Table 3.

CD46 cell surface expression and genetic analysis in patients with aHUS

Patients	MFI, %	cDNA position of mutation; amino acid change	In silico prediction/functional studies	Classification	Zygosity
1	59.4	Intron 12; c.1127 + 46C>Ga	Activation of intronic cryptic acceptor site; potential alteration of splicing	Novel	Heterozygous
2	10.4	Intron 2; c.286 + 2T>Gc	Defective splicing causing protein truncation	Previously reported	Homozygous
3	10.4	Intron 2; c.286 + 2T>Gc	Defective splicing causing protein truncation	Previously reported	Homozygous
4	69.4	Exon 8; c.911C>Ta,b, Missense (p.S304F)	Alteration of exonic splicing enhancer site; possibly damaging	Novel	Heterozygous
5	–	Intron 4; c.475 + 33A>Ga	Activation of intronic cryptic donor site; potential alteration of splicing	Variant of unknown significance, MAF <0.01% (ExAC)	Heterozygous
6	9.5	Intron 2; c.286 + 2T>Gc	Defective splicing causing protein truncation	Previously reported	Heterozygous
7	12.8	Intron 2; c.286 + 2T>Gc	Defective splicing causing protein truncation	Previously reported	Homozygous
8	16.0	Intron 2; c.286 + 2T>Gc	Defective splicing causing protein truncation	Previously reported	Homozygous
9	8.5	Exon 2; c.104G>Ad, Missense (p.C35Y)	Formation of aberrant precursor protein; alteration of exonic splicing enhancer site	Previously reported	Homozygous
10	58.2	Exon 5; c.565T>Gb,c, Missense (p.Y189D)	Formation of aberrant precursor protein, probably damaging	Previously reported, MAF 0.02% (1000 genome)	Heterozygous

Disease occurred sporadically in all, except Patients 9 and sibling pairs Patients 2–3 [14] and 7–8 whose parents were heterozygous for the same mutation.

ExAC, Exome Aggregation Consortium; MAF, minor allele frequency by public databases; MFI, median fluorescence intensity.

^aIn silico prediction by Human Splicing Finder (HSF) version 2.4.1.

^bIn silico prediction by PolyPhen-2.

Previously reported functional studies: ^c[15] and ^d[3, 5, 16].