Severe congenital neutropenia due to G6PC3 deficiency: Case series of five patients and literature review

Vélez-Tirado, Natalia; Yamazaki‐Nakashimada, Marco Antonio; Valentín, Enrique López; Partida-Gaytán, Armando; Scheffler‐Mendoza, Selma; Semerena, Genny M Chaia; Álvarez-Cardona, Aristóteles; Suárez-Gutiérrez, Marcos; Torres, Edgar Alejandro Medina; Capetillo, Patricia Baeza; Hirschmugl, Tatjana; Garncarz, Wojciech; Espinosa‐Padilla, Sara Elva; Hernández, Jesús Aguirre; Klein, Christoph; Boztuğ, Kaan; Reyes, Saúl Oswaldo Lugo

doi:10.1111/sji.13136

Cited by 7 publications

(12 citation statements)

References 23 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, this novel mutation has been observed in only five patients, including the two cases presented in this study, all hailing from the southern region of Saudi Arabia. With the inclusion of our two cases, the published cases of Dursun syndrome in Saudi Arabia have now reached 10, contributing to the overall count of 94 cases reported worldwide 4,5 …”

Section: Introductionmentioning

confidence: 87%

“…Globally, 92 cases of Dursun Syndrome have been reported in the literature, with eight of these cases originating from Saudi Arabia 4,5 . A specific genetic variant (c.479C>T; Ser160Leu) in the G6PC3 gene has been identified as the causative mutation in these cases, leading to a substitution of serine to leucine at position 160.…”

Section: Introductionmentioning

confidence: 99%

“…With the inclusion of our two cases, the published cases of Dursun syndrome in Saudi Arabia have now reached 10, contributing to the overall count of 94 cases reported worldwide. 4,5 As our understanding of these syndromes deepens, it becomes crucial to recognize the increasing prevalence of congenital neutropenia globally. This growing incidence emphasizes the significance of closely monitoring patients with neutropenia, enabling early detection of potential complications and timely intervention.…”

Section: Introductionmentioning

confidence: 99%

“…Globally, 92 cases of Dursun Syndrome have been reported in the literature, with eight of these cases originating from Saudi Arabia. 4 , 5 A specific genetic variant (c.479C>T; Ser160Leu) in the G6PC3 gene has been identified as the causative mutation in these cases, leading to a substitution of serine to leucine at position 160. Interestingly, this novel mutation has been observed in only five patients, including the two cases presented in this study, all hailing from the southern region of Saudi Arabia.…”

Section: Introductionmentioning

confidence: 99%

“…With the inclusion of our two cases, the published cases of Dursun syndrome in Saudi Arabia have now reached 10, contributing to the overall count of 94 cases reported worldwide. 4 , 5 …”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Case report of congenital neutropenia type 4 with glucose‐6‐phosphatase catalytic subunit 3 (G6PC3) deficiency

Dhayhi,

Mahnashi,

Mokhasha

et al. 2024

Clinical Case Reports

View full text Add to dashboard Cite

Key Clinical MessageCongenital neutropenia syndromes encompass a group of genetic disorders characterized by persistent neutropenia and recurrent infections inherited in an autosomal recessive, dominant, or X‐linked manner. These syndromes arise from mutations in various genes, and one of the significant genes involved is glucose‐6‐phosphatase catalytic subunit 3 (G6PC3), giving rise to a condition known as Dursun syndrome. As per existing knowledge, a total of 92 cases of Dursun syndrome have been reported globally, including eight cases from Saudi Arabia. Our study identified two additional cases exhibiting neutropenia since the early postnatal period and recurrent admissions due to infections. Additionally, these patients presented with oral ulcers, chronic diarrhea, and anomalies affecting the cardiac and genitourinary systems. The rising incidence of congenital neutropenia on a global scale necessitates heightened vigilance among clinicians to ensure thorough follow‐up of patients with neutropenia. This proactive approach can lead to early detection and appropriate management of associated complications, ultimately improving patient outcomes.

show abstract

Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…With the inclusion of our two cases, the published cases of Dursun syndrome in Saudi Arabia have now reached 10, contributing to the overall count of 94 cases reported worldwide. 4 , 5 …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Case report of congenital neutropenia type 4 with glucose‐6‐phosphatase catalytic subunit 3 (G6PC3) deficiency

Dhayhi,

Mahnashi,

Mokhasha

et al. 2024

Clinical Case Reports

View full text Add to dashboard Cite

show abstract

Severe congenital neutropenia type 4 with early-onset inflammatory bowel disease attributed to a G6PC3 variant (not previously associated with disease): A case report and a literature review

et al. 2023

View full text Add to dashboard Cite

Molecular and clinical characterization of a founder mutation causing G6PC3 deficiency

Zhen,

Betti,

Kars

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Background: G6PC3 deficiency is a rare genetic disorder that causes syndromic congenital neutropenia. It is driven by the intracellular accumulation of a metabolite named 1,5-anhydroglucitol-6-phosphate (1,5-AG6P) that inhibits glycolysis. Patients display heterogeneous extra-hematological manifestations, contributing to delayed diagnosis. Objective: The G6PC3 c.210delC variant has been identified in patients of Mexican origin. We set out to study the origin and functional consequence of this mutation. Furthermore, we sought to characterize the clinical phenotypes caused by it. Methods: Using whole-genome sequencing data, we conducted haplotype analysis to estimate the age of this allele and traced its ancestral origin. We examined how this mutation affected G6PC3 protein expression and performed extracellular flux assays on patient-derived cells to characterize how this mutation impacts glycolysis. Finally, we compared the clinical presentations of patients with the c.210delC mutation relative to other G6PC3 deficient patients published to date. Results: Based on the length of haplotypes shared amongst ten carriers of the G6PC3 c.210delC mutation, we estimated that this variant originated in a common ancestor of indigenous American origin. The mutation causes a frameshift that introduces a premature stop codon, leading to a complete loss of G6PC3 protein expression. When treated with 1,5-anhydroglucitol (1,5-AG), the precursor to 1,5-AG6P, patient-derived cells exhibited markedly reduced engagement of glycolysis. Clinically, c.210delC carriers display all the clinical features of syndromic severe congenital neutropenia type 4 observed in prior reports of G6PC3 deficiency. Conclusion: The G6PC3 c.210delC is a loss-of-function mutation that arose from a founder effect in the indigenous Mexican population. These findings may facilitate the diagnosis of additional patients in this geographical area. Moreover, the in vitro 1,5-AG-dependent functional assay used in our study could be employed to assess the pathogenicity of additional G6PC3 variants.

show abstract

Severe congenital neutropenia due to G6PC3 deficiency: Case series of five patients and literature review

Cited by 7 publications

References 23 publications

Case report of congenital neutropenia type 4 with glucose‐6‐phosphatase catalytic subunit 3 (G6PC3) deficiency

Case report of congenital neutropenia type 4 with glucose‐6‐phosphatase catalytic subunit 3 (G6PC3) deficiency

Severe congenital neutropenia type 4 with early-onset inflammatory bowel disease attributed to a G6PC3 variant (not previously associated with disease): A case report and a literature review

Molecular and clinical characterization of a founder mutation causing G6PC3 deficiency

Contact Info

Product

Resources

About