Figure 2.

Mutations Found in LTBP4

(A) The parents of patient 1 were second cousins.

(B) DNA sequencing showed that patient 1 (V.1) was homozygous for mutation p.Q1185fsX1211, whereas his unaffected father (Fa) and mother (Mo) were both heterozygous.

(C) The parents of patient 2 were unaffected and unrelated.

(D) Patient 2 (II.1) was compound heterozygous for mutation p.P264fsX300 inherited from his mother (Mo) and mutation p.C857X inherited from his father (Fa).

(E) Patient 3 was an offspring of first-cousin parents.

(F) Homozygous mutation p.C274G (arrowhead) in patient 3 (IV.1) compared to normal sequence in a control individual (Co).

(G) The pedigree of patient 4.

(H) Patient 4 (II.1) was compound heterozygous for mutations p.C857X and p.P1376fsX1403. Neither of these mutations was found in his mother (Mo), suggesting that at least one of the mutations was de novo. No DNA sample was available from the father.

(I) The cysteine residue replaced by the mutation p.C274G found in patient 3 is highly conserved in all vertebrates.

(J) Schematic representation of the domain structure of LTBP4, showing the location of the mutations.