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 |
EBV Epstein–Barr virus, DLBCL diffuse large B-cell lymphoma, PTLD post-transplant lymphoproliferative disorder, HLA human leucocyte antigen, HSCT haematopoietic stem cell transplantation, MFD matched family donor, IVIG intravenous immunoglobulin, a + cGvHD acute and chronic graft versus host disease.
aSequence of coding DNA is given from the first nucleotide of the translation start codon.
bSequence of protein is given from the first amino acid.