Table 2.
Characteristics of the GALC gene gene mutations identified in the 30 Krabbe disease patients and MutPred analysis of the missense mutations
| MutPred analysisof missense mutations# | |||||||
|---|---|---|---|---|---|---|---|
| Location | Site of nucleotide substitution* | Amino acid change** | Traditional numbering nucleotide (amino acid) substitution | Type of mutation | Probability of deleterious mutation | Confident in silico hypotheses | References |
| Ex. 1 | c.61delG | p.A21RfsX51 | Frameshift | - | Present study | ||
| c.175G>C | p.G59R | 127G>C (G43R) | Missense | 0.92 | None | Fu et al.(1999) | |
| c.205T>C | p.R69X | Nonsense | - | Present study | |||
| Ex.2 | c.236G>A | p.R79H | 188G>A(R63H) | Missense | 0.85 | None | De Gasperi et al. (1996) |
| c.262A>T | p.K88X | Nonsense | - | Present study | |||
| Ex.3 | c.302_308dupAAATAGG | p.G102GfsX5 | Frameshift | - | Present study | ||
| c.379C>T | p.R127X | Nonsense | - | Present study | |||
| Ex. 4 | c.388G>A | p.E130K | 340G>A(E114K) | Missense | 0.80 | Gain of molecular recognition feature (MoRF) binding (P=0.0047), Gain of methylation at E130 (P=0.0114), Gain of ubiquitination at E130 (P=0.0269) | Lissens et al.(2007) |
| c.408delA | p.E136EfsX35 | Frameshift | - | Present study | |||
| Ex. 5 | c.521delA | p.Y174LfsX3 | Frameshift | - | Present study | ||
| c.560A>T | p.D187V | 512A>T(D171V) | Missense | 0.71 | None | Luzi et al. (1996) | |
| Ex. 7 | c.749T>C | p.I250T | 701T>C(I234T) | Missense | 0.79 | Gain of protein disorder (P=0.0309), Loss of beta sheet secondary structure (P=0.0392) | De Gasperi et al. (1996) |
| c.857G>A | p.G286D | 809G>A(G270D) | Missense | 0.98 | None | Furuya et al. (1997) | |
| Ex. 8 | c.884A>C | p.N295T | 836A>C(N279T) | Missense | 0.80 | None | Wenger et al. (1997) |
| c.918C>T | p.S303F | 870C>T(S287F) | Missense | 0.83 | None | Wenger et al. (1997) | |
| c.941A>G | p.Y314C | 893A>G(Y298C) | Missense | 0.89 | None | De Gasperi et al. (1996) | |
| Ex. 9 | c.953C>G | p.P318R | Missense | 0.79 | Increased solvent accessibility (P=0.0179), Loop > Helix secondary structure change (P=0.0259) | Present study | |
| c.967G>A | p.G323R | Missense | 0.91 | None | Present study | ||
| Ex. 10 | c.1075_1084delAAGACAGTTG | p.K359AfsX3 | 1027_1036delAAGACAGTTG§(K343AfsX3) | Frameshift | - | Wenger et al. (1997) | |
| c.1151T>C | p.I384T | Missense | 0.74 | None | Present study | ||
| Intr. 10 | c.1161+6532_polyA+9Kbdel | IVS10del30kb | Deletion | - | Rafi et al. (1995) | ||
| d 171_1175delCATTCinsA | p.H391IfsX65 | Frameshift | - | Present study | |||
| Ex.11 | c.1186C>T | p.R396W | 1138C>T(R380W) | Missense | 0.96 | Loss of protein disorder (P=0.0371) | Wenger et al. (1997) |
| c.1187G>T | p.R396L | 1139G>T(R380L) | Missense | 0.95 | Gain of ubiquitination at K393 (P=0.0452) | Selleri et al. (2000) | |
| Ex. 13 | c.1405_1407delCTCinsT | p.L469YfsX22 | Frameshift | - | Present study | ||
| c.1468T>A | p.Y490N | Missense | 0.68 | Loss of phosphorylation at Y490 (P=0.0245) | Present study | ||
| Intr. 13 | c.1489+1G>A | p.S488NfsX200 | Splicing | - | Present study | ||
| Ex. 14 | c.1586C>T | p.T529M | 1538C>T(T513M) | Missense | 0.68 | None | Wenger et al. (1997) |
| c.1657G>A | p.G553R | 1609G>A(G537R) | Missense | 0.91 | Sheet > Helix secondary structure change (P=0.0151) | De Gasperi et al. (1999) | |
| c.1700A>C | p.Y567S | 1652A>C(Y551S) | Missense | 0.73 | None | Wenger et al. (1997) | |
| Ex. 15 | c.1787delT | p.F596SfsX16 | 1739delT(F580SfsX16) | Frameshift | - | Selleri et al. (2000) | |
| c.1819_1826dupGTTACAGG | p.G609GfsX6 | Frameshift | - | Present study | |||
| Ex. 16 | c.1901delT | p.L634X | 1853delT(L618X) | Nonsense | - | Wenger et al. (1997) | |
Legend: Ex=exon; Intr=intron; *GALC gene GenBank-EMBL accession no. NM_000153.2; **GALC gene GenBank-EMBL accession no. NP_000144.2; the novel mutations are given in bold; §mutation reported as c.1026del10 by Rafi et al., unpubished observations [Wenger et al., 2007]. #Li et al., (2009) and Mort et al., (2010).