Congenital mirror movements: no mutation in DNAL4 in 17 index cases.

Abstract

Mirror movements are involuntary movements of one side of the body that mirror intentional movements on the opposite side [1]. Affected subjects have a disorganized motor system and are unable to perform purely unimanual movements or skilled dissociated movements of the two hands [2, 3]. Isolated congenital mirror movements (CMM) constitute a rare disorder characterized by mirror movements that persist throughout adulthood, without any additional manifestation. Research on CMM is a fast moving field which has recently gained attention with several breakthroughs in the past few years [2–6]. After DCC and RAD51, implicated in both autosomal dominant CMM and simplex cases [4–6], homozygous mutations in the dynein axonemal light chain 4 gene (DNAL4) were recently reported in a single family with congenital mirror movements (CMM) [7]. DNAL4 is potentially responsible for an autosomal recessive form of the disease, which might suggest its implication in some simplex cases. However, Sanger sequencing of DNAL4 in 2 familial (albeit with autosomal dominant inheritance) and 11 simplex cases did not identify any mutation [7]. These 13 index cases had previously been screened for DCC and RAD51 abnormalities. In the absence of identification of DNAL4 mutations in another family, the implication of this gene in CMM cannot be definitely confirmed. We thus aimed to determine whether DNAL4 mutations may be found in other cases of CMM, particularly in sporadic cases. We previously screened DCC and RAD51 in 26 index cases. No mutation or rearrangement of either of these genes was found in two of six familial cases and 12 of 20 simplex cases [6], and in another family reported previously [5]. We screened the DNAL4 gene in these 15 index cases, and in two novel simplex cases without mutation in either gene (for a total of 3 familial cases with autosomal dominant inheritance and 14 sporadic cases). Sanger sequencing of the coding and flanking intronic regions of DNAL4 was performed using the primers provided by Ahmed et al. [7]. We did not find any variant of DNAL4 in the 17 index cases. Counting the 13 cases screened by Ahmed et al. [7], a total of 30 independent non-DCC non-RAD51 CMM cases have now been tested for DNAL4 mutations, and yet none have been identified, other than in the original family. Although linkage analysis, next generation sequencing and Sanger sequencing did not find another candidate gene in the original family, the possibility of a causative mutation in untranslated, intronic or intergenic regions, as well as A. Meneret (&) O. Trouillard M. Vidailhet C. Depienne E. Roze Inserm, U 1127, 75013 Paris, France e-mail: aurelie.meneret@icm-institute.org