<i>GALE</i>
            variants associated with syndromic manifestations, macrothrombocytopenia, bleeding, and platelet dysfunction

Marín-Quílez, Ana; Buduo, Christian A. Di; Benito, Rocí­o; Balduini, Alessandra; Rivera, José; Bastida, José María

doi:10.1080/09537104.2023.2176699

Cited by 3 publications

(3 citation statements)

References 21 publications

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“…Although we cannot exclude that possible genomic changes (such as intronic or complex structural variants), not detected by our WES study, could be involved in this phenotype and considering that cardiac defects have been previously reported in other ACTN1-RT individuals, 7 we speculate that some ACTN1 variants, especially when present in the homozygous state, could at least contribute to these cardiac abnormalities, possibly together with other genetic players. Of note, several different forms of genetic thrombocytopenia associated with cardiac defects have been previously described, 2,[16][17][18] an aspect that would require an adequate differential diagnosis for patients who present with these features.…”

Section: Discussionmentioning

confidence: 99%

ACTN1‐related thrombocytopenia: Homozygosity for an ACTN1 variant results in a more severe phenotype

Zanchetta,

Barozzi,

Isidori

et al. 2024

Br J Haematol

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SummaryACTN1‐related thrombocytopenia is a rare disorder caused by heterozygous variants in the ACTN1 gene characterized by macrothrombocytopenia and mild bleeding tendency. We describe for the first time two patients affected with ACTN1‐RT caused by a homozygous variant in ACTN1 (c.982G>A) with mild heart valve defects unexplained by any other genetic variants investigated by WES. Within the reported family, the homozygous sisters have moderate thrombocytopenia and marked platelet macrocytosis with giant platelets, revealing a more severe haematological phenotype compared to their heterozygous relatives and highlighting a significant effect of allelic burden on platelet size. Moreover, we hypothesize that some ACTN1 variants, especially when present in the homozygous state, may also contribute to the cardiac abnormalities.

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Section: Discussionmentioning

confidence: 99%

ACTN1‐related thrombocytopenia: Homozygosity for an ACTN1 variant results in a more severe phenotype

Zanchetta,

Barozzi,

Isidori

et al. 2024

Br J Haematol

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“…It has many clinical symptoms in infants, including hypotonia, poor feeding, vomiting, hepatomegaly, and cataracts. Diagnosis is made by measuring GALE activity in RBCs [ 83 , 84 ].…”

Section: Thrombocytopeniamentioning

confidence: 99%

Blood cytopenias as manifestations of inherited metabolic diseases: a narrative review

Moutapam-Ngamby—Adriaansen,

Maillot,

Labarthe

et al. 2024

Orphanet J Rare Dis

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Inherited Metabolic Diseases (IMD) encompass a diverse group of rare genetic conditions that, despite their individual rarity, collectively affect a substantial proportion, estimated at as much as 1 in 784 live births. Among their wide-ranging clinical manifestations, cytopenia stands out as a prominent feature. Consequently, IMD should be considered a potential diagnosis when evaluating patients presenting with cytopenia. However, it is essential to note that the existing scientific literature pertaining to the link between IMD and cytopenia is limited, primarily comprising case reports and case series. This paucity of data may contribute to the inadequate recognition of the association between IMD and cytopenia, potentially leading to underdiagnosis. In this review, we synthesize our findings from a literature analysis along with our clinical expertise to offer a comprehensive insight into the clinical presentation of IMD cases associated with cytopenia. Furthermore, we introduce a structured diagnostic approach underpinned by decision-making algorithms, with the aim of enhancing the early identification and management of IMD-related cytopenia.

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“…Notwithstanding, the nature and severity of symptoms in epimerase deficiency remain unclear, as do the mechanisms by which some variants are associated with severe syndromic disorders that include hematological manifestations, while others are not [ 56 ]. Extending the analysis to additional receptors or other crucial glycoproteins may open new avenues toward understanding the impact of glycosylation on megakaryopoiesis.…”

Section: Disorders Of Glycosylation Associate With Syndromic Thromboc...mentioning

confidence: 99%

Inherited Thrombocytopenia Caused by Variants in Crucial Genes for Glycosylation

Marín-Quílez

Díaz-Ajenjo

Buduo

et al. 2023

IJMS

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Protein glycosylation, including sialylation, involves complex and frequent post-translational modifications, which play a critical role in different biological processes. The conjugation of carbohydrate residues to specific molecules and receptors is critical for normal hematopoiesis, as it favors the proliferation and clearance of hematopoietic precursors. Through this mechanism, the circulating platelet count is controlled by the appropriate platelet production by megakaryocytes, and the kinetics of platelet clearance. Platelets have a half-life in blood ranging from 8 to 11 days, after which they lose the final sialic acid and are recognized by receptors in the liver and eliminated from the bloodstream. This favors the transduction of thrombopoietin, which induces megakaryopoiesis to produce new platelets. More than two hundred enzymes are responsible for proper glycosylation and sialylation. In recent years, novel disorders of glycosylation caused by molecular variants in multiple genes have been described. The phenotype of the patients with genetic alterations in GNE, SLC35A1, GALE and B4GALT is consistent with syndromic manifestations, severe inherited thrombocytopenia, and hemorrhagic complications.

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GALE variants associated with syndromic manifestations, macrothrombocytopenia, bleeding, and platelet dysfunction

Cited by 3 publications

References 21 publications

ACTN1‐related thrombocytopenia: Homozygosity for an ACTN1 variant results in a more severe phenotype

ACTN1‐related thrombocytopenia: Homozygosity for an ACTN1 variant results in a more severe phenotype

Blood cytopenias as manifestations of inherited metabolic diseases: a narrative review

Inherited Thrombocytopenia Caused by Variants in Crucial Genes for Glycosylation

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