Table 1.
CBS analysis—pathogenic mutations found in patients with classical homocystinuria (n = 35)
| Patient | Sex | Origin (Brazilian region) | Allele 1 | Allele 2 | Cons. | Age at inclusion (years) | Age of onset (years) | B6 response found | B6 response expecteda | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| cDNA | Protein | cDNA | Protein | ||||||||
| 1a | M | S | c.253G>Ac | p.Gly85Arg | c.253G>A | p.Gly85Arg | Y | 36 | 6 | N | N |
| 1b | F | S | c.253G>Ac | p.Gly85Arg | c.253G>A | p.Gly85Arg | Y | 27 | NA | N | N |
| 1c | F | S | c.253G>Ac | p.Gly85Arg | c.253G>A | p.Gly85Arg | Y | 31 | 7 | N | N |
| 2 | M | S | c.833T>C | p.Ile278Thr | c.833T>C | p.Ile278Thr | Y | 35 | 0.2 | Y | Y |
| 3 | M | S | c.833T>C | p.Ile278Thr | c.833T>C | p.Ile278Thr | N | 35 | 7 | Y | Y |
| 4 | F | SE | c.833T>Cc | p.Ile278Thr | c.833T>Cd | p.Ile278Thr | Y | 18 | 15 | Y | Y |
| 5 | M | SE | c.833T>C | p.Ile278Thr | c.28delG | p.Val10 fs | N | 26 | 1 | Y | Y/Nb |
| 6 | M | SE | c.833T>C | p.Ile278Thr | c.451G>A | p.Gly151Arg | N | 23 | 4 | Y | Y/Nb |
| 7 | F | S | c.833T>C | p.Ile278Thr | c.989_991delAGG | p.(Glu330del) | N | 28 | 20 | N | Y/Nb |
| 8 | M | NE | c.833T>C | p.Ile278Thr | c.828+1G>A | p.? | N | 16 | 4 | N | Nb |
| 9 | F | S | c.828+1G>Ac | p.? | c.1126G>A | p.Asp376Asn | N | 23 | 5 | N | Nb |
| 10 | M | SE | c.828+1G>Ad | p.? | c.2T>C c | p.? | N | 13 | 1 | N | Nb |
| 11 | F | S | c.828+1G>A | p.? | c.691G>C | p.Ala231Leu | N | 13 | 1 | N | Nb |
| 12 | M | NE | c.828+1G>A | p.? | c.828+1G>A | p.? | Y | 8 | 1 | N | Nb |
| 13 | M | SE | c.572C>T | p.Thr191Met | c.572C>T | p.Thr191Met | Y | 26 | 19 | N | N |
| 14 | M | SE | c.572C>T | p.Thr191Met | c.572C>T | p.Thr191Met | Y | 10 | 5 | N | N |
| 15 | F | S | c.572C>T | p.Thr191Met | c.572C>T | p.Thr191Met | Y | 18 | 5 | N | N |
| 16 | M | SE | c.572C>T | p.Thr191Met | c.572C>T | p.Thr191Met | Y | 19 | 4 | N | N |
| 17 | M | S | c.572C>T | p.Thr191Met | c.209+1delG c | p.? | N | 14 | 8 | N | Nb |
| 18a | M | SE | c.969G>Ac | p.Trp323Ter | c.969G>Ad | p.Trp323Ter | Y | 17 | 6 | N | NA |
| 18b | M | SE | c.969G>Ac | p.Trp323Ter | c.969G>Ad | p.Trp323Ter | Y | 6 | 1 | N | NA |
| 19 | M | NE | c.969G>A | p.Trp323Ter | c.969G>A | p.Trp323Ter | N | 15 | 1 | N | NA |
| 20 | M | NE | c.969G>A | p.Trp323Ter | c.969G>A | p.Trp323Ter | N | 10 | 7 | N | NA |
| 21a | M | SE | c.451G>A | p.Gly151Arg | c.451G>A | p.Gly151Arg | Y | 15 | 7.5 | N | N |
| 21b | F | SE | c.451G>A | p.Gly151Arg | c.451G>A | p.Gly151Arg | Y | 14 | NA | N | N |
| 22 | F | SE | c.451G>A | p.Gly151Arg | c.451G>A | p.Gly151Arg | Y | 17 | 3 | N | N |
| 23 | M | S | c.284T>C c | p.Ile95Thr | c.284T>C | p.Ile95Thr | Y | 18 | 1 | N | NA |
| 24 | M | S | c.1058C>Tc | p.Thr353Met | c.146C>T | p.Pro49Leu | N | 19 | 3 | Y | Yb |
| 25 | F | S | c.1126G>Ac | p.Asp376Asn | c.1126G>Ad | p.Asp376Asn | Y | 14 | 1.5 | N | N |
| 26 | M | S | c.444delG c | p.(Asn149 fs ) | c.444delG | p.(Asn149 fs ) | Y | 22 | 1.5 | N | NA |
| 27 | M | NE | c.329A>T | p.Glu110Val | c.770C>T | p.Thr257Met | N | 16 | 3 | N | Nb |
| 28a | F | NE | c.1223+5G>T | p.? | c.1223+5G>T | p.? | Y | 5 | 3 | NA | NA |
| 28b | F | NE | c.1223+5G>T | p.? | c.1223+5G>T | p.? | Y | 7 | 3 | NA | NA |
| 29 | F | CW | c.864_868delGAG | p.(Glu289del) | c.864_868delGAG | p.(Glu289del) | Y | 17 | 6 | N | NA |
| 30 | M | SE | c.209+1G>A | p.? | NI | NI | N | 37 | 6 | N | Nb |
Novel mutations are set in bold. Patients represented by the same number belong to the same family. M, male; F, female; S, south; SE, southeast; NE, northeast; CW, central‐west; Cons, consanguinity; Y, yes; N, no; B6, pyridoxine; NA, not available; NI, not identified.
a
According to previously described cases in the literature (Kraus, 2017), all partially responsive patients were considered as nonresponsive.
b
Estimated; no identical genotype reported previously.
c
Mother heterozygous for mutation.
d
Father heterozygous for mutation.