Table 2.
Summary of GSD mutations detected by MPS-GSD panel.
| Patients /gender/GSD type | Age at genetic diagnosis | Gene/inheritance patterna | Chr: loc (hg19) | Nucleotide change | Predicted protein change | Variant type | Zygosity | Feature of liver histopathology | Previous definition and pathogenicity | Iranome database |
|---|---|---|---|---|---|---|---|---|---|---|
| P1/F/Ib | 14 mo | SLC37A4/AR | 11: 118900056 | c.24T > G | p.Tyr8Ter | Nonsense | Homozygous | GSD I with severe fibrosis, cirrhosis | Not defined, Pathogenic | NA |
| P2/F/III | 41mo | AGL/AR | 1: 100336041 | c.753_756delCAGA | p.Asp251GlufsTer23 | In-frame deletion | Homozygous | GSD I or III with early septal cirrhosis | Defined in HGMD, pathogenic | NA |
| P3/M/III | 29 mo | AGL/AR | 1: 100336041 | c.753_756delCAGA | p.Asp251GlufsTer23 | In-frame deletion | Homozygous | GSD I or III with mild portal fibrosis | Defined in HGMD, pathogenic | NA |
| P4/F/III | 47 mo | AGL/AR | 1: 100342081 | c.1351_1355delAAAGC | p.Lys451LeufsTer14 | Frame shift | Homozygous | GSD I or III with severe fibrosis | Not defined, pathogenic | NA |
| P5/M/III | 36 mo | AGL/AR | 1: 100379113 | c.3980G > A | p.Trp1327Ter | Nonsense | Homozygous | GSD I or III with cirrhosis | Defined in HGMD, pathogenic | NA |
| P6/M/IV | 51 mo | GBE1/AR |
3: 81643169 3: 81754616 |
c.998A > T c.292G > C |
p.Glu333Val p.Val98Leu |
Missense Missense |
Homozygous Homozygous |
GSD IV with cirrhosis |
Defined in HGMD, pathogenic Not defined, uncertain significance |
NA NA |
| P7/F/VI | 48 mo | PYGL/AR | 14: 51378453 | c.1964A > G | p.Glu655Gly | Missense | Homozygous | Unclassified GSD with marked fibrosis | Not defined, uncertain significance | NA |
| P8/M/VI | 19 mo | PYGL/AR | 14: 51410891 | c.229_231delGAC | p.Asp77del | Deletion | Homozygous | GSD I or III with fibrosis | Defined in HGMD, pathogenic | NA |
| P9/F/IXc | 28 mo | PHKG2/AR | 16: 30762461 | c.130C > T | p.Arg44Ter | Nonsense | Homozygous | Unclassified GSD with fibrosis | Defined in HGMD, pathogenic | NA |
| P10/M/IXb | 36 mo | PHKB/AR | 16: 47531367 | c.134T > A | p.Leu45His | Missense | Heterozygous | Unclassified GSD with bridging fibrosis | Not defined, uncertain significance | 0.0025 |
| P11/F/Ib, IXb | 41 mo |
SLC37A4/AR PHKB/AR PHKB/AR |
11: 118898407 16: 47628046 16: 47727384 |
c.337C > T c.1127-2A > G c.2840A > G |
p.Leu113Phe p.? p.Gln947Arg |
Missense Potential splice site Missense |
Heterozygous Homozygous Homozygous |
Unclassified GSD with moderate periportal fibrosis |
Not defined, uncertain significance Not defined, likely pathogenic Not defined, uncertain significance |
0.003125 NA NA |
| P12/M/X | 29 mo | PGAM2/AR | 7: 44105115 | c.14G > A | p.Arg5His | Missense | Heterozygous | Unclassified GSD with early septal cirrhosis | Not defined, uncertain significance | NA |
| P13/F/GSD of heart, lethal congenital | 29 mo | PRKAG2/AD | 7: 151329185 | c.592A > T | p.Met198Leu | Missense | Heterozygous | Unclassified GSD with cirrhosis | Not defined, uncertain significance | NA |
| P14/F/NA | 28 mo | NA | – | None in GSD or similar phenotype genes | – | – | – | Unclassified GSD or lipid storage disease with mild portal fibrosis | – | – |
Bold type represents novel unclassified variants.
AD autosomal dominant, AR autosomal recessive, Chr Loc chromosome location, F female, GSD glycogen storage disease, HGMD human gene mutation database, M male, mo month, P patient, VUS variant of unknown significance.
aThe Accession Number of the relevant reference sequence(s): SLC37A4, RefSeq NM_001164279.2; AGL, Ref Seq NM_000642.3; GBE1, RefSeq NM_000158.4; PYGL, RefSeq NM_002863.5; PHKG2, RefSeq NM_000294.3; PHKB, RefSeq NM_000293.3; PGAM2, RefSeq NM_000290.4; PRKAG2, RefSeq NM_001040633.1.