PHKA2 mutation spectrum in Korean patients with glycogen storage disease type IX: prevalence of deletion mutations

Table 4 Reported PHKA2 mutations in Asian patients with glycogen storage disease (GSD) type IX

Ethnicity	Exon number	Nucleotide change	Amino acid change	Mutation type	Reference
Point mutation
Chinese	2	c.136delG	p.Asp46Ilefs*37	Frameshift	[31]
Japanese	4	c.346 T > G	p.Tyr116Asp	Missense	[32]
Japanese	6	c.578G > T	p.Gly193Val	Missense	[32]
Japanese	9	c.883C > T	p.Arg295Cys	Missense	[25]
Korean	9	c.884G > A^a	p.Arg295His	Missense	[8], This study
Japanese	15	c.1489C > T	p.Arg497*	Nonsense	[25]
Japanese	16	c.1697A > T	p.Ile566Asn	Missense	[33]
Japanese	32	c.3505C > T	p.Gln1169*	Nonsense	[25]
Japanese, Chinese^b	33	c.3614C > T	p.Pro1205Leu	Missense	[22, 24, 32, 34]
Splicing mutation
Japanese	2	c.79-1G > T	Exon 2 skipping	Splicing	[25]
Korean	IVS5	c.537 + 5G > A	?^c	Splicing	[6], This study
Japanese	25	c.2675A > G	Exon 25 skipping	Splicing	[32]
Chinese	30	c.3112-1G > A	Exon 30 skipping	Splicing	[31]
Deletion mutation
Korean	30	c.3210_3212delGAG	p.Arg1072del	Small deletion	[18, 19], This study
Korean	8		Exon 8 deletion	Gross deletion	[13], This study
Korean	18–33		Exon 18–33 deletions	Gross deletion	This study
Japanese	20–26		Exon 20–26 deletions	Gross deletion	[29]
Korean	27–33		Exon 27–33 deletions	Gross deletion	[6], This study

^aThis mutation has been reported previously in two patients with GSD IX and is predicted to affect protein function by in silico analyses (SIFT and PolyPhen-2) and to affect splicing, potentially through activation of an exonic cryptic donor site, by both Human Splice Finder software and by a machine-learning technique that scores how strongly genetic variants affect RNA splicing [27]
^bThis mutation has been reported as a founder mutation in the Dutch population
^cAlthough in vitro analysis for the splicing effect of c.537 + 5G > A was not performed, in vivo results confirming phosphorylase b kinase deficiency have been reported to constitute a pathogenic mutation in a patient with GSD IX in previous literature. This mutation was predicted to affect splicing, potentially through alteration of the wild-type donor site

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