GENES journal published an article by FSBI RCMG researchers
A Family Case of Congenital Myasthenic Syndrome-22 Induced by Different Combinations of Molecular Causes in Siblings.
Shchagina, O.; Bessonova, L.; Bychkov, I.; Beskorovainaya, T.; Poliakov, A.
The article describes a family case of a rare recessive disorder. Congenital myasthenic syndrome-22 (CMS22, OMIM 616224) is a very rare recessive hereditary disorder. Today, ten CMS22 patients have been found. Their disorder was caused by 10 different Loss-of-Function mutations and 6 gross deletions in the PREPL gene. For the first time in the world, the article describes the missense variant as the cause of congenital myasthenic syndrome. It was shown that the c.2094G> T variant, simultaneously with p.Lys698Asn amino acid substitution, affects splicing, leading to exon 14 skipping in mRNA.
The cause of the proband's disorder is a compound heterozygous state of two previously non-described pathogenic PREPL variants: a c.1528C>T (p.(Arg510Ter)) nonsense mutation and a c.2094G>T pseudo-missense variant, which, simultaneously with a p.(Lys698Asn) amino acid substitution, affects splicing, leading to exon 14 skipping in mRNA. The second sibling's disorder was caused by a homozygous nonsense c.1528C>T (p.(Arg510Ter)) mutation due to maternal uniparental disomy (UPD) of chromosome 2.
Genes 2020, 11, 821. doi.org/10.3390/genes11070821)