

Orlang³

2022

Cureus

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Wilson's disease is a rare inherited condition that results in an excessive copper buildup in various organs, especially the liver, brain, and other vital organs, leading to cirrhosis, liver failure, neurological problems like involuntary movements, clumsy gait, speech difficulties, and psychological issues, in addition to other symptoms. It is an ATP7B gene mutation-driven autosomal recessive condition. Although the condition is present from birth, symptoms often start to show up between the ages of five and 35, when the body has accumulated enough copper. Wilson's disease may become fatal if an excessive amount of copper is accumulated in the body. It is treatable and has a good prognosis if diagnosed early. Early identification, however, is not always straightforward since symptoms might resemble those of other diseases and develop later in life when copper is absorbed by food and drink and gradually accumulates in the body's many organs. In addition to medicine, physicians advise people with Wilson's disease to avoid foods and beverages containing copper. Our patient was diagnosed with Wilson's disease at the age of 16 and was on Cuprimine which helped her to survive. Her younger sister was diagnosed at an early age and was started on a treatment regimen, which is why her sister's manifestation of Wilson's disease was less severe than hers.

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Identification and characterization of a novel 43-bp deletion mutation of the ATP7B gene in a Chinese patient with Wilson’s disease: a case report

Cited by 4 publications

References 33 publications

A novel gross deletion and breakpoint junction sequence analysis of ATP7B in a Chinese family with Wilson disease using next‑generation sequencing and Sanger sequencing

A novel gross deletion and breakpoint junction sequence analysis of ATP7B in a Chinese family with Wilson disease using next‑generation sequencing and Sanger sequencing

Addressing the Challenges in the Diagnosis and Management of Pediatric Wilson’s Disease—Case Report and Literature Review

Wilson's Disease Manifestation in Late Adulthood: A Case Report and Literature Review

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