Copper-histidine therapy in an infant with novel splice-site variant in the<i>ATP7A</i>gene of Menkes disease: the first experience in South East Asia and literature review

Panichsillaphakit, Ekkarit; Kwanbunbumpen, Tanisa; Chomtho, Sirinuch; Visuthranukul, Chonnikant

doi:10.1136/bcr-2021-247937

Cited by 4 publications

(4 citation statements)

References 33 publications

(60 reference statements)

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“…On the other hand, the ATP7A gene is expressed more in horned cultivars than in hornless breeds, which further proves that ATP7A genes may affect the formation and even size of horns. We found that the ATP7A gene is specifically highly expressed in soft horns and skin tissues, but almost not expressed in other internal organs, combined with previous studies ( Panichsillaphakit et al, 2022 ), indicating that the ATP7A gene is closely related to the function of the skin, may play a role in the keratinization of the skin, and participate in the formation process of horn sheaths. In four animals, humans, cattle, pigs and sheep, the ATP7A gene is only highly expressed in the skin of horned animals, sheep.…”

Section: Discussionsupporting

confidence: 84%

Genetic diversity, tissue-specific expression, and functional analysis of the ATP7A gene in sheep

Li,

Du,

et al. 2023

Front. Genet.

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In humans, variation of the ATP7A gene may cause cranial exostosis, which is similar to “human horn,” but the function of the ATP7A gene in sheep is still unknown. Tissue expression patterns and potential functional loci analysis of the ATP7A gene could help understand its function in sheep horn. In this study, we first identified tissue, sex, breed, and species-specific expression of the ATP7A gene in sheep based on the RNA-sequencing (RNA-seq) data. Second, the potential functional sites of the ATP7A gene were analyzed by using the whole genome sequencing (WGS) data of 99 sheep from 10 breeds. Last, the allele-specific expression of the ATP7A gene was explored. Our result showed the ATP7A gene has significantly higher expression in the big horn than in the small horn, and the ATP7A gene has high expression in the horn and skin, suggesting that this gene may be related to the horn. The PCA results show that the region around the ATP7A can distinguish horned and hornless groups to some extent, further indicating that the ATP7A may be related to horns. When compared with other species, we find seven ruminate specific amino acid sites of the ATP7A protein, which can be important to the ruminate horn. By analyzing WGS, we found 6 SNP sites with significant differences in frequency in horned and hornless populations, and most of these variants are present in the intron. But we still find some potential functional sites, including three missenses, three synonymous mutations, and four Indels. Finally, by combining the RNA-seq and WGS functional loci results, we find three mutations that showed allele-specific expression between big and small horns. This study shows that the ATP7A gene in sheep may be related to horn size, and several potential functional sites we identified here can be useful molecular markers for sheep horn breeding.

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Section: Discussionsupporting

confidence: 84%

Genetic diversity, tissue-specific expression, and functional analysis of the ATP7A gene in sheep

Li,

Du,

et al. 2023

Front. Genet.

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“…Early detection is hindered by the lack of newborn screening and overlap with other disorders. Mutations in the ATP7A gene lead to copper deficiency, affecting the nervous system [2,4].…”

Section: Discussionmentioning

confidence: 99%

“…The primary treatments for MD patients are copper injections or oral supplements, which, if begun early, may improve the patient's prognosis and quality of life. Nonetheless, the majority of MD patients pass away before turning three years old, and the prognosis is typically dismal [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Menkes disease: An update

Gowder

2023

AJBSR

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“…Опублікований досвід на цю тему показує, що парентеральне введення міді в будь-якій формі відновлює циркулюючу мідь і церулоплазмін до референтних рівнів, на відміну від перорального прийому міді. Разом із тим, хоча низькі запаси міді в печінці швидко поповнюються за допомогою парентеральної терапії, вміст міді в мозку під час лікування збільшується лише поступово, якщо взагалі зростає [41].…”

Section: вступunclassified

Menkes Disease: A Literature Review and Clinical Case

Tokarchuk,

Chekotun,

Starynets

et al. 2024

Neonatol. hìr. perinat. med.

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Menkes Kinky Hair Disease (MKHD) is characterized by an abnormality in copper metabolism caused by a mutation in the ATP7A gene, which is located on Xq13.3 and has 23 exons. In addition, this gene encodes 1500 amino acids and is expressed in large quantities in various organs. It’s worth mentioning that about 357 diff erent mutations have been identifi ed in the ATP7A gene. It is a relatively rare disease with an incidence of 1 case per 100,000 to 250,000 live births. MKHD is an X-linked recessive trait that almost exclusively aff ects boys.The diagnosis of this rare disease is based on the genetic- molecular study of a metabolic disease panel, including the ATP7A gene and the biochemical phenotype (a decrease in serum copper and ceruloplasmin levels).In developing therapeutic strategies for individuals with Menkes disease, three fundamental problems are being addressed: 1) unlocking the absorption of copper in the intestine; 2) making copper available to enzymes in cells that require it as a cofactor; and 3) identifying infants with Menkes disease and initiating treatment at a very early stage of life, before irreversible neurodegeneration occurs. This article presents a clinical case of Menkes disease in a 7-month-old boy. The diagnosis was confi rmed by molecular genetic testing (NGS) of the Neurometabolic Disorders Panel, which included the ATP7A gene and biochemical phenotype. The described case illustrates the complexity of diagnosing Menkes disease in the neonatal period due to the non-specifi city of disease symptoms (lethargy, weak sucking, weight loss, etc.) and the importance of biochemical and molecular genetic methods of fetal investigation in subsequent pregnancies or in a newborn sibling for early diagnosis and treatment. This case will be published with the consent of the mother in accordance with bioethical principles.

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Copper-histidine therapy in an infant with novel splice-site variant in theATP7Agene of Menkes disease: the first experience in South East Asia and literature review

Cited by 4 publications

References 33 publications

Genetic diversity, tissue-specific expression, and functional analysis of the ATP7A gene in sheep

Genetic diversity, tissue-specific expression, and functional analysis of the ATP7A gene in sheep

Menkes disease: An update

Menkes Disease: A Literature Review and Clinical Case

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