Detailed investigations of proximal tubular function in Imerslund-Gräsbeck syndrome

BMC Medical Genetics

Table 2 Functional characterisation of identified IGS causing mutations

Family	Gene	Genomic region	Protein prediction	Mutation type	Protein region	Low–molecular-weight Proteinuria	Predicted cubilin cell-surface expression
	*AMN*
1 and 2	c.208-2A>G ^A /c.208-2A>G	Intron 3	p.Leu70Alafs	Frameshift	Extracellular domain	Yes^*	No^A
3	c.1006 + 11_1008del/	Intron 9	p.Glu337Asnfs	Frameshift	Extracellular domain	Yes^*	No^{† and ♦}
3	c.1006 + 11_1008del	Intron 9	p.Glu337Asnfs	Frameshift	Extracellular domain	Yes^*	No^{† and ♦}
4	c.1041_1042delinsCTC/	Exon 10/	p.Glu348Serfs/	Frameshift/	Extracellular domain/	Yes^*	No^♦
4	c.208-2A>G ^A	intron3	p.Leu70Alafs	Frameshift	Extracellular domain	Yes^*	No^♦
	*CUBN*
5	c.3335G>A/c.3335G>A	Exon 24	p.Gly1112Glu	Missense	CUB 6	Yes^*	No^{† and ♦}
6	c.3890C>T/c.3890C>T ^B	Exon 27	p.Pro1297Leu	Missense	CUB 8	(no)^*	Yes^C

Table 2 summarises functional characterisation and protein predictions of the identified mutations including mutation classification, observations of low-molecular-weight proteinuria, prediction of cubilin membrane expression and receptor function. *Based on analyses of urinary excretion of selective cubilin and megalin ligands in patient urines using immunoblotting or high-resolution gel electrophoresis, see Table 3. ^†Based on in vitro functional analyses. ^♦Based on in silico protein predictions.^APreviously described as c.208-2A>G, skipping of exon 4, fs[5]. ^BPreviously described by [4]. ^CFunctional analyses previously described by [39].

ISSN: 1471-2350