A Novel G6PC3 Gene Mutation in a Patient With Severe Congenital Neutropenia

Aytekin, Caner; Germeshausen, Manuela; Tuygun, Nilden; Doğu, Figen; İkincioğulları, Aydan

doi:10.1097/mph.0b013e3182679000

Cited by 13 publications

(17 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, ER stress was normal, and increased apoptosis was not evident. Similar findings were previously described in other patients with G6PC3 deficiency (15). The reason underlying the variability of bone marrow phenotype and ER stress-induced apoptosis is unclear.…”

Section: Discussionsupporting

confidence: 87%

Testicular failure in a patient with G6PC3 deficiency

et al. 2014

View full text Add to dashboard Cite

Background: Glucose-6-phosphatase-β (G6PC3) deficiency is characterized by congenital neutropenia and variable developmental disorders, including those of the cardiovascular system and the urogenital system (e.g., cryptorchidism) and a peculiar visibility of subcutaneous veins. Methods: A patient with clinical findings suggestive of G6PC3 deficiency was investigated. Genetic, hematopathologic, immunologic, and endocrine work-up were performed. results: The reported patient had binucleotide deletion mutation in G6PC3 and displayed the full spectrum of clinical manifestations associated with G6PC3 deficiency including neutropenia. The reported patient had normal bone marrow cellularity without increased apoptosis, and his neutrophils displayed normal respiratory burst activity. Endocrine workup revealed low testosterone levels, which did not respond to human chorionic gonadotropin stimulation, extremely elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, and undetectable anti-Müllerian hormone, all of which are suggestive of testicular failure or anorchia. conclusion: Our report extends the knowledge about this syndrome and suggests a role for G6PC3 in testicular differentiation and formation. Urogenital dysmorphism could indeed be unrelated to G6PC3 and secondary to consanguinity. However, given the similar description of urogenital anomalies in previous reports of this syndrome, the dysmorphism in our patient is likely related.

show abstract

Section: Discussionsupporting

confidence: 87%

Testicular failure in a patient with G6PC3 deficiency

et al. 2014

View full text Add to dashboard Cite

show abstract

“…These include growth hormone deficiency in two patients, including one with an enlarged anterior pituitary lobe [11]. Delayed puberty, hypogonadotropic hypogonadism or poorly developed secondary sexual characteristics have been noted in six patients [10,11,26,27]. Additionally, hypothyroidism was noted in an affected brother and sister [10].…”

Section: Introductionmentioning

confidence: 99%

“…In the same family one child had raised gamma-glutamyl transferase, liver calcifications and choledocholithiasis and one adult patient had a low HDL levels and increased amylase activity. Raised serum cholesterol and LDL levels were recently noted in one patient [27]. …”

Section: Introductionmentioning

confidence: 99%

“…Of note, the c.416G > T mutation has been identified in two patients and predicted to be a missense change (p.S139I) [11,27]. However, the codon for residue S139 is determined by the last two nucleotides of exon 3 and the first nucleotide of exon 4.…”

Section: Introductionmentioning

confidence: 99%

“…Biochemical profile monitoring could be part of routine part of the follow-up. Of note, raised total serum cholesterol and LDL levels were reported to normalize with statins in one patient [27]. Rare manifestations such as PHT and IBD should be managed according to standard guidelines.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A clinical and molecular review of ubiquitous glucose-6-phosphatase deficiency caused by G6PC3 mutations

Banka

Newman

2013

Orphanet J Rare Dis

View full text Add to dashboard Cite

The G6PC3 gene encodes the ubiquitously expressed glucose-6-phosphatase enzyme (G-6-Pase β or G-6-Pase 3 or G6PC3). Bi-allelic G6PC3 mutations cause a multi-system autosomal recessive disorder of G6PC3 deficiency (also called severe congenital neutropenia type 4, MIM 612541). To date, at least 57 patients with G6PC3 deficiency have been described in the literature.G6PC3 deficiency is characterized by severe congenital neutropenia, recurrent bacterial infections, intermittent thrombocytopenia in many patients, a prominent superficial venous pattern and a high incidence of congenital cardiac defects and uro-genital anomalies. The phenotypic spectrum of the condition is wide and includes rare manifestations such as maturation arrest of the myeloid lineage, a normocellular bone marrow, myelokathexis, lymphopaenia, thymic hypoplasia, inflammatory bowel disease, primary pulmonary hypertension, endocrine abnormalities, growth retardation, minor facial dysmorphism, skeletal and integument anomalies amongst others. Dursun syndrome is part of this extended spectrum. G6PC3 deficiency can also result in isolated non-syndromic severe neutropenia. G6PC3 mutations in result in reduced enzyme activity, endoplasmic reticulum stress response, increased rates of apoptosis of affected cells and dysfunction of neutrophil activity.In this review we demonstrate that loss of function in missense G6PC3 mutations likely results from decreased enzyme stability. The condition can be diagnosed by sequencing the G6PC3 gene. A number of G6PC3 founder mutations are known in various populations and a possible genotype-phenotype relationship also exists. G6PC3 deficiency should be considered as part of the differential diagnoses in any patient with unexplained congenital neutropenia.Treatment with G-CSF leads to improvement in neutrophil numbers, prevents infections and improves quality of life. Mildly affected patients can be managed with prophylactic antibiotics. Untreated G6PC3 deficiency can be fatal. Echocardiogram, renal and pelvic ultrasound scans should be performed in all cases of suspected or confirmed G6PC3 deficiency. Routine assessment should include biochemical profile, growth profile and monitoring for development of varicose veins or venous ulcers.

show abstract

CDG and immune response: From bedside to bench and back

Pascoal

Francisco

Ferro

et al. 2019

J of Inher Metab Disea

View full text Add to dashboard Cite

Glycosylation is an essential biological process that adds structural and functional diversity to cells and molecules, participating in physiological processes such as immunity. The immune response is driven and modulated by protein‐attached glycans that mediate cell‐cell interactions, pathogen recognition and cell activation. Therefore, abnormal glycosylation can be associated with deranged immune responses. Within human diseases presenting immunological defects are congenital disorders of glycosylation (CDG), a family of around 130 rare and complex genetic diseases. In this review, we have identified 23 CDG with immunological involvement, characterized by an increased propensity to—often life‐threatening—infection. Inflammatory and autoimmune complications were found in 7 CDG types. CDG natural history(ies) and the mechanisms behind the immunological anomalies are still poorly understood. However, in some cases, alterations in pathogen recognition and intracellular signaling (eg, TGF‐β1, NFAT, and NF‐κB) have been suggested. Targeted therapies to restore immune defects are only available for PGM3‐CDG and SLC35C1‐CDG. Fostering research on glycoimmunology may elucidate the involved pathophysiological mechanisms and open new therapeutic avenues, thus improving CDG patients' quality of life.

show abstract

A Novel G6PC3 Gene Mutation in a Patient With Severe Congenital Neutropenia

Cited by 13 publications

References 19 publications

Testicular failure in a patient with G6PC3 deficiency

Testicular failure in a patient with G6PC3 deficiency

A clinical and molecular review of ubiquitous glucose-6-phosphatase deficiency caused by G6PC3 mutations

CDG and immune response: From bedside to bench and back

Contact Info

Product

Resources

About