Aug 2026· Frontiers in Neurology· Vol 17· 0 citations· 38 references
Medicine
TL;DR
A novel deletion variant in a Wilson disease patient harboring compound heterozygous variants in ATP7B is identified, expanding the known spectrum of pathogenic ATP7B variants.
Abstract
Introduction Wilson disease is an autosomal recessive monogenic disorder caused by mutations in the copper-transporting P-type ATPase beta gene (ATP7B) located on human chromosome 13. This gene encodes copper-transporting P-type ATPase. This article reports a case of Wilson disease with a novel ATP7B deletion variant. Case report We report a case of Wilson disease in a Chinese female patient. Cirrhosis was detected during routine examination at the age of 24 and was accompanied by reduced serum ceruloplasmin levels. At the age of 27, she gradually developed tremors and dystonia. Brain magnetic resonance imaging (MRI) revealed abnormal signals in the basal ganglia. Genetic testing for ATP7B was performed on the patient and her family members. Results Genetic testing revealed that the patient harbored compound heterozygous variants, including a previously reported c.1543+40G>A variant and a novel c.837delT variant in exon 2, which has not been previously reported. The c.1543+40G>A variant is registered in the ClinVar database with conflicting interpretations of pathogenicity (likely pathogenic/likely benign), The c.837delT variant is predicted to result in a frameshift (p.Ile279Metfs*5), introducing a premature termination codon, and is thus likely to impair the function of the copper-transporting P-type ATPase. Conclusion We identified a novel deletion variant in a Wilson disease patient harboring compound heterozygous variants in ATP7B. This finding expands the known spectrum of pathogenic ATP7B variants.
The molecular and functional spectrum of SLC25A4-associated disease is expanded and may inform clinical practice, including genetic interventions such as preimplantation genetic diagnosis, premarital genetic screening, targeted genetic counseling, and cascade testing of at-risk family members.
Mazhor Aldosary, Hanan Alqudairy, Nourah Alshalan et al.· International Journal of Mol...· 0 citations
There is moderate evidence that the two identified HARS1 variants are responsible for the recessive phenotype, suggesting that the allelic and clinical heterogeneity of HARS1‐related disease is expanded.
Christina Del Greco, Allison R. Cale, Karl Haeberlein et al.· Journal of the peripheral ne...· 0 citations
A Chinese pediatric patient with epilepsy and congenital heart disease who carries a novel CACNA1E variant that lies in a highly conserved and intolerant region provides a potential treatment clue for ACTH responsiveness in CACNA1E-related spasms.
Juan Pan, Mei-Fang Zhao, Zhaochuan Liu et al.· Frontiers in Medicine· 0 citations
ABSTRACT Wilson disease (WD) is a rare disorder that may be missed because of atypical presentations. We present a 47-year-old asymptomatic man who was incidentally discovered to have hepatic steatosis and cirrhosis without features of the metabolic syndrome and with normal physical examination and liver function tests. Very low ceruloplasmin and high urine copper prompted evaluation for WD. He had no Kayser–Fleischer rings. Genetic testing revealed a novel homozygous splice-site ATP7B variant (NM_000053.2:c.1707+2dupT p.(?)), the first reported case of homozygosity for this mutation. This case highlights the importance of considering WD in patients with unexplained hepatic steatosis and cryptogenic cirrhosis.
Ouwais Alkhateb, Don C. Rockey, K. Barada· ACG Case Reports Journal· 0 citations
Unlike previously reported KIF1C-related cases, this cohort exhibits a later onset, rare pyramidal involvement, and no consistent neuroimaging abnormalities, thereby expanding the known clinical spectrum of KIF1C-associated disease.
Catarina Borges, Sara Lima, Mafalda Perdicoulis et al.· Current Genetic Medicine Rep...· 0 citations
Background
. Hereditary Tyrosinemia Type 1 (HT1) is an orphan disease belonging to the group of amino acid metabolism disorders, with an autosomal recessive pattern of inheritance. It is caused by a mutation in the FAH gene, which encodes the enzyme fumarylacetoacetate hydrolase. The clinical presentation is polymorphic. Diagnosis is based on the detection of specific metabolites in biological samples and molecular genetic testing. Early diagnosis determines the effectiveness of therapy and the prognosis of the disease.
Clinical case description
. We present a clinical case of early detection of HT1 in a female newborn through expanded neonatal screening. The clinical picture was characterized by hepatomegaly, coagulopathy, and specific biomarkers, including elevated levels of succinylacetone in the blood. This finding served as the basis for immediate initiation of nitisinone therapy and an individually calculated low protein diet supplemented with a specialized amino acid mixture. Molecular genetic testing confirmed the diagnosis: a previously described pathogenic nucleotide sequence variant, chr15:80181069G>C in the FAH gene in a homo/hemizygous state, was identified. This variant leads to a missense substitution c.1090G>C, p.(Glu364Gln). During the follow up period, the patient has shown a favorable course of the disease.
Conclusion
. Early diagnosis of HT1 based on specific succinylacetone screening and timely initiation of pathogenetic therapy combined with dietary management ensure a favorable prognosis for the disease.
T. A. Astakhova, T. Bairova, A. V. Belskikh et al.· Acta Biomedica Scientia· 0 citations
