. 2013 Sep 19;24(12):1945–1954. doi: 10.1681/ASN.2012100985

Table 1.

Pathogenic COL4A3 and COL4A4 mutations detected in 40 patients with autosomal recessive Alport syndrome

Patient No.	H/h	COL4A3/COL4A4	Mutation 1	Exon	Novel?	Mutation 2	Exon	Novel?	Sex	Ethnicity	Age (yr)^a	Age at Renal Failure (yr)	Renal Biopsy	Hearing Loss	Characteristic Eye Signs	Notes
1	h	COL4A3	c.162dup	3	Yes	c.2313_2330del	30	Yes	M	Tasmanian family, British origin generations ago	34	23	Yes	Yes	Yes	Mutations in trans
			p.(Gly55fs)^b			p.(Leu775_Gly780del)
2	h	COL4A3	c.391G>T	7	Yes	c.2621_2622delinsT	32	No, AR AS, H, h⁸	F	Australian family probably originally from UK	38	15	Yes	Yes	Yes
			p.(Glu131*)^b			p.(Gly874fs)^b
3	h	COL4A3	c.461G>C	8	Yes	c.794G>A	14	Yes	M	English	44	37	Yes	No	No	Mutations in trans
			p.(Gly154Ala)			p.(Gly265Glu)
4	h	COL4A3	c.546G>T	9	Yes	c.4981C>T	52	No, AR AS, h⁸	F	Australian family, probably originally from UK	38	N/A	Yes	Yes	No	c.546G>T has splice effect
			p.(Gln182His)			p.(Arg1661Cys)
5	h	COL4A3	c.663_664del	12	Yes	c.1937dup	27	Yes	F	English	10	N/A (N @ 9)	Yes	No	NK	Mutations in trans
			p.(Arg221fs)^b			p.(Glu647fs)^b
6	h	COL4A3	c.713del	13	Yes	c.1918G>A	26	No, AR AS⁸	F	NK	21	N/A (N @ 17)	N @ 6	No	No
			p.(Pro238fs)^b			p.(Gly640Arg)
7	h	COL4A3	c.1085del	19	Yes	c.3580del	42	Yes	M	NK	6	N/A (N @ 6)	Yes	No	NK	Mutations in trans
			p.(Pro362fs)^b			p.(Arg1194fs)^b
8	H	COL4A3	c.1409–5T>A	22i	No, AR AS¹⁸	c.1409–5T>A	22i	No, AR AS¹⁸	M	Australian, parents were Italian	54	38	Yes	Yes	Yes	Apparent homozygous. Parents first cousins
9	h	COL4A3	c.2031_2038dup	28	Yes	c.3472G>C	40	Yes	M	NK	Deceased	26	Yes	Yes	No
			p.(Gly680fs)^b			p.(Gly1158Arg)
10	h	COL4A3	c.2031_2038dup	28	Yes	c.3210+1G>A	37i	Yes	M	NK	41	10	Yes	Yes	Yes
			p.(Gly680fs)^b
11	h	COL4A3	c.2083G>A	28	No, TBMN²⁷	c.2452G>A	31	Yes	M	English	19	N/A (N @ 18)	Yes	No	NK	Mutations in trans
			p.(Gly695Arg)			p.(Gly818Arg)
12	H	COL4A3	c.2567G>A	32	Yes	c.2567G>A	32	Yes	M	NK	16	N/A (N @ 16)	Yes	Yes	No	Apparent homozygous; father heterozygous
			p.(Gly856Glu)			p.(Gly856Glu)
13	h	COL4A3	c.2621_2622delinsT	32	No, AR AS, H and h⁸	c.3866del	43	Yes	F	NK	40	17	Yes	Yes	Yes
			p.(Gly874fs)^b			p.(Gly1289fs)^b
14	h	COL4A3	c.2745_2746+7del	33–33i	Yes	c.4981C>T	52	No, AR AS, h⁸	F	NK	14	NK	Yes	No	No	Mutations in trans
			p.(Gly916fs)^b			p.(Arg1661Cys)
15	H	COL4A3	c.2768_2778del	34	Yes	c.2768_2778del	34	Yes	F	Australian family, probably originally from UK	44	25	Yes	Yes	Yes	Confirmed homozygous; consanguineous
			p.(Val923fs)^b			p.(Val923fs)^b
16	h	COL4A3	c.2768_2778del	34	Yes	c.4981C>T	52	No, AR AS, h⁸	F	NK	49	NK	NK	NK	NK	Mutations in trans
			p.(Val923fs)^b^,^c			p.(Arg1661Cys) +
17	h	COL4A3	c.2768_2778del	34	Yes	c.3760G>C	43	Yes	F	Mixed British	36	23	Yes	Yes	Yes
			p.(Val923fs)^b^,^c			p.(Gly1254Arg) +
18	h	COL4A3	c.3472G>C	40	Yes	c.4994G>A	52	Yes	F	English	17	N/A (N @ 17)	TBM@5	No	NK	Mother has one mutation
			p.(Gly1158Arg)			p.(Cys1665Tyr)
19	h	COL4A3	c.4030del	46	Yes	c.4408G>T	48	Yes	M	Punjabi	8	N/A (N @ 7)	Yes	No	NK	Mother has one mutation
			p.(Val1344fs)^b			p.(Gly1470Trp)
20	H	COL4A3	c.4347_4353del	48	Yes	c.4347_4353del	48	Yes	M	NK	31	17	Yes	Yes	NK	Apparent homozygous. Nonconsanguineous
			p.(Arg1450fs)^b			p.(Arg1450fs)^b
21	h	COL4A4	c.81_86del	3	Yes	c.2906C>G	32	No, AR AS, TBMN^9,11,18,19	F	NK	15	NK	Yes	NK	NK	Father has one mutation
			p.(Ile29_Leu30del)			p.(Ser969*)^b
22	h	COL4A4	c.81_86del	3	Yes	c.2906C>G	32	No, AR AS, TBMN^9,11,18,19	M	NK	10	NK	Yes	NK	NK
			p.(Ile29_Leu30del)			p.(Ser969*)^b
23	h	COL4A4	c.1099+1G>A	18i	Yes	c.2638del	30	No, AR AS⁹	M	Tasmanian family, likely originally from UK	30	23	Yes	Yes	Yes
						p.(Ala880fs)^b
24	H	COL4A4	c.1598G>A	22	Yes	c.1598G>A	22	Yes	F	NK	20	N/A (N @ 20)	Yes	No	NK	Confirmed homozygous
			p.(Gly533Asp)			p.(Gly533Asp)
25	H	COL4A4	c.1598G>A	22	Yes	c.1598G>A	22	Yes	F	Slovakian	30	N/A (N @ 30)	NK	Yes	NK	Confirmed homozygous Nonconsanguineous
			p.(Gly533Asp)			p.(Gly533Asp)
26	H	COL4A4	c.1802del	24	No, AR AS⁷	c.1802del	24	No, AR AS⁷	F	NK	20	N/A (N @ 20)	Yes	No	No	Apparent homozygous; some consanguinity
			p.(Pro601fs)^b			p.(Pro601fs)^b
27	h	COL4A4	c.2590G>A	30	No, AR AS¹⁵	c.2906C>G	32	No, AR AS, TBMN^9,11,18,19	F	NK	42	N/A	Yes	No	No	Mutations in trans
			p.(Gly864Arg)			p.(Ser969*)^b
28	h	COL4A4	c.2638del	30	No, AR AS⁹	c.2884G>T	32	Yes	M	Australian	32	28	NK	NK	NK
			p.(Ala880fs)^b			p.(Glu962*)^b
29	H	COL4A4	c.2638del	30	No, AR AS⁹	c.2638del	30	No, AR AS⁹	M	NK	20	NK	Yes	Yes	NK	Confirmed homozygous
			p.(Ala880fs)^b			p.(Ala880fs)^b
30	h	COL4A4	c.2744del	31	No, AR AS⁹	c.3197G>T	34	Yes	F	Australian family, likely originally from UK	28	35	NK	NK	NK
			p.(Gly915fs)^b			p.(Gly1066Val)
31	h	COL4A4	c.2906C>G	32	No, AR AS, TBMN^9,11,18,19	c.3215G>T	35	Yes	F	NK	23	17	Yes	Yes	NK	Mutations in trans
			p.(Ser969*)^b			p.(Gly1072Val)
32	H	COL4A4	c.2906C>G	32	No, AR AS, TBMN^9,11,18,19	c.2906C>G	32	No, AR AS, TBMN^9,11,18,19	M	Australian, parents were British	34	28	Yes	Yes	Yes	Confirmed homozygous Parents first cousins
			p.(Ser969*)^b			p.(Ser969*)^b
33	h	COL4A4	c.2906C>G	32	No, AR AS, TBMN^9,11,18,19	c.4538G>A	47	Yes	M	NK	39	22	Yes	Yes	NK
			p.(Ser969*)^b			p.(Cys1513Tyr)
34	h	COL4A4	c.2906C>G	32	No, AR AS, TBMN^9,11,18,19	c.4781_4807dup	47	Yes	F	NK	41	N/A (N @41)	Yes	Yes	NK	Mutations in trans
			p.(Ser969*)^b			p.(Ser1594_Leu1602dup)
35	H	COL4A4	c.2906C>G	32	No, AR AS, TBMN^9,11,18,19	c.2906C>G	32	No, AR AS, TBMN^9,11,18,19	M	NK	36	18	Yes	Yes	NK	Confirmed homozygous
			p.(Ser969*)^b			p.(Ser969*)^b
36	H	COL4A4	c.2906C>G	32	No, AR AS, TBMN^9,11,18,19	c.2906C>G	32	No, AR AS, TBMN^9,11,18,19>	F	NK	35	NK	Yes	Yes	NK	Apparent homozygous
			p.(Ser969*)^b			p.(Ser969*)^b
37	h	COL4A4	c.3602G>A	39	Yes	c.4376G>T	46	Yes	F	English	32	N/A (N @ 30)	Yes	No	NK	Sister has one mutation
			p.(Gly1201Asp)			p.(Gly1459Val)
38	h	COL4A4	c.4200_4201del	44	Yes	c.4522G>A	46	Yes	M	Scottish	46	21	Yes	Yes	Yes	Mutations in trans
			p.(Gly1401fs)^b			p.(Gly1508Ser)
39	h	COL4A4	c.4444dup	46	Yes	c.4763G>A	47	Yes	M	English	29	20	Yes	Yes	NK	Sister has one mutation
			p.(Leu1482fs)^b			p.(Cys1588Tyr)
40	H	COL4A4	c.4788G>A	47	Yes	c.4788G>A	47	Yes	F	NK	17	12	Yes	Yes	NK	Confirmed homozygous– parents are cousins
			p.(Trp1596*)^b			p.(Trp1596*)^b

Sequence nomenclature is based on COL4A3 reference sequence LRG_230 (NM_000091.4) and COL4A4 reference sequence LRG_231 (NM_000092.4), in which nucleotide number 1 corresponds to the first base of the translation initiation codon. AR AS, autosomal recessive Alport syndrome; I, intron; F, female; H, homozygous; h, heterozygous; M, male; N, normal; N/A, not appropriate; NK, not known.

Age when clinically assessed.

A pathogenic mutation resulting in a stop codon (i.e., a nonsense or frameshift mutation).

The mutation was originally identified in Germany (Center for Nephrology and Metabolic Disorders, Germany).