what-when-how
In Depth Tutorials and Information
TABLE 23.1
Clinical and molecular findings in Patients Diagnosed with the Arthrochalasis Type of Ehlers-Danlos Syndrome
(Continued)
Congenital
Bilateral Hip
Dislocation
Family
History*
Case
Sex
Scoliosis
Additional Findings
Gene
Mutation
References
25
m
+
−
?
−
COL1A2
c.279+1G
>
T
Intron 6 +1G
>
T
28
26
f
+
+
?
−
COL1A2
c.279+1G
>
C
Intron 6 +1G
>
C
28
27
f
+
−
Fractures
−
COL1A1
c.392_543+8delinsT
genomic deletion between
exon 5 and intron 6
22
28
?
+
−
COL1A1
c.472−2A
>
G
Intron 5
−
2A>G
29
29
f
+
EDS VII C-like features
−
COL1A1
c.472−1G
>
A
Intron 5
−
1G>A
7
30
m
+
+
Fractures, Wormian bones,
dentinogenesis imperfecta
−
COL1A1
c.472−1G
>
A
Intron 5
−
1G>A
22
31
+
−
COL1A1
c.472−1G
>
C
Intron 5
−
1G>C
29
32
m
+
?
Fractures, osteopenia,
dentinogenesis imperfecta,
Wormian bones, rectum prolapse
−
COL1A1
c.472−1G
>
T
Intron 5
−
1G>T
30
33
f
Fractures
COL1A1
c.543G>A
Exon 6
−
1G>A
31
+
+
−
34
f
Fractures
COL1A1
c.543G>A
Exon 6 −1G>A
17,32-34
+
+
−
35
?
COL1A1
c.543G>A
Exon 6 −1G>C
29
+
−
36
f
+
?
?
+ 3 cases in
2 generations
COL1A1
c.478G>C
28 (and personal
communication
E. Reinstein)
37
f
+
−
COL1A1
c.472-2A
>
T
Intron 5 −2A>T
35
38 §
f
+
?
5,6,36
39 §
f
+
−
4-6,36
40 §
m
+
normal
COL1A1
and
COL1A2
unpublished
41 §
f
?
6
42 §
m
?
6
43 §
f
?
6
The symbols designate positive (
+
), negative (
−
) or questionable (?) findings; empty boxes denote unknown or not described features; the symbol (
±
) refers to possible parental
mosaicism; (§) denotes normal structure of collagen produced by cultured fibroblasts as judged by SDS-polyacrylamide gel electrophoresis.
for proteinases (for example, pepsin and α-chymotrypsin)
and the first triplet of the main helical Gly-X-Y domain.
The loss of the N-proteinase cleavage site causes the reten-
tion of the N-propeptide in the mature α1(I) and α2(I) mol-
ecules, which are referred to as pNα1(I)- and pNα2(I)-like
chains, respectively (see
Figure 23.4
).
In two patients with EDS VIIB (Cases 3
10
and 4 own
unpublished) a G-to-C change at the splice accep-
tor site of intron 5 activates a cryptic splice site in exon
6, removing five amino acid residues including the
N-proteinase cleavage site, but preserving the crosslink-
ing lysine residue. Both mother and son, and father and
daughter, respectively, were affected with typical EDS VII.
Analysis by SDS-polyacrylamide gel electrophore-
sis (SDS-PAGE) of pepsin-digested collagens produced
by fibroblasts of EDS VIIA and VIIB patients reveals,
in addition to the normal α1(I) and the α2(I) chains, the
presence of mutant pNα1(I)- and pNα2(I)-like chains,
