Information on SCN11

Name: Severe congenital neutropenia 11 | Acronym: SCN11
Alt. names: Congenital neutropenia, severe, 11

Gene: SEC61A1 | MOI: Autosomal dominant | Mechanism of action: Haploinsufficiency

No. of cases in DB: 1 | First reported in: 2020

Last updated on: 2023-05-26 by Xiao P. Peng

OMIM: 620674

Orphanet: -

MONDO: -

DOID: -

ClinGen:

Description

Thus far, one patient has been reported with a heterozygous SEC61A1 mutation leading to severe congenital neutropenia without hypogammaglobulinemia or nephropathy (PMID: 32325141) - a 19-year-old European female diagnosed with SCN at age 2 years old with a history of recurrent sinopulmonary, GI and skin infections, as well as oral ulcers, defective wound healing, gingivitis, and an episode of limited verrucae plantaris. Immunophenotyping prior to initiation of daily G-CSF was also notable for hypergammaglobulinemia, mild thrombocytopenia, and discrete intermittent anemia. Bone marrow analysis before G-CSF treatment showed granulopoietic maturation arrest at the promyelocyte and myelocyte level, thought to be a consequence of dysregulated unfolded protein response, increased susceptibility to ER stress and greater tendency to apoptosis.

Management

Interestingly, although the patient was clinically responsive to G-CSF, her circulating neutrophils remained immature with evidence of nuclear hypo-segmentation.

Summary of clinical findings

[Considering only Definitive and Possible cases]

Rank	Clinical phenotype	Present	Absent
1	Abnormality of the gingiva	1 (99.9%)	0 (0.0%)
2	Abscess	1 (99.9%)	0 (0.0%)
3	Dermatitis	1 (99.9%)	0 (0.0%)
4	Abnormal paranasal sinus morphology	1 (99.9%)	0 (0.0%)
5	Sinusitis	1 (99.9%)	0 (0.0%)
6	Otitis media	1 (99.9%)	0 (0.0%)
7	Abnormality of the middle ear	1 (99.9%)	0 (0.0%)
8	Erosion of oral mucosa	1 (99.9%)	0 (0.0%)
9	Abnormal plasmablast proportion	1 (99.9%)	0 (0.0%)
10	Recurrent lower respiratory tract infections	1 (99.9%)	0 (0.0%)
11	Recurrent upper respiratory tract infections	1 (99.9%)	0 (0.0%)
12	Thrombocytopenia	1 (99.9%)	0 (0.0%)
13	(unusual) Respiratory tract infection	1 (99.9%)	0 (0.0%)
14	Abnormality of the tonsils	1 (99.9%)	0 (0.0%)
15	Septicaemia	1 (99.9%)	0 (0.0%)
16	Abnormal anus morphology	1 (99.9%)	0 (0.0%)
17	Increased proportion of plasmablasts	1 (99.9%)	0 (0.0%)
18	Azotemia	1 (99.9%)	0 (0.0%)
19	Pleural effusion	1 (99.9%)	0 (0.0%)
20	(unusual) Bacterial infection	1 (99.9%)	0 (0.0%)
21	Warts	1 (99.9%)	0 (0.0%)
22	Neutropenia	1 (99.9%)	0 (0.0%)
23	Lung disease	1 (99.9%)	0 (0.0%)
24	Anemia	1 (99.9%)	0 (0.0%)
25	Abnormal immunoglobulin level	1 (99.9%)	0 (0.0%)
26	Abnormality of the anus	1 (99.9%)	0 (0.0%)
27	Hyperuricemia	1 (99.9%)	0 (0.0%)
28	Hypergammaglobulinaemia	1 (99.9%)	0 (0.0%)
29	Unusual infection	1 (99.9%)	0 (0.0%)
30	Pleural empyema	1 (99.9%)	0 (0.0%)
31	Tonsillitis	1 (99.9%)	0 (0.0%)
32	Bronchitis	1 (99.9%)	0 (0.0%)
33	Abnormal neutrophil count	1 (99.9%)	0 (0.0%)
34	Abnormal platelet count	1 (99.9%)	0 (0.0%)
35	Perianal Abscess	1 (99.9%)	0 (0.0%)
36	Stomatitis	1 (99.9%)	0 (0.0%)
37	Cutaneous abscess	1 (99.9%)	0 (0.0%)
38	Pneumonia	1 (99.9%)	0 (0.0%)
39	Aphthous oral ulcer	1 (99.9%)	0 (0.0%)
40	Abnormal circulating nucleobase concentration	1 (99.9%)	0 (0.0%)
41	Abnormality of immune system physiology	1 (99.9%)	0 (0.0%)
42	Gingivitis	1 (99.9%)	0 (0.0%)
43	Abnormality of erythrocytes	1 (99.9%)	0 (0.0%)
44	Increased inflammatory response	1 (99.9%)	0 (0.0%)
45	Papilloma	1 (99.9%)	0 (0.0%)
46	Renal insufficiency	0 (0.0%)	1 (99.9%)
47	Chronic kidney disease	0 (0.0%)	1 (99.9%)

Age of onset
distribution

Summary of treatment outcomes