ABCMdb

PMID: 16410789

Ringpfeil F, McGuigan K, Fuchsel L, Kozic H, Larralde M, Lebwohl M, Uitto J
Pseudoxanthoma elasticum is a recessive disease characterized by compound heterozygosity.
J Invest Dermatol. 2006 Apr;126(4):782-6., [PubMed]

Sentences

No. Mutations Sentence Comment

28 ABCC6 p.Arg1141* ABCC6 p.Arg1138Trp Five of the alleles harbored the recurrent R1141X mutation, which is prevalent in Caucasian populations, six of the alleles contained the R1138W mutation, and seven alleles harbored the deletion mutation del23-29, all of which have been previously reported in a number of families with PXE (Le Saux et al., 2001; Ringpfeil et al., 2001a; Uitto et al., 2001; Pulkkinen et al., 2002; Chassaing et al., 2004). Login to comment 29 ABCC6 p.Arg1164Gln ABCC6 p.Thr811Met ABCC6 p.Trp218Cys Among the other mutations identified, three were novel missense mutations: W218C, T811M, and R1164Q. Login to comment 30 ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1138Trp ABCC6 p.Arg1138Trp ABCC6 p.Arg1138Trp ABCC6 p.Arg1138Trp ABCC6 p.Arg1138Trp ABCC6 p.Arg1138Trp ABCC6 p.Arg1138Trp ABCC6 p.Arg1138Trp ABCC6 p.Arg1138Trp ABCC6 p.Arg1138Trp ABCC6 p.Phe568Ser ABCC6 p.Arg391Gly ABCC6 p.Arg391Gly ABCC6 p.Arg391Gly ABCC6 p.Arg391Gly ABCC6 p.Trp218Cys ABCC6 p.Trp218Cys ABCC6 p.Trp218Cys ABCC6 p.Trp218Cys ABCC6 p.Trp1324* ABCC6 p.Trp1324* In addition, a previously unpublished nonsense mutation W1324X was F568S/R1141X W1324X/R1141X Family 4 R1138W/R1138W R1138W/R1138W -/R1138W R1138W/- R1138W/- R1138W/- Family 6 R391G/R1138W R391G/R1138W Family 7 Family 2 Del23-29/W218C R391G/W218C Del23-29/W218C Del23-29/R391G W218C/- Del23-29/- Del23-29/- ? Login to comment 31 ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg1141* ABCC6 p.Arg518* ABCC6 p.Arg391Gly ABCC6 p.Arg1164Gln ABCC6 p.Arg1164Gln ABCC6 p.Arg1164Gln ABCC6 p.Arg1164Gln ABCC6 p.Thr811Met R1164Q/R518X R1164Q/R1164Q R1164Q/- -/- Family 5 Del23-29/R391G Del23-29/Del23-29 Family 3 R1141X/del23-29 R1141X/del23-29 Del23-29/- R1141X/T811M Family 1 Figure 1. Login to comment 40 ABCC6 p.Arg1141* In Family 1, the two affected daughters of a clinically unaffected mother and an affected father were compound heterozygotes (R1141X/del23-29), and the parents were carriers of the corresponding mutations. Login to comment 41 ABCC6 p.Arg1141* ABCC6 p.Thr811Met In addition, the father with asymptomatic angioid streaks, evidence of coronary artery disease, history of gastrointestinal bleeding, and positive skin biopsy, but no clinically obvious skin involvement, was compound heterozygous for R1141X and a novel missense mutation T811M. Login to comment 42 ABCC6 p.Arg391Gly ABCC6 p.Trp218Cys ABCC6 p.Trp218Cys In Family 2, the three children were compound heterozygotes with two different combinations (del23-29/W218C and R391G/W218C). Login to comment 43 ABCC6 p.Arg391Gly The mother with minimal clinical signs but with a positive skin biopsy was compound heterozygous for two of these mutations (del23-29/R391G) and manifested with asymptomatic angioid streaks and hypertension. Login to comment 44 ABCC6 p.Trp218Cys However, the father, a heterozygous carrier of the W218C mutation, as well as the maternal grandmother, carrier of the del23-29 mutation, were clinically unaffected. Login to comment 45 ABCC6 p.Arg391Gly In Family 3, the clinically affected son was homozygous for the del23-29 mutation, whereas the mother manifesting with vision loss, intermittent claudication, stroke, and hypertension was a compound heterozygote for del23-29/R391G mutations. Login to comment 48 ABCC6 p.Arg1141* ABCC6 p.Phe568Ser ABCC6 p.Trp1324* In Family 4, the two affected individuals, a father and a son, were compound heterozygotes, both for R1141X mutation in one allele, in combination with either F568S (father) or W1324X (son). Login to comment 49 ABCC6 p.Arg518* ABCC6 p.Arg1164Gln In Family 5, the proband was compound heterozygote for R1164Q/R518X, the missense mutation being inherited from the clinically unaffected father while the nonsense mutation was either a de novo mutation or reflected germline mosaicism in the clinically unaffected mother whose peripheral blood DNA did not carry this mutation. Login to comment 50 ABCC6 p.Arg1164Gln The grandmother of the proband was homozygous for the R1164Q mutation. Login to comment 51 ABCC6 p.Arg1138Trp ABCC6 p.Arg1138Trp ABCC6 p.Arg391Gly Segregation of the mutant alleles in Families 6 and 7 suggested that the homozygosity for the R1138W mutation (Family 6) and compound heterozygosity for the R391G/R1138W mutations (Family 7) in affected individuals in two subsequent generations were due to consanguinity, a conclusion supported by examination of the family pedigrees (see Figure 1) and by haplotype analysis (data not shown). Login to comment 53 ABCC6 p.Arg1141* However, probing the two most common mutations in ABCC6, namely R1141X and deletion of exons 23-29 in 254 control alleles of Caucasian origin, revealed no carriers (data not shown). Login to comment 71 ABCC6 p.Arg391Gly ABCC6 p.Trp218Cys It is of interest that in Family 2, the eldest son and the daughter had a clearcut clinical diagnosis of PXE, yet the second son, upon examination by a dermatologist and an ophthalmologist, showed no clinical evidence of PXE at the age of 37 years even though he was compound heterozygous for R391G/W218C mutations. Login to comment