Genetics of Wilson disease and Wilson‐like phenotype in a clinical series from eastern Spain

Sánchez‐Monteagudo, Ana; Alvarez-Saúco, M; Sastre, Isabel; Martínez‐Torres, Irene; Lupo, Vincenzo; Berenguer, Marina; Espinós, Carmen

doi:10.1111/cge.13719

Cited by 26 publications

(33 citation statements)

References 10 publications

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“…Genetic analyses were performed using a customized panel with 498 genes involved in movement disorders (MovDisord-498) as previously described [47] and following filtering data criteria formerly reported in [48].…”

Section: Genetics and Bioinformaticsmentioning

confidence: 99%

Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration

Sancho

Andrés-Bordería

Gorría-Redondo

et al. 2021

IJMS

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(1) Background: A non-progressive congenital ataxia (NPCA) phenotype caused by b-III spectrin (SPTBN2) mutations has emerged, mimicking spinocerebellar ataxia, autosomal recessive type 14 (SCAR14). The pattern of inheritance, however, resembles that of autosomal dominant classical spinocerebellar ataxia type 5 (SCA5). (2) Methods: In-depth phenotyping of two boys studied by a customized gene panel. Candidate variants were sought by structural modeling and protein expression. An extensive review of the literature was conducted in order to better characterize the SPTBN2-associated NPCA. (3) Results: Patients exhibited an NPCA with hypotonia, developmental delay, cerebellar syndrome, and cognitive deficits. Both probands presented with progressive global cerebellar volume loss in consecutive cerebral magnetic resonance imaging studies, characterized by decreasing midsagittal vermis relative diameter measurements. Cortical hyperintensities were observed on fluid-attenuated inversion recovery (FLAIR) images, suggesting a neurodegenerative process. Each patient carried a novel de novo SPTBN2 substitution: c.193A > G (p.K65E) or c.764A > G (p.D255G). Modeling and protein expression revealed that both mutations might be deleterious. (4) Conclusions: The reported findings contribute to a better understanding of the SPTBN2-associated phenotype. The mutations may preclude proper structural organization of the actin spectrin-based membrane skeleton, which, in turn, is responsible for the underlying disease mechanism.

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Section: Genetics and Bioinformaticsmentioning

confidence: 99%

Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration

Sancho

Andrés-Bordería

Gorría-Redondo

et al. 2021

IJMS

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“…Stratified genetic analysis is recommended in order to achieve a reasonable diagnostic success rate with the aim to cover the whole ATP7B sequence and the different possible mutation types [ 70 , 71 ]. First, it is advisable to perform the study of the 21 coding exons and flanking intron sequences, since they harbor the majority (~95%) of the clinical variants ( Table 2 ).…”

Section: A Mendelian Disease Caused By Mutations In Atp7bmentioning

confidence: 99%

Wilson’s Disease: Facing the Challenge of Diagnosing a Rare Disease

et al. 2021

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Wilson disease (WD) is a rare disorder caused by mutations in ATP7B, which leads to the defective biliary excretion of copper. The subsequent gradual accumulation of copper in different organs produces an extremely variable clinical picture, which comprises hepatic, neurological psychiatric, ophthalmological, and other disturbances. WD has a specific treatment, so that early diagnosis is crucial to avoid disease progression and its devastating consequences. The clinical diagnosis is based on the Leipzig score, which considers clinical, histological, biochemical, and genetic data. However, even patients with an initial WD diagnosis based on a high Leipzig score may harbor other conditions that mimic the WD’s phenotype (Wilson-like). Many patients are diagnosed using current available methods, but others remain in an uncertain area because of bordering ceruloplasmin levels, inconclusive genetic findings and unclear phenotypes. Currently, the available biomarkers for WD are ceruloplasmin and copper in the liver or in 24 h urine, but they are not solid enough. Therefore, the characterization of biomarkers that allow us to anticipate the evolution of the disease and the monitoring of new drugs is essential to improve its diagnosis and prognosis.

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“…Genetics analysis has the ability to provide early and accurate WD diagnosis. In a clinical series of WD in eastern Spain, Sánchez-Monteagudo et al identified biallelic ATP7B mutations in 30 patients, and in a case, a large deletion of exon 1 with MLPA (14). Our patient harbors a compound heterozygous mutation in the ATP7B gene.…”

Section: Discussionmentioning

confidence: 50%

Osteoarticular manifestations as initial symptoms of WD with novel compound heterozygote mutations in the ATP7B gene: a case report

Li¹,

Lü²,

Yu³

et al. 2021

Transl Pediatr

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Wilson disease (WD) is a rare autosomal recessive disease characterized by hepatic, neurologic and psychiatric, and variable manifestations. Skeletal and articular manifestations are usually overlooked at an early stage in WD patients, which have an effect on therapeutic outcome and prognosis. We report a 13-yearold girl of Chinese Han ethnicity with arthralgia and fracture as initial symptoms of WD. Laboratory tests showed her 1:80 of antinuclear antibodies (ANA). The patient was diagnosed with oligoarticular juvenile idiopathic arthritis (JIA) and treated with 10 mg of methotrexate (MTX) every week and diclofenac sodium every day. Her symptoms showed no improvement over 6 months and her medications were ceased. Then the patient presented to our department with a 3-week history dysarthria, gait abnormalities, dystonia and tremor. Kayser-Fleischer rings, serum ceruloplasmin and liver biopsy confirmed the diagnosis of WD. Genetic analysis was performed using SureSelect Clinical Research Exome v2 and then verified by bidirectional Sanger sequencing. We found that the patient carried a novel compound heterozygous mutation in ATPase copper transporting beta (ATP7B) on both chromosomes, which consist of a heterozygote of NM_000053.3 (ATP7B): c.3884C>T p. Ala1295Val and large fragment heterozygous deletion in exons 10-11 of ATP7B gene identified using multiplex ligation-dependent probe amplification (MLPA), to be inherited from her asymptomatic parents, respectively. The patient's symptoms were relieved at the 1-year followup after treatment with D-penicillamine and oral zinc. This case highlights that WD should be taken into consideration in adolescents with unexplained joint pain, arthritis, and fracture of the large joints.

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Genetics of Wilson disease and Wilson‐like phenotype in a clinical series from eastern Spain

Cited by 26 publications

References 10 publications

Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration

Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration

Wilson’s Disease: Facing the Challenge of Diagnosing a Rare Disease

Osteoarticular manifestations as initial symptoms of WD with novel compound heterozygote mutations in the ATP7B gene: a case report

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