An updated and upgradedL1CAMmutation database

Abstract

ABSTRACT:The L1 syndrome is an X-linked recessive disease caused by mutations in the L1CAM gene. To date more than 200 different mutations have been reported, scattered over the entire gene, about 35% being missense mutations. Although it is tempting to consider these missense mutations as being disease-causing, one should be careful in drawing any firm conclusions, unless there is additional supporting information. This is in contrast to truncating mutations, which are always considered to be disease-causing, unless they involve truncations close to the gene stop codon. In order to allow conclusions to be drawn on the disease-causing nature of L1CAM (missense) mutations, we have updated and upgraded our LICAM mutation database with more pathogenicity data and clinical information collected from the literature or generated by our own research. As a result, the renewed database offers condensed scientific information, allowing conclusions to be drawn on the pathogenicity and severity of LICAM mutations based on multiple factors. The L1CAM Mutation Database is at: www.l1cammutationdatabase.info.

Three cases with L1 syndrome and two novel mutations in the L1CAM gene

“…Over 270 different disease-causing mutations of the L1CAM gene have been reported to date [11]. Several authors have described a correlation between the type of mutation and the severity of the syndrome [3,10,12].…”

Pathomechanistic characterization of two exonic L1CAM variants located in trans in an obligate carrier of X-linked hydrocephalus

“…Error bars represent SEM from four independent experiments. Statistical significance, *p00.021; Student's t test (two tailed, unpaired) L1 syndrome [4,42]. However, it is important to differentiate whether a cysteine substitution affects a structurally important key residue or an amino acid residue exposed at the protein surface, as for example the human pathogenic Y1070C mutation of the fifth FnIII domain of L1CAM.…”

“…To date more than 200 different L1CAM mutations have been detected, and about one third of them are missense mutations [4]. The majority of these missense mutations affect extracellular domains of L1CAM, and several of them have been shown to impair intracellular trafficking and thus cell surface expression of L1CAM [8][9][10][11][12].…”

“…Mutations in the L1CAM gene cause a spectrum of neurological disorders with an X-linked recessive mode of inheritance [4][5][6][7]. These disorders comprise HSAS (X-linked hydrocephalus with aqueductal stenosis; OMIM 307000), MASA syndrome (Mental retardation, Aphasia, Shuffling gait, Adducted thumbs; OMIM 303350), and X-linked complicated corpus callosum agenesis (OMIM 304100), which have been collectively referred to as L1 syndrome.…”

Role of L1CAM for axon sprouting and branching

“…The important role of L1CAM in the developing nervous system is further emphasized by more than 200 human gene mutations that cause a variety of neurological disorders referred to as L1 syndrome (Jouet et al 1995;Kanemura et al 2006;Schäfer and Altevogt 2010;Vos and Hofstra 2010). The broad clinical spectrum includes X-linked hydrocephalus, hypoplasia of the corticospinal tract, corpus callosum agenesis and mental retardation (Rosenthal et al 1992;Jouet et al 1993Jouet et al , 1994Fransen et al 1996).…”