Table 2. Summary of the genotype–phenotype correlation of Arab patients with Krabbe disease.
| Origin | Phenotype | Nucleotide change | Amino acid change | PP (S,S,S) | GALC_EA | PN | References |
|---|---|---|---|---|---|---|---|
| Muslim Arab (Dx Israel) | EIKD | c.1582G > A | p.D528Na | PrD (1,0,1) | Loss | 1 | Rafi et al31 |
| Muslim Arab (Dx Israel) | (EIKD) | c.1637 T > C | p.I546T | PsD (0.46,0.89,0.90) | b | 1 | Rafi et al31 |
| Druze (Dx Israel) | EIKD | c.1748 T > G | p.I583S | PrD (0.99, 0.27, 0.99) | Loss | 1 | Rafi et al31 |
| Morocco (Dx France) | LOKD | c.147G > C | p.G49G | NA | NR | 1 | Debs et al20 |
| Morocco (Dx France) | LOKD | c.1637T > C | p.I546T | PsD (0.459,0.89,0.90) |
c | 1 | Debs et al20 |
| Saudi Arabia | EIKD | c.860 C > Td | p.S287F* | PrD (1,0,1) | Loss | 1 | Wenger et al7; Jardim et al70 |
| Arab | EIKD | c.154T > C | p.S52P* | PrD (1,0,1) | NR | 1 | Wenger et al8 |
Abbreviations: Dx, diagnosed in; EIKD, early infantile Krabbe disease; EIKD, the variant itself is not known to cause the EIKD phenotype and considered as polymorphic variant (see text), GALC_EA, galactocerebrosidase enzyme activity of normal; LOKD, late onset Krabbe disease; Loss, ındicates complete absence of GALC activity; NA, not applicable; ND, not determined due to lack of studies on the subject; NR, not reported; PN, number of patients studied; PP, PolyPhen-2 (http://genetics.bwh.harvard.edu) prediction; PrD, probably damaging; PsD, possibly damaging; S,S,S, score, sensitivity, specificity.
Note: The GALC sequence used as a template for the in silico prediction has accession # AAA16645, version: AAA16645.1, and GI: 431310. The GALC reference sequence has accession # L23116 (+1 as A of the ATG start codon), version: L23116.1.
These mutations predicted with SIFT (http://sift.jcvi.org) as not tolerated.
The in vitro expression of this mutant resulting in decreased but not deficient GALC activity, and has been found in the heterozygous and homozygous state in healthy individuals and is therefore considered to be a polymorphism.29
The activity is reported to be reduced and there was no exact measurement of the GALC activity.70
This variant mentioned as unpublished observation by Wenger et al,7 described as infantile, no more information published about this patient thus far.