Czech family confirms the link between FBLN5 and Charcot–Marie–Tooth type 1 neuropathy

Abstract

Sir, The article by Auer-Grumbach et al. (2011) reporting that fibulin 5 ( FBLN5 ) mutations are also linked to inherited neuropathies helped us to clarify the cause of autosomal dominant, demyelinating hereditary motor and sensory neuropathy (HMSN I) in our long-time known, but unsolved, Czech family. Before this study was published, mutations in FBLN5 were associated only with the connective tissue disorder cutis laxa (Loeys et al. , 2002; Markova et al. , 2003; Lotery et al. , 2006; Nascimento et al. , 2010) and age-related macular degeneration leading to vision loss in those aged >50 years (Stone et al. , 2004; Lotery et al. , 2006). Auer-Grumbach et al. (2011) were the first to describe a large family with demyelinating Charcot–Marie–Tooth (CMT1) and linkage with the interval on chromosome 14. Subsequent resequencing of this region revealed only one novel variant c.1117 C > T (p.R373C) segregating with the disease in the family. Additional screening of 112 patients with Charcot–Marie–Tooth disease showed two other sequence variations in two patients with pure motor neuropathy and hyperelastic skin. The linkage with log of odds score >3.31 indicates the FBLN5 mutation as highly probably causal for HMSN I, but no functional study to confirm this was performed, and no other study on FBLN5 mutations in a family with HMSN has been published to date. This Austrian HMSN I family is the only one reported worldwide. We report a second family with non-syndromic inherited demyelinating motor and sensory neuropathy (HMSN I) with FBLN5 mutation and confirm FBLN5 mutations as the new cause of HMSN I. We used exome sequencing for clarification of the cause of HMSN I in a Czech family recruited in 2001 (Fig. 1A). The most frequent causes of CMT1 (CMT1 duplication/HNPP …