Clinical characteristics of patients with MECOM mutations with high certainty of pathogenicity
| Patient . | Sex . | Hematological course . | HSCT (age in months) . | RUS . | Other skeletal malformations . | Other malformations . | Hearing . | Other/remarks . | Family history . | MECOM mutation (transcript variant 3) . |
|---|---|---|---|---|---|---|---|---|---|---|
| P1 | M | Congenital TP and anemia, progressive BMF | MUD (11) | Y | Hypoplasia of middle and end phalanx D5 | N | Normal | RUS in family members | c.2251C>T, p.His751Tyr | |
| P2 | M | Congenital TP, progressive BMF | First: MFD (8); second: MUD (21) | Y | N | N | Impaired (hearing aids) | RUS and RUSAT in family members | c.2276A>T, p.Gln759Leu | |
| P3 | M | Severely pancytopenic at birth but spontaneous amelioration during first weeks of life, persisting mild TP | N | Y | Clinodactyly D5, hypoplasia of middle phalanx D5 | N | ND | c.2278C>T, p.Pro760Ser | ||
| P4 | F | Congenital TP and anemia, progressive BMF | MUD (7) | Y | Toe malposition D2 bilateral | Cystic kidney (left), duplex kidney (right), urinary obstruction with megaureter (left) | Normal | Hypogammaglobulinemia | N | c.2208-1_2208delGA, loss of splice acceptor site |
| P5 | F | Severe congenital pancytopenia, progressive BMF | Died as a result of sepsis before HSCT | N | N | Hepatomegaly and mild bilateral renal calyceal dilatation | ND | Severe infections, B-cell deficiency | N | c.2248C>T, p.Arg750Trp |
| P6 | F | Severe congenital pancytopenia, extremely hypocellular BM | MUD (5), TRD | N | N | N | ND | Severe bacterial and fungal infections, GI bleeding | Healthy parents, 1 sister with Pierre Robin sequence, 1 sister with craniosynostosis | c.2248C>T, p.Arg750Trp |
| P7 | M | Congenital TP and anemia, progressive BMF | MUD (4), TRD | N | Brachymesophalangy D5 | Subpulmonary VSD, aortic coarctation | Normal | c.2542C>T, p.Arg848Ter | ||
| P8 | F | Congenital TP and anemia, progressive BMF | UCB (3) | N | N | ASD, small cleft palate | ND | Precocious puberty, cognitive deficits | c.69C>A, p.Cys23Ter | |
| P9 | M | Fetal adrenal hemorrhage (w30) resulting from TP, fast progression to pancytopenia and BMF | MUD (10.5), TRD | N | Thumb under D2 | N | Severe bacterial and fungal infections | c.2455+1G>C, loss of splice donor site | ||
| P10 | M | Pancytopenia | MFD (156) | N | Floating elbow, clinodactyly D5 | Tetralogy of Fallot | Congenital hearing loss | Niece with severe BMF (HSCT: MUD at age 8 mo); father hearing impaired | c.1114C>T, p.Gln372Ter | |
| P11 | F | Congenital TP, progressive BMF | MUD (16) | N | Hip dysplasia (left) | N | Inconspicuous | Gynecomastia in infancy (Tanner stage B3) | N | c.2419_2420insA, p.Arg807Kfs*7 |
| P12 | M | Mild TP at age 1 y, progressive BMF | MUD (85) | Y | Clinodactyly D5, brachydactyly D1 and D2, small patellae | N | Bilateral deafness | N | c.2296T>C, p.Cys766Arg |
| Patient . | Sex . | Hematological course . | HSCT (age in months) . | RUS . | Other skeletal malformations . | Other malformations . | Hearing . | Other/remarks . | Family history . | MECOM mutation (transcript variant 3) . |
|---|---|---|---|---|---|---|---|---|---|---|
| P1 | M | Congenital TP and anemia, progressive BMF | MUD (11) | Y | Hypoplasia of middle and end phalanx D5 | N | Normal | RUS in family members | c.2251C>T, p.His751Tyr | |
| P2 | M | Congenital TP, progressive BMF | First: MFD (8); second: MUD (21) | Y | N | N | Impaired (hearing aids) | RUS and RUSAT in family members | c.2276A>T, p.Gln759Leu | |
| P3 | M | Severely pancytopenic at birth but spontaneous amelioration during first weeks of life, persisting mild TP | N | Y | Clinodactyly D5, hypoplasia of middle phalanx D5 | N | ND | c.2278C>T, p.Pro760Ser | ||
| P4 | F | Congenital TP and anemia, progressive BMF | MUD (7) | Y | Toe malposition D2 bilateral | Cystic kidney (left), duplex kidney (right), urinary obstruction with megaureter (left) | Normal | Hypogammaglobulinemia | N | c.2208-1_2208delGA, loss of splice acceptor site |
| P5 | F | Severe congenital pancytopenia, progressive BMF | Died as a result of sepsis before HSCT | N | N | Hepatomegaly and mild bilateral renal calyceal dilatation | ND | Severe infections, B-cell deficiency | N | c.2248C>T, p.Arg750Trp |
| P6 | F | Severe congenital pancytopenia, extremely hypocellular BM | MUD (5), TRD | N | N | N | ND | Severe bacterial and fungal infections, GI bleeding | Healthy parents, 1 sister with Pierre Robin sequence, 1 sister with craniosynostosis | c.2248C>T, p.Arg750Trp |
| P7 | M | Congenital TP and anemia, progressive BMF | MUD (4), TRD | N | Brachymesophalangy D5 | Subpulmonary VSD, aortic coarctation | Normal | c.2542C>T, p.Arg848Ter | ||
| P8 | F | Congenital TP and anemia, progressive BMF | UCB (3) | N | N | ASD, small cleft palate | ND | Precocious puberty, cognitive deficits | c.69C>A, p.Cys23Ter | |
| P9 | M | Fetal adrenal hemorrhage (w30) resulting from TP, fast progression to pancytopenia and BMF | MUD (10.5), TRD | N | Thumb under D2 | N | Severe bacterial and fungal infections | c.2455+1G>C, loss of splice donor site | ||
| P10 | M | Pancytopenia | MFD (156) | N | Floating elbow, clinodactyly D5 | Tetralogy of Fallot | Congenital hearing loss | Niece with severe BMF (HSCT: MUD at age 8 mo); father hearing impaired | c.1114C>T, p.Gln372Ter | |
| P11 | F | Congenital TP, progressive BMF | MUD (16) | N | Hip dysplasia (left) | N | Inconspicuous | Gynecomastia in infancy (Tanner stage B3) | N | c.2419_2420insA, p.Arg807Kfs*7 |
| P12 | M | Mild TP at age 1 y, progressive BMF | MUD (85) | Y | Clinodactyly D5, brachydactyly D1 and D2, small patellae | N | Bilateral deafness | N | c.2296T>C, p.Cys766Arg |
HSCT outcome was positive unless otherwise indicated.
ASD, atrial septal defect; F, female; GI, gastrointestinal; M, male; MFD, matched family donor; MUD, matched unrelated donor; ND, no data; TP, thrombocytopenia; TRD, transplantation-related death; UCB, unrelated cord blood.