Preimplantation genetic diagnosis of spinal muscular atrophy |
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Authors: | Dreesen JC; Bras M; de Die-Smulders C; Dumoulin JC; Cobben JM; Evers JL; Smeets HJ; Geraedts JP |
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Institution: | Department of Molecular Cell Biology & Genetics, Maastricht University, The Netherlands. |
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Abstract: | After Duchenne muscular dystrophy, spinal muscular atrophy (SMA) is the
most common severe neuromuscular disease in childhood. Since 1995,
homozygous deletions in exon 7 of the survival motor neuron (SMN) gene have
been described in >90-95% of SMA patients. However, the presence of a
highly homologous SMN copy gene complicates the detection of exon 7
deletions. This paper describes the adjustment and evaluation of an
established SMN exon 7 polymerase chain reaction (PCR) protocol at the
single cell level, and the first preimplantation genetic diagnosis (PGD) of
SMA with this PCR protocol. To determine PCR efficiency and allelic loss,
200 leukocytes of normal individuals, SMA carriers and patients, and 25
blastomeres were tested. The PCR efficiency of the SMN exon 7 and the
adjacent copy gene sequence, tested in the leukocytes, were 90% and 91%
respectively. No allelic loss was detected. One out of 25 blastomeres
tested revealed a negative PCR signal for the SMN exon 7 sequence. All 25
showed the copy gene sequence. PGD of SMA was offered to a couple with an
affected child homozygous for the SMN exon 7 deletion. After
intracytoplasmic sperm injection, four and five embryos could be genotyped
for the SMN exon 7 in two cycles respectively. After embryo transfer in the
second PGD cycle an ongoing gemelli pregnancy was achieved. This study
demonstrates that PGD for SMA is feasible when a previous child is
homozygous for the SMN exon 7 deletion.
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