Table 1 Summary of clinical features of patients carrying mutations in FCHO1.
Patient | Origin | Genetic varianta | Consequences of mutation | Immunological findings | Infections | Other clinical findings | Therapy and outcome |
|---|---|---|---|---|---|---|---|
A1 | Germany | FCHO1 c.2036 G > C | aa substitution in µHD domain (p.R679P) | • T- and B-cell lymphopenia • hypogammaglo-bulinemia | • Recurrent pneumonia and viral gastroenteritis • Relapsing oro-genital mycoses • Bronchiolitis obliterans • Postpneumonic pulmonary fibrosis • Otitis media | • Moya-Moya syndrome • Transient left hemiparesis upon cerebral ischaemia • Failure to thrive • Microcephaly | Reduced cardiopulmonary performance, stable Moya-Moya 9 years after HLA-matched HSCT |
B1 | Turkey | FCHO1 c.100 G > C | aa substitution in F-BAR domain (p.A34P) | • T- and B-cell lymphopenia • hypogammaglo-bulinemia | • Recurrent pneumonia • Recurrent fungal infections • CMV infection | • DLBCL • Renal metastases | Deceased as consequence of DLBCL, age 16 years |
C1 | Turkey | FCHO1 c.2023insG | Truncated (p.Stop687) | • CD4+ T-cell lymphopenia • hypogammaglo-bulinemia | • Recurrent pulmonary infections • Recurrent fungal infections • Otitis media | • EBV+ Hodgkin lymphoma • Failure to thrive • hepatosplenomegaly • Renal masses • Xanthogranulomatous pyelonephritis | IVIG replacement and antibiotics; awaiting allo-HSCT |
D1 | Turkey | FCHO1 c.2023insG | Truncated (p.Stop687) | • CD4+ T-cell lymphopenia • hypogammaglo-bulinemia | • Recurrent pneumonia • HSV infection | • DLBCL stage IV • Liver lesions • Spleen lesions • Lung lesions • Aphthous stomatitis • Gingivitis • Encephalitis | Deceased, age 10 years |
E1 | Palestine | FCHO1 c.489 + 1 G > A | Alternative splicing IVS8 splice donor | • CD4+ T-cell and B- lymphopenia • hypogammaglo-bulinemia | • Recurrent pneumonia • Chronic diarrhoea • CMV infection • Fungal infection | • Mild brain atrophy | IVIG replacement and antibiotics; awaiting allo- HSCT |
E2 | Palestine | FCHO1 c.489 + 1 G > A | Alternative splicing IVS8 splice donor | • not available | • Recurrent pneumonia • Chronic diarrhoea | Deceased after cardiac arrest, age 2 years | |
E3 | Palestine | FCHO1 c.489 + 1 G > A | Alternative splicing IVS8 splice donor | • CD4+ T-cell lymphopenia • hypogammaglo-bulinemia | • Recurrent pneumonia • Chronic diarrhoea • EBV infection | IVIG replacement and antibiotics; awaiting allo-HSCT | |
F1 | Saudi Arabia | FCHO1 c.195-2 A > C | Alternative splicing IVS6 splice acceptor | • CD4+ T-cell lymphopenia • hypogammaglo-bulinemia | • Recurrent pneumonia • Chronic diarrhoea • Cryptosporidiosis • Recurrent stomatitis (HSV) | • Failure to thrive | HSCT at age 5 yrs (no conditioning), MFD (mother), a + cGvHD, complete donor chimerism, normal immune function, off IVIG, 10 yrs follow up |
F2 | Saudi Arabia | FCHO1 c.195-2 A > C | Alternative splicing IVS6 splice acceptor | • CD4 + T-cell lymphopenia | • Recurrent pneumonia • Chronic diarrhoea • Cryptosporidiosis • Multiple viruses (adenovirus, RSV, enterovirus) | HSCT at age 1.5 yrs, (no conditioning), MSD, no GvHD, post-transplant intracranial EBV-PTLD and atypical mycobacterium-associated mastoiditis; mixed chimerism (T-cells 100% donor, non-T-MNCs 5-10% donor, red cells recipient), normal immune function, off IVIG, 12.5 yrs follow up | |
G1 | Algeria | FCHO1 c.1948C > T | Truncated p.R650X p.Stop650 | • CD4 + T-cell lymphopenia • Weak response to vaccination | • Recurrent broncho-pulmonary infections • Candidiasis • CMV infection | • Failure to thrive | HSCT (MFD) at age 5 years, doing well |
