Molecular characterisation of SGCE-associated myoclonus-dystonia ...

Results 47
showed characteristic clinical features of definite M-D (7 female). Fifteen individuals were
diagnosed as probable M-D cases (7 female), and ten patients as possibly affected (5 female).
Age of onset was not significantly different in these three groups (p>0.05; independent t-test
with unequal sample size). Only when comparing mutation carriers (mean age of onset: 3.5+/-
3.9 years) and non-mutation carriers (mean age of onset: 11.5+/-10.1 years), a significant
difference was found (p=0.027; independent t-test with unequal sample size). Demographic,
clinical, genetic information and additional features are summarized in Table 5. Selected
special features are detailed below:
In the mutation-positive families, paternal transmission of the disease prevailed (Table 5).
However, in the family of IP15251, the mode of transmission was compatible with paternal
expression with the exception of one affected female (V:7) who inherited the disorder from
her mother (Fig 8D). Though, a transmission of the disease through individual III:1 and the
patient’s father (IV:1) can not be excluded in this case.
Two patients carried large deletions, including the entire SGCE gene and the collagen type I
alpha 2 gene (COL1A2). In both families, additional phenotypes were observed beyond the
motor syndrome. IP16535 had delayed skeletal development and later presented with severe
generalized osteoporosis, necrosis of the femoral head, and cartilage defects of the condyli
leading to hip and knee replacement in his twenties. There were no abnormalities of the skin
and eyes. Neither of his mutation-negative parents showed any signs of bone and joint
disease. The four-year old index patient IP15916 had no other features, however, two
mutation carriers including the patient’s father, as well as at least three other obligate
mutation carriers, reported joint problems (Fig 8A). More detailed information was
unavailable for these family members.