On June 23, Dr. Wei Luo’s team online published a research report entitled “Intronic pentanucleotide TTTCA repeat insertion in SAMD12 gene causes familial cortical myoclonic tremor with epilepsy type 1” on “Brain”.

Familial cortical myoclonic tremor with epilepsy (FCMTE) is an autosomal dominant neurodegenerative disease, characterized by cortical tremor and epileptic seizures. Although four subtypes (type 1-4) mapped on different chromosomes (8q24, 2p11.1-q12.2, 5p15.31-p15.1 and 5p15.31-p15.1) have been reported, the causative gene has not yet been identified. Dr Wei Luo’s team reported the genetic study in a cohort of twenty Chinese pedigrees with FCMTE. Linkage and haplotype analysis in 11 pedigrees revealed maximum two-point LOD scores from 1.64 to 3.77 (LOD scores in 5 pedigrees were > 3.0) in chromosomal region 8q24 and narrowed the candidate region to an interval of 4.9 Mb (Fig.1). Using whole-genome sequencing, long-range PCR and repeat-primed PCR, we identified an intronic pentanucleotide (TTTCA)_n insertion in SAMD12 gene as the cause, which was co-segregated with the disease among the 11 pedigrees mapped on 8q24 and additional 7 un-mapped pedigrees (Fig.2).

This study identified the causative mutation of FCMTE1 for the first time and offered clues for causative mutation identification studies of other monogenetic diseases. This study was supported by the National Natural Science Foundation of China (Proj. No. 81571089, No. 81371266 and No. 81600850).

Web link: https://doi.org/10.1093/brain/awy160

Fig. 1. Pedigree-B linked to FCMTE1 and long-range PCR in some members from Pedigree-B and J.

Fig. 2. Identification of (TTTCA)_n insertion in intron 4 of SAMD12 gene.