G2Cdb::Human Disease report

Disease id
D00000176
Name
MASA syndrome
Nervous system disease
yes

Genes (1)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00001881 L1CAM
L1 cell adhesion molecule
Y (7562969) Unknown (?) Y
G00001881 L1CAM
L1 cell adhesion molecule
Y (7762552) Unknown (?) Y
G00001881 L1CAM
L1 cell adhesion molecule
Y (7881431) Microinsertion (MI) Y
G00001881 L1CAM
L1 cell adhesion molecule
Y (7920659) Deletion (D) Y
G00001881 L1CAM
L1 cell adhesion molecule
Y (7920659) Microinsertion (MI) Y
G00001881 L1CAM
L1 cell adhesion molecule
Y (7920660) Deletion (D) Y
G00001881 L1CAM
L1 cell adhesion molecule
Y (7920660) Single nucleotide polymorphism (SNP) Y
G00001881 L1CAM
L1 cell adhesion molecule
Y (9521424) Splice site mutation (SpS) Y
G00001881 L1CAM
L1 cell adhesion molecule
Y (9521424) Microinsertion (MI) Y
G00001881 L1CAM
L1 cell adhesion molecule
Y (9744477) Microinsertion (MI) Y
G00001881 L1CAM
L1 cell adhesion molecule
Y (9744477) Nonsense (No) Y
G00001881 L1CAM
L1 cell adhesion molecule
Y (9744477) Deletion (D) Y
G00001881 L1CAM
L1 cell adhesion molecule
Y (9744477) Splice site mutation (SpS) Y

References

  • Identification of novel L1CAM mutations using fluorescence-assisted mismatch analysis.

    Saugier-Veber P, Martin C, Le Meur N, Lyonnet S, Munnich A, David A, Hénocq A, Héron D, Jonveaux P, Odent S, Manouvrier S, Moncla A, Morichon N, Philip N, Satge D, Tosi M and Frébourg T

    Laboratoire de Génétique Moléculaire, CHU de Rouen, France.

    The L1CAM gene, which is located in Xq28 and codes for a neuronal cell adhesion molecule, is involved in three distinct conditions: HSAS (hydrocephalus-stenosis of the aqueduct of Sylvius), MASA (mental retardation, aphasia, shuffling gait, adductus thumbs), and SPG1 (spastic paraplegia). Molecular analysis of the L1CAM gene is labor-intensive because of the size of the coding region, which is fragmented in numerous exons, and because of the great allelic heterogeneity and distribution of the mutations. The FAMA (fluorescent assisted mismatch analysis) method combines the excellent sensitivity of the chemical cleavage method for scanning PCR fragments larger than 1 kb and the power of automated DNA sequencers. In order to optimize this method for L1CAM, we divided the gene into nine genomic fragments, each including three to four exons. These fragments were PCR-amplified using nine sets of primers containing additional rare universal sequences. A second-stage PCR, per formed with the two dye-labeled universal primers, allowed us to generate 1-kb-labeled fragments, which were then submitted to the chemical cleavage analysis. Among 12 French families with HSAS and/or MASA, we identified nine distinct L1CAM mutations, seven of which were novel, and an intronic variation. This study demonstrates that FAMA allows rapid and reliable detection of mutations in the L1CAM gene and thus represents one of the most appropriate methods to provide diagnosis for accurate genetic counseling in families with HSAS, MASA, or SPG1.

    Human mutation 1998;12;4;259-66

  • Multiple exon screening using restriction endonuclease fingerprinting (REF): detection of six novel mutations in the L1 cell adhesion molecule (L1CAM) gene.

    Du YZ, Srivastava AK and Schwartz CE

    J.C. Self Research Institute of Human Genetics, Greenwood Genetic Center, South Carolina 29646, USA.

    Restriction endonuclease fingerprinting (REF) has been utilized to screen 19 of the 28 exons in the L1CAM gene using only 5 PCR reactions. The clustered exons were amplified and the PCR products were subjected to endonuclease digestion and subsequent gel electrophoresis to produce a highly informative fingerprint for each PCR product. An alteration in the fingerprint, when compared to a control, determined the specific DNA fragment containing the mutation. Sequencing of the corresponding exon and flanking region was done to determine the precise location of the mutation. Using this method we have identified 6 novel mutations in the L1CAM gene in 5 patients with X-linked hydrocephalus and 2 patients with MASA. One of the mutations was common to both a patient with HSAS and a patient with MASA. The utilization of REF will allow for easier and quicker detection of mutations in the L1CAM gene. This method should be applicable for screening other genes with multiple, clustered exons.

    Human mutation 1998;11;3;222-30

  • Mutations in L1-CAM in two families with X linked complicated spastic paraplegia, MASA syndrome, and HSAS.

    Ruiz JC, Cuppens H, Legius E, Fryns JP, Glover T, Marynen P and Cassiman JJ

    Centre for Human Genetics, University of Leuven, Belgium.

    The suggestion that the three X linked syndromes X linked spastic paraplegia (MIM 312900), MASA syndrome (MIM 303350), and X linked hydrocephalus owing to stenosis of the aqueduct of Sylvius (MIM 307000) are variable clinical manifestations of mutations at the same locus at Xq28 was confirmed by the finding of mutations in the L1-CAM gene in the three syndromes. Recently, two families in which different subjects showed a clearly different phenotype within the same family of the three X linked syndromes were described. A reverse transcription PCR assay was developed for the analysis of the L1-CAM cDNA in two of the members of these families. RNA isolated from EBV transformed cell lines and a colon carcinoma derived cell line was used as a starting material. The L1-CAM cDNA of two male patients from each family was sequenced. We report two new mutations in the L1-CAM gene in these two families showing that the three different phenotypes observed in different generations within the same family are variable phenotypic expressions of the same mutation.

    Journal of medical genetics 1995;32;7;549-52

  • New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome.

    Jouet M, Moncla A, Paterson J, McKeown C, Fryer A, Carpenter N, Holmberg E, Wadelius C and Kenwrick S

    University of Cambridge Department of Medicine, Addenbrooke's Hospital, United Kingdom.

    The neural cell-adhesion molecule L1 is involved in intercellular recognition and neuronal migration in the CNS. Recently, we have shown that mutations in the gene encoding L1 are responsible for three related disorders; X-linked hydrocephalus, MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs) syndrome, and spastic paraplegia type I (SPG1). These three disorders represent a clinical spectrum that varies not only between families but sometimes also within families. To date, 14 independent L1 mutations have been reported and shown to be disease causing. Here we report nine novel L1 mutations in X-linked hydrocephalus and MASA-syndrome families, including the first examples of mutations affecting the fibronectin type III domains of the molecule. They are discussed in relation both to phenotypes and to the insights that they provide into L1 function.

    American journal of human genetics 1995;56;6;1304-14

  • X-linked hydrocephalus and MASA syndrome present in one family are due to a single missense mutation in exon 28 of the L1CAM gene.

    Fransen E, Schrander-Stumpel C, Vits L, Coucke P, Van Camp G and Willems PJ

    Department of Medical Genetics, University of Antwerp-UIA, Belgium.

    Human molecular genetics 1994;3;12;2255-6

  • MASA syndrome is due to mutations in the neural cell adhesion gene L1CAM.

    Vits L, Van Camp G, Coucke P, Fransen E, De Boulle K, Reyniers E, Korn B, Poustka A, Wilson G, Schrander-Stumpel C et al.

    Department of Medical Genetics, University of Antwerp, Belgium.

    MASA syndrome is a recessive X-linked disorder characterized by mental retardation, adducted thumbs, shuffling gait, aphasia and, in some cases, hydrocephalus. Since it has been shown that X-linked hydrocephalus can be caused by mutations in L1CAM, a neuronal cell adhesion molecule, we performed an L1CAM mutation analysis in eight unrelated patients with MASA syndrome. Three different L1CAM mutations were identified: a deletion removing part of the open reading frame and two point mutations resulting in amino acid substitutions. L1CAM, therefore, harbours mutations leading to either MASA syndrome or HSAS, and might be frequently implicated in X-linked mental retardation with or without hydrocephalus.

    Nature genetics 1994;7;3;408-13

  • X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene.

    Jouet M, Rosenthal A, Armstrong G, MacFarlane J, Stevenson R, Paterson J, Metzenberg A, Ionasescu V, Temple K and Kenwrick S

    Department of Medicine, University of Cambridge, Addenbrooke's Hospital, UK.

    X-linked hydrocephalus, spastic paraplegia type I and MASA syndrome are related disorders with loci in subchromosomal region Xq28. We have previously shown that X-linked hydrocephalus is caused by mutations in the gene for neural cell adhesion molecule L1 (L1CAM), an axonal glycoprotein involved in neuronal migration and differentiation. Here we report mutations of the L1 gene in MASA syndrome and SPG1, in addition to HSAS families. Two of the HSAS mutations would abolish cell surface expression of L1 and represent the first functional null mutations in this disorder. Our results indicate that these three syndromes from part of a clinical spectrum resulting from a heterogeneous group of mutations in the L1 gene.

    Nature genetics 1994;7;3;402-7

Literature (7)

Pubmed - other

  • Identification of novel L1CAM mutations using fluorescence-assisted mismatch analysis.

    Saugier-Veber P, Martin C, Le Meur N, Lyonnet S, Munnich A, David A, Hénocq A, Héron D, Jonveaux P, Odent S, Manouvrier S, Moncla A, Morichon N, Philip N, Satge D, Tosi M and Frébourg T

    Laboratoire de Génétique Moléculaire, CHU de Rouen, France.

    The L1CAM gene, which is located in Xq28 and codes for a neuronal cell adhesion molecule, is involved in three distinct conditions: HSAS (hydrocephalus-stenosis of the aqueduct of Sylvius), MASA (mental retardation, aphasia, shuffling gait, adductus thumbs), and SPG1 (spastic paraplegia). Molecular analysis of the L1CAM gene is labor-intensive because of the size of the coding region, which is fragmented in numerous exons, and because of the great allelic heterogeneity and distribution of the mutations. The FAMA (fluorescent assisted mismatch analysis) method combines the excellent sensitivity of the chemical cleavage method for scanning PCR fragments larger than 1 kb and the power of automated DNA sequencers. In order to optimize this method for L1CAM, we divided the gene into nine genomic fragments, each including three to four exons. These fragments were PCR-amplified using nine sets of primers containing additional rare universal sequences. A second-stage PCR, per formed with the two dye-labeled universal primers, allowed us to generate 1-kb-labeled fragments, which were then submitted to the chemical cleavage analysis. Among 12 French families with HSAS and/or MASA, we identified nine distinct L1CAM mutations, seven of which were novel, and an intronic variation. This study demonstrates that FAMA allows rapid and reliable detection of mutations in the L1CAM gene and thus represents one of the most appropriate methods to provide diagnosis for accurate genetic counseling in families with HSAS, MASA, or SPG1.

    Human mutation 1998;12;4;259-66

  • Multiple exon screening using restriction endonuclease fingerprinting (REF): detection of six novel mutations in the L1 cell adhesion molecule (L1CAM) gene.

    Du YZ, Srivastava AK and Schwartz CE

    J.C. Self Research Institute of Human Genetics, Greenwood Genetic Center, South Carolina 29646, USA.

    Restriction endonuclease fingerprinting (REF) has been utilized to screen 19 of the 28 exons in the L1CAM gene using only 5 PCR reactions. The clustered exons were amplified and the PCR products were subjected to endonuclease digestion and subsequent gel electrophoresis to produce a highly informative fingerprint for each PCR product. An alteration in the fingerprint, when compared to a control, determined the specific DNA fragment containing the mutation. Sequencing of the corresponding exon and flanking region was done to determine the precise location of the mutation. Using this method we have identified 6 novel mutations in the L1CAM gene in 5 patients with X-linked hydrocephalus and 2 patients with MASA. One of the mutations was common to both a patient with HSAS and a patient with MASA. The utilization of REF will allow for easier and quicker detection of mutations in the L1CAM gene. This method should be applicable for screening other genes with multiple, clustered exons.

    Human mutation 1998;11;3;222-30

  • Mutations in L1-CAM in two families with X linked complicated spastic paraplegia, MASA syndrome, and HSAS.

    Ruiz JC, Cuppens H, Legius E, Fryns JP, Glover T, Marynen P and Cassiman JJ

    Centre for Human Genetics, University of Leuven, Belgium.

    The suggestion that the three X linked syndromes X linked spastic paraplegia (MIM 312900), MASA syndrome (MIM 303350), and X linked hydrocephalus owing to stenosis of the aqueduct of Sylvius (MIM 307000) are variable clinical manifestations of mutations at the same locus at Xq28 was confirmed by the finding of mutations in the L1-CAM gene in the three syndromes. Recently, two families in which different subjects showed a clearly different phenotype within the same family of the three X linked syndromes were described. A reverse transcription PCR assay was developed for the analysis of the L1-CAM cDNA in two of the members of these families. RNA isolated from EBV transformed cell lines and a colon carcinoma derived cell line was used as a starting material. The L1-CAM cDNA of two male patients from each family was sequenced. We report two new mutations in the L1-CAM gene in these two families showing that the three different phenotypes observed in different generations within the same family are variable phenotypic expressions of the same mutation.

    Journal of medical genetics 1995;32;7;549-52

  • New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome.

    Jouet M, Moncla A, Paterson J, McKeown C, Fryer A, Carpenter N, Holmberg E, Wadelius C and Kenwrick S

    University of Cambridge Department of Medicine, Addenbrooke's Hospital, United Kingdom.

    The neural cell-adhesion molecule L1 is involved in intercellular recognition and neuronal migration in the CNS. Recently, we have shown that mutations in the gene encoding L1 are responsible for three related disorders; X-linked hydrocephalus, MASA (mental retardation, aphasia, shuffling gait, and adducted thumbs) syndrome, and spastic paraplegia type I (SPG1). These three disorders represent a clinical spectrum that varies not only between families but sometimes also within families. To date, 14 independent L1 mutations have been reported and shown to be disease causing. Here we report nine novel L1 mutations in X-linked hydrocephalus and MASA-syndrome families, including the first examples of mutations affecting the fibronectin type III domains of the molecule. They are discussed in relation both to phenotypes and to the insights that they provide into L1 function.

    American journal of human genetics 1995;56;6;1304-14

  • X-linked hydrocephalus and MASA syndrome present in one family are due to a single missense mutation in exon 28 of the L1CAM gene.

    Fransen E, Schrander-Stumpel C, Vits L, Coucke P, Van Camp G and Willems PJ

    Department of Medical Genetics, University of Antwerp-UIA, Belgium.

    Human molecular genetics 1994;3;12;2255-6

  • MASA syndrome is due to mutations in the neural cell adhesion gene L1CAM.

    Vits L, Van Camp G, Coucke P, Fransen E, De Boulle K, Reyniers E, Korn B, Poustka A, Wilson G, Schrander-Stumpel C et al.

    Department of Medical Genetics, University of Antwerp, Belgium.

    MASA syndrome is a recessive X-linked disorder characterized by mental retardation, adducted thumbs, shuffling gait, aphasia and, in some cases, hydrocephalus. Since it has been shown that X-linked hydrocephalus can be caused by mutations in L1CAM, a neuronal cell adhesion molecule, we performed an L1CAM mutation analysis in eight unrelated patients with MASA syndrome. Three different L1CAM mutations were identified: a deletion removing part of the open reading frame and two point mutations resulting in amino acid substitutions. L1CAM, therefore, harbours mutations leading to either MASA syndrome or HSAS, and might be frequently implicated in X-linked mental retardation with or without hydrocephalus.

    Nature genetics 1994;7;3;408-13

  • X-linked spastic paraplegia (SPG1), MASA syndrome and X-linked hydrocephalus result from mutations in the L1 gene.

    Jouet M, Rosenthal A, Armstrong G, MacFarlane J, Stevenson R, Paterson J, Metzenberg A, Ionasescu V, Temple K and Kenwrick S

    Department of Medicine, University of Cambridge, Addenbrooke's Hospital, UK.

    X-linked hydrocephalus, spastic paraplegia type I and MASA syndrome are related disorders with loci in subchromosomal region Xq28. We have previously shown that X-linked hydrocephalus is caused by mutations in the gene for neural cell adhesion molecule L1 (L1CAM), an axonal glycoprotein involved in neuronal migration and differentiation. Here we report mutations of the L1 gene in MASA syndrome and SPG1, in addition to HSAS families. Two of the HSAS mutations would abolish cell surface expression of L1 and represent the first functional null mutations in this disorder. Our results indicate that these three syndromes from part of a clinical spectrum resulting from a heterogeneous group of mutations in the L1 gene.

    Nature genetics 1994;7;3;402-7

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

Cookies Policy | Terms and Conditions. This site is hosted by Edinburgh University and the Genes to Cognition Programme.