Table 1 Patients with homozygous missense G6PC3 mutation
Fam | Pt. no. | Eth | Sex | Age | Mutation | Protein | Atypical hematological features | Bone marrow | Vascular features | Cardiac features | Renal and genital defects | Other features | Ref |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 1 | Pak | F | 10 | c.[130C > T]; [130C > T] | p.[P44S]; [P44S] | None | Normal cellularity and neutrophil maturation. | None | None | None | None | |
2 | 2 | Pak | M | 20 | c.[130C > T]; [130C > T] | p.[P44S]; [P44S] | None | Normocellular with mild left-sided shift. | None | None | None | A single episode of myositis | |
3 | 3 | Pak | M | 10 | c.[130C > T]; [130C > T] | p.[P44S]; [P44S] | None | Normocellular | None | None | None | None | [14] |
4 | 4 | Turk | M | 18 m | c.[346A > G]; [346A > G] | p.[M116V]; [M116V] | T-cell lymphopenia, monocytosis and anemia. | Dysplastic | Primary PHT since infancy. | ASD | Bilateral inguinal herniae and undescended testes | Diagnosed with Dursun syndrome. Thymus hypoplasia, proximally placed thumbs, broad nasal bridge, pectus carinatum and high arched palate. Died at 18 m due to severe respiratory distress. | |
5 | Turk | F | 18Â m | Lymphopenia, monocytosis and anemia. | Dysplastic | Primary PHT since infancy. | ASD | None | Diagnosed with Dursun syndrome. Thymus hypoplasia, proximally placed thumbs, broad nasal bridge, pectus carinatum, single palmar creases and high arched palate. Died at 18Â m due to severe respiratory distress. | ||||
5 | 6 | NA | NA | NA | c.[347 T > A]; [347 T > A] | p.[M116K]; [M116K] | None | Not described | Prominent veins | ASD, mild mitral and tricuspid insufficiency | None | Learning difficulties and Hypogonadotrophic hypogonadism. | [26] |
6 | 7 | Pak | F | 13 | c.[347 T > C]; [347 T > C] | p.[M116T]; [M116T] | None | Normal cellularity and neutrophil maturation. | None | None | None | None | |
7 | 8 | NA | F | NA | c.[353C > G]; [c.353C > G]* | p.[T118R]; [T118R] | None | Not described | Not described | ASD | Not described | Not described | [17] |
8 | 9 | Turk* | F | 13 | c.[461 T > C]; [461 T > C]* | p.[L154P]; [L154P] | None | Hypercellular marrow, myeloid hyperplasia, no maturation arrest. | Prominent veins on neck, chest, and abdomen. | Mild mitral regurgitation | None | Frontal bossing, depressed nasal bridge, upturned nose and retrognathia. Learning difficulties. Poorly developed secondary sexual characteristics. Elevated serum total cholesterol and LDL cholesterol. | [27] |
9 | 10 | Turk | F | 12 | c.[554 T > C]; [554 T > C] | p.[L185P]; [L185P] | None | Not described | Prominent veins | ASD and pulmonary valve stenosis. | None | None | [9] |
10 | 11 | Turk | F |  | c.[623 T > G]; [623 T > G] | p.[L208R]; [L208R] | None | Not described | None | PFO and tricuspid insufficiency. | None | None | [14] |
11 | 12 | Arab | F | 12 | c.[758G > A]; [758G > A] | p.[R253H]; [p.R253H] | None | Reduced mature neutrophils. | Prominent veins | ASD and small PDA. | Right grade III VUR. Discontinuous labia majora and minora. | Close set, down sloping eyes, low set ears | [11] |
12 | 13 | Arm, Turk | M | 6 | c.[758G > A]; [758G > A] | p.[R253H]; [p.R253H] | None | Reduced mature neutrophils. | Prominent veins | ASD | Bilateral cryptorchidism | None | [9] |
14 | Arm, Turk | F | 3 | None | Reduced mature neutrophils. | Prominent veins and pulmonary venous anomaly. | Cor triatriatum | None | None | [9] | |||
15 | Arm, Turk | F | 11 | None | Not described | Prominent veins | ASD and mitral insufficiency. | None | None | [9] | |||
16 | Arm, Turk | M | 6 | None | Reduced mature neutrophils. | Prominent veins | ASD | Bilateral cryptorchidism | None | ||||
13 | 17 | Arm, Turk | M | 4 | c.[758G > A]; [758G > A] | p.[R253H]; [p.R253H] | None | Reduced mature neutrophils. | Prominent veins | Not reported | Not reported | Poor growth | [9] |
14 | 18 | Arab, Israel | F | 29 | c.[758G > A]; [758G > A] | p.[R253H]; [p.R253H] | None | Hypercellular marrow with myeloid hyperplasia. Increased blast-like forms and megakaryocytes including atypical forms. | Prominent veins and varicose veins. | None | None | SGA, mild learning difficulties. Hypothyroidism. Dyslipidemia and elevated pancreatic amylase and uric acid. | [10] |
19 | Arab, Israel | M | 26 | None | Mildly decreased myeloid cells. Increased megakaryocytes. | Prominent veins and varicosities. | None | None | SGA, FTT and mild learning difficulties. Hypothyroidism and secondary sexual characteristics. | [10] | |||
20 | Arab, Israel | F | 25 | None | Hypercellular marrow. Mild dysmyelopoetic changes. Decreased erythropoiesis. | Prominent veins and varicosities. | ASD and PDA | None | Poor growth, mild learning difficulties and delayed menarche. | [10] | |||
21 | Arab, Israel | M | 2 | Monocytosis, lymphopenia. | Normocellular | Prominent veins on face. PHT. | ASD, PDA and critical PS. | Bilateral crytorchidism | Liver calcifications. Mild learning difficulties. Pectus excavatum. Raised gamma glutamyltranspeptidases. | [10] | |||
15 | 22 | Cauc | M | 9 | c.[778G > C]; [778G > C] | p.[G260R]; [G260R] | None | Not described | Prominent veins | ASD | Micropenis | Mild developmental delay. Hypoplastic nipples, malar flattening, bilateral metatarsus adductus and thick erythematous skin on palms and soles. | [11] |
16 | 23 | Cauc | M | 11 | c.[778G > C]; [778G > C] | p.[G260R]; [G260R] | None | Reduced mature neutrophils. | Prominent veins | PDA, ASD, bicuspid aortic valve. | Cryptorchidism andmicropenis | Mild developmental delay. Clubbing. Palmar erythema, inverted nipples and malar flattening. | [11] |
17 | 24 | White Ger | F | 7 | c.[778G > C]; [778G > C] | p.[G260R]; [G260R] | None | Not described | Prominent veins | ASD | Urachal fistula | Microcephaly | [9] |
18 | 25 | White Ger | M | 17 | c.[778G > C]; [778G > C] | p.[G260R]; [G260R] | None | Not described | Prominent veins | ASD | Bilateral cryptorchidism and genital dysplasia | Growth retardation | [9] |
19 | 26 | NA | M | NA | c.[778G > C]; [778G > C] | p.[G260R]; [G260R] | None | Not described | Prominent veins | ASD | Bilateral cryptorchidism and genital dysplasia | Hypogammaglobunemia, microcephaly | [26] |
20 | 27 | Cauc | M | 13 | c.[778G > C]; [778G > C] | p.[G260R]; [G260R] | Iron deficiency anaemia | Pyknotic neutrophils, no maturation arrest. Myelokathexis. Emperipolesis of neutrophils in 12% of megakaryocytes. Atypical mononuclear megakaryocytes | Prominent veins. Mild PHT. | PFO, thickened mitral valve and dilated right ventricle. | Bilateral cryptorchidism, unilateral testicular agenesis, testicular microlithiasis and inguinal hernia. | Poor growth, microcephaly. Buffalo hump, ligamentous laxity, mild proximal muscle weakness and mild sensorineural hearing loss. | [20] |
28 | Cauc | F | 9 | Iron deficiency anaemia | Pyknotic Neutrophils, no maturation arrest. Myelokathexis. Emperipolesis of neutrophils in 12% of megakaryocytes. Atypical mononuclear megakaryocytes | Prominent veins | Large ASD | None | Poor growth, microcephaly, ligamentous laxity, mild proximal muscle weakness and mild sensorineural hearing loss. | [20] | |||
21 | 29 | Turk | M | ? | c.[779G > A]; [779G > A] | p.[G260D]; [G260D] | None | Maturation arrest at myelocyte/promyelocyte stage | Prominent veins | ASD | Left grade II hydronephrosis | Triangular face, frontal bossing, micrognathia and depressed nasal bridge. Cutis laxa. Bilateral hearing loss. Growth retardation. | [11] |