Table 1.
Clinical and molecular data of eight JSRD families with biallelic TMEM67 mutations
Family data | Clinical data | Genetic data | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
| ||||||||||||
Family | Age (sex) | Origin | CNS | Eye | kidney | liver | other | Nucleotide changes | Exon | Effects on protein | Tr | |
COR47 | NG 1604 | 8(M) | IT | MT EV | Co | - (8) | ELE | c.370G>A | 3 | p.E124K + | P | |
NG 2001 | 4(F) | MTS | ONH | - (4) | ELE | c.1073C>T | 11 | p.P358L +++ | M | |||
| ||||||||||||
COR113 | NG 2016 | 3(M) | IT | MTS | Co(L) | - (3) | LI | c.1706G>A | 17 | p.G569D ++ | P | |
c.G1860+1G>A | 18 | Splice | M | |||||||||
| ||||||||||||
COR143 | NG 2038 | 1(F)* | SW | MTS | Co | UCD | ELE | c.1285C>T | 12 | p.Q429X | M | |
c.1847C>T | 18 | p.A616V + | P | |||||||||
| ||||||||||||
COR212 | NG 2358 | 15(F) | IT | MTS | Co | cysts, CRI (6m) | HSM ELE | c.1115C>A | 11 | p.T372K ++ | M | |
c.2216T>G | 21 | p.L739R ++ | P | |||||||||
| ||||||||||||
COR240 | NG 2367 | 5(M) | IT | MTS | - | - (5) | HSM ELE LI | c.1077_1078 | 11 | p.T360RfsX18 | M | |
c.1769T>C | 17 | p.F590S ++ | P | |||||||||
| ||||||||||||
COR265 | NG 2511 | 23(M) | IT | MTS | Co(L) | - (23) | CHF | PD(4) | c.270T>G | 2 | p.N90K ++ | M |
c.755T>C | 8 | p.M252T +++ | P | |||||||||
| ||||||||||||
COR266 | NG 2515 | 4(F) | GE | MTS | Co | - (2) | CHF | c.300C>A | 2 | p.C100X | M | |
c.2498T>C | 24 | p.I833T ++ | P | |||||||||
| ||||||||||||
COR254 | NG 2466 | 8(M) | GE | MTS | - | - (8) | ELE | c.903C>G | 9 | p.D301E + | M | |
c.1538A>G | 15 | p.Y513C+++ | P |
CHF: congenital hepatic fibrosis; Co: chorioretinal colobomas; CRI: chronic renal insufficiency; ELE: elevated liver enzymes; EV: enlarged ventricles; HSM: hepatosplenomegaly; IUGR: intrauterine growth retardation; (L): left eye only; LI: liver imaging consistent with ductal plate malformation; M: maternal; MTS: molar tooth sign; ONH: optic nerve hypoplasia; P: paternal; PD: polydactyly (number of limbs); Tr: transmission; UCD: urinary concentration defect. Origin: IT: Italy; SW: Sweden; GE: Germany.
One pregnancy terminated for prenatal diagnosis of JSRD. PolyPhen prediction: benign:
possibly damaging:
probably damaging:
Novel mutations are in bold.