Mutation Details

DNA changeProtein changeExon/intronTypeReported classificationBatemanSIFTPolyPhenConservedProtein domainRemarksLOVD ID
c.925G>Ap.Glu309LysExon 8MissenseDisease-causingSurface siteNot toleratedBenignModerately Ig 3 Reduces heterophilic binding; having normal homophilic binding (De Angelis). Mutation segregates with disease. Defective in stimulating human epidermal growth factor receptor tyrosine kinase activity in vitro (Nagaraj)

Patients

Family# Affected relativesClinical featuresRemarksReference
1 6 Adducted thumbs, Aphasia, Hydrocephalus, Mental retardation, Spastic paraplegia   Jouet et al. (1995a)
2 2 Adducted thumbs, Mental retardation, Spastic paraplegia   Straussberg et al. (1991)

References

YearAuthorTitleJournalVolumePagesWeblink
2004Cheng and LemmonPathological missense mutations of neural cell adhesion molecule L1 affect neurite outgrowth and branching on an L1 substrate Mol. Cell. Neurosci. 27522-530 15555929
1999De Angelis et al.Pathological missense mutations of neural cell adhesion molecule L1 affect homophilic and heterophilic binding activities. EMBO J. 18 No. 174744-4453 10469653
2002De Angelis et al.Disease-associated mutations in L1 CAM interfere with ligand interactions and cell-surface expression Hum. Mol. Genet. 111-12 11772994
1997Fransen et al.L1-associated diseases: clinical geneticists divide, molecular geneticists unite Hum. Mol. Genet. 61625-1632 9300653
1995aJouet et al.New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome Am. J. Hum. Genet. 561304-1314 7762552
2000Kenwrick et al.Neural cell recognition molecule L1: relating biological complexity to human disease mutations Hum. Mol. Genet. 9879-886 10767310
2009Nagaraj et al.Pathogenic human L1-CAM mutations reduce the adhesion-dependent activation of EGFR Hum. Mol. Genet. 18 (20)3822-3831 19617634
1991Straussberg et al.X-linked mental retardation with bilateral clasped thumbs: report of another affected family Clin. Genet. 40337-341 1756607