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

Results 54
3.1.4 Qualitative mutational screening
Six out of 35 (17.1%) index patients had either a point mutation (5 cases) or a small deletion
(1 case) in the SGCE gene (four of these mutation-positive cases showed definite signs of M-
D). One of the identified mutations was novel. This two base pair deletion in exon 6 induced a
premature stop at codon 258 (c.771_772delAT, p.C258X).
The remaining mutations had been previously described and are also predicted to prevent the
synthesis of a full-length protein: Three index patients (IP1601, IP15251 and IP2625) carried
disease-causing sequence changes in exon 3 (c.289C>T, p.R97X and twice c.304C>T;
p.R102X). A one base pair substitution was detected in exon 6 (c.709C>T; p.R237X in
IP15039). In the last patient (IP2141), a nonsense mutation in exon 9 (c.1114C>T, p.R372X)
was found.
3.1.5 Review of mutations in SGCE
Out of 51 publications, available on PubMed, 28 are reviewed here (see also 2.3.14). Taken
together, 107 mutation-positive M-D cases have been described. For these patients, 64
sequence changes in SGCE were identified, including 15 recurrent mutations (Fig 11). In 37%
(40/107) of the above-mentioned individuals a single nucleotide change led to a truncation of
SGCE. With 33% (35/107), deletions were the second most frequent mutational cause of M-
D. Among the 35 known deletions, ten are gene dosage alterations encompassing whole
exons. Those account for 9% (10/107) of all cases with known mutations in SGCE. In
addition to that, 12 (out of 107) patients with missense mutations (11%), 17 with splice site
alterations (16%) and three individuals with insertions (3%) have been identified yet. The
mutation detected with the highest frequency is a cytosine to thymine change at cDNA
position 304 which leads to a premature stopcodon at AA position 102.