Abstract
X-linked hydrocephalus is a genetic form of hydrocephalus that frequently occurs in males. It is characterized by ventricular dilatation, mental retardation, deformity of the thumb and spastic paraparesis. Recently, 23 different mutations of the gene for the neural cell adhesion molecule, L1CAM, located at chromosome region Xq28, have been reported, 16 of which were detected in families with X-linked hydrocephalus. We sequenced the coding region of the L1CAM gene of patients from two different families with X-linked hydrocephalus and found a novel mutation at nucleotide residue 1963 in one family. This mutation from adenine to guanine results in an amino acid change from lysine to glutamic acid at residue 655 of the L1CAM protein, which belongs to the fibronectin type III domain. We report another method for the rapid identification of the mutation based on the polymerase chain reaction. This mutation was not detected among 70 X chromosomes from a healthy population. Ours is the first report demonstrating this gene mutation in X-linked hydrocephalus in an Asian population. Our findings further emphasize the evolving genotypic heterogeneity in X-linked hydrocephalus.
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Appel F, Holm J, Conscience JF, Schachner M (1993) Several extracellular domains of the neural cell adhesion molecule L1 are involved in neurite outgrowth and cell body adhesion. J Neurosci 13:4764–4775
Asou H, Miura M, Kobayashi M, Uyemura K, Itoh K (1992) Cell adhesion molecule L1 guides cell migration in primary reaggregation cultures of mouse cerebellar cells. Neurosci Lett 144:221–224
Coucke P, Vits L, Van Camp G, Serville F, Lyonnet S, Kenwrick S, Rosenthal A, Wehnert M Munnich A, Willems P (1994) Identification of a 5′ splice site mutation in intron 4 of the L1CAM gene in an X-linked hydrocephalus family. Hum Mol Genet 3:671–673
Fransen E, Schrander-Stumpel C, Vits L, Coucke P, Van Camp G, Willems P (1994) X-linked hydrocephalus and MASA syndròme present in one family are due to a single missense mutation in exon 28 of the L1CAM gene. Hum Mol Genet 3:2255–2256
Hlavin ML, Lemmon V (1991) Molecular structure and functional testing of human L1CAM: an interspecies comparison. Genomics 11:416–423
Izumoto S, Younger D, Hays AP, Martone RL, Smith RT, Herbert J (1992) Familial amyloidotic polyneuropathy presenting with carpal tunnel syndrome and a new transthyretin mutation, asparagine 70. Neurology 42:2094–2102
Jouet M, Kenwrick S (1995) Gene analysis of L1 neural cell adhesion molecule in prenatal diagnosis of hydrocephalus. Lancet 345:161–162
Jouet M, Rosenthal A, MacFarlane J, Kenwrick S (1993) A missense mutation confirms the L1 defect in X-linked hydrocephalus (HSAS). Nat Genet 4:331
Jouet M, Rosenthal A, Armstrong G, MacFarlane J, Stevenson R, Paterson J, Metzenberg A, Ionasescu V, Temple K, Kenwrick S (1994) X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene. Nat Genet 7:402–407
Jouet M, Moncla A, Paterson J, McKeown C, Fryer A, Carpenter N, Holmberg E, Wadelius C, Kenwrick S (1995) New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome. Am J Hum Genet 56:1304–1314
Lemmon V, Farr KL, Lagenaur C (1989) L1-mediated axon outgrowth occurs via a homophilic binding mechanism. Neuron 2:1597–1603
Moos M, Tracke R, Scherer H, Teplow D, Fruh K, Schachner M (1988) Neural adhesion molecule L1 as a member of the immunoglobulin superfamily with binding domains similar to fibronectin. Nature 334:701–703
Reid RA, Hemperly JJ (1992) Variants of human L1 cell adhesion molecule arise through alternate splicing of RNA. J Mol Neurosci 3:127–135
Rosenthal A, Joulet M, Kenwrick S (1992) Aberrant splicing of neural cell adhesion molecule L1 mRNA in a family with X-linked hydrocephalus. Nat Genet 2:107–112
Strain L, Gosden CM, Brock DJH, Bonthron DT (1994) Genetic heterogeneity in X-linked hydrocephalus: linkage to markers within Xq27.3. Am J Hum Genet 54:236–243
Van Camp G, Vits L, Coucke P, Lyonnet S, Schrander-Stumpel C, Darby J, Holden J, Munnich A, Willems P (1993) A duplication in the L1CAM gene associated with X-linked hydrocephalus. Nat Genet 4:421–425
Vits L, Van Camp G, Coucke P, Fransen E, De Boulle K, Reyniers E, Korn B, Poustka A, Wilson G, Schrander-Stumpel C, Winter RM, Schwartz C, Willems PJ (1994) MASA syndrome is due to mutations in the neural cell adhesion gene L1CAM. Nat Genet 7:408–412
Willems PJ, Vits L, Raeymaekers P, Beuten J, Coucke P, Holden JJA, Van Broeckhoven C, Warren ST, Sagi M, Robinson D, Dennis N, Friedman KJ, Magnay D, Lyonnet S, White BN, Wittwe BH, Aylsworth AS, Reicke S (1992) Further localization of X-linked hydrocephalus in the chromosomal region Xq28. Am J Hum Genet 51:307–315
Wong EV, Kenwrick S, Willems P, Lemmon V (1995) Mutations in the cell adhesion molecule L1 cause mental retardation. Trends Neurosci 18:168–172
Yamasaki M, Arita N, Hiraga S, Izumoto S, Morimoto K, Hayakawa T (1995) X-linked hydrocephalus in Japan. Clinical and neuroradiological study. J Neurosurg 83:50–55
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Izumoto, S., Yamasaki, M., Arita, N. et al. A new mutation of the L1CAM gene in an X-linked hydrocephalus family. Child's Nerv Syst 12, 742–747 (1996). https://doi.org/10.1007/BF00261591
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DOI: https://doi.org/10.1007/BF00261591