G2Cdb::Human Disease report

Disease id
D00000215
Name
Hydrocephalus
Nervous system disease
yes

Genes (1)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00001881 L1CAM
L1 cell adhesion molecule
Y (11857550) Single nucleotide polymorphism (SNP) ?
G00001881 L1CAM
L1 cell adhesion molecule
Y (17294222) Deletion (D) Y

References

  • L1CAM mutation in a boy with hydrocephalus and duplex kidneys.

    Liebau MC, Gal A, Superti-Furga A, Omran H and Pohl M

    Department of Pediatrics and Adolescent Medicine, University Hospital of Freiburg, Mathildenstrasse 1, 79106, Freiburg, Germany.

    Mutations in the X-chromosomal gene (L1CAM) for cell adhesion molecule L1 are associated with a heterogeneous group of conditions that include agenesis of the corpus callosum, hydrocephalus, spastic paraplegia, adducted thumbs and mental retardation (L1-spectrum disease, CRASH or MASA syndrome). Although L1CAM is expressed during renal development and L1cam-deficient mice have congenital malformations of the kidney and the urinary tract, L1CAM mutations have not been associated with renal anomalies in men. We report on a boy with prenatally detected hydrocephalus. After his birth, bilateral duplex kidneys and ureters, with a unilateral mega-ureter serving a hydronephrotic upper pole, as well as agenesis of the corpus callosum, adducted thumbs, spasticity, and mental retardation were recognized, fulfilling the criteria of an L1-spectrum disease. Genetic testing of the patient and his mother identified a 2 bp deletion in the invariant splice consensus sequence of intron 18 of L1CAM, predicting a largely truncated or absent protein. At the age of 9 years, 7 years after heminephrectomy, the boy has normal renal function. This observation suggests that patients with L1CAM mutations may have renal abnormalities as seen in the L1cam-deficient mouse model. L1CAM might, therefore, also be considered a possible candidate gene for renal malformations.

    Pediatric nephrology (Berlin, Germany) 2007;22;7;1058-61

  • Hydrocephalus and intestinal aganglionosis: is L1CAM a modifier gene in Hirschsprung disease?

    Parisi MA, Kapur RP, Neilson I, Hofstra RM, Holloway LW, Michaelis RC and Leppig KA

    Division of Genetics and Development, Department of Pediatrics, University of Washington and Children's Hospital and Regional Medical Center, Seattle, Washington 98105, USA. mparisi@u.washington.edu

    Congenital hydrocephalus associated with aqueductal stenosis and/or agenesis of the corpus callosum has been described in newborn males with mutations in L1CAM, a gene that encodes a neural cell adhesion molecule. These males usually have severe mental retardation and may have spastic paraplegia and adducted thumbs. In contrast, Hirschsprung disease, or absence of ganglion cells in the distal gut, has rarely been described in such individuals. We report a male infant who had severe hydrocephalus identified in the prenatal period with evidence of aqueductal stenosis and adducted thumbs at birth. He developed chronic constipation, and rectal biopsy confirmed the diagnosis of Hirschsprung disease. Molecular testing of the L1CAM gene revealed a G2254A mutation, resulting in a V752M amino acid substitution. A common polymorphism in RET, but no mutation, was identified. Our patient represents the third example of coincident hydrocephalus and Hirschsprung disease in an individual with an identified L1CAM mutation. We hypothesize that L1CAM-mediated cell adhesion may be important for the ability of ganglion cell precursors to populate the gut, and that L1CAM may modify the effects of a Hirschsprung disease-associated gene to cause intestinal aganglionosis.

    Funded by: NICHD NIH HHS: P30-HD28834; NIDDK NIH HHS: R01-DK52530

    American journal of medical genetics 2002;108;1;51-6

Literature (2)

Pubmed - human_disease

  • L1CAM mutation in a boy with hydrocephalus and duplex kidneys.

    Liebau MC, Gal A, Superti-Furga A, Omran H and Pohl M

    Department of Pediatrics and Adolescent Medicine, University Hospital of Freiburg, Mathildenstrasse 1, 79106, Freiburg, Germany.

    Mutations in the X-chromosomal gene (L1CAM) for cell adhesion molecule L1 are associated with a heterogeneous group of conditions that include agenesis of the corpus callosum, hydrocephalus, spastic paraplegia, adducted thumbs and mental retardation (L1-spectrum disease, CRASH or MASA syndrome). Although L1CAM is expressed during renal development and L1cam-deficient mice have congenital malformations of the kidney and the urinary tract, L1CAM mutations have not been associated with renal anomalies in men. We report on a boy with prenatally detected hydrocephalus. After his birth, bilateral duplex kidneys and ureters, with a unilateral mega-ureter serving a hydronephrotic upper pole, as well as agenesis of the corpus callosum, adducted thumbs, spasticity, and mental retardation were recognized, fulfilling the criteria of an L1-spectrum disease. Genetic testing of the patient and his mother identified a 2 bp deletion in the invariant splice consensus sequence of intron 18 of L1CAM, predicting a largely truncated or absent protein. At the age of 9 years, 7 years after heminephrectomy, the boy has normal renal function. This observation suggests that patients with L1CAM mutations may have renal abnormalities as seen in the L1cam-deficient mouse model. L1CAM might, therefore, also be considered a possible candidate gene for renal malformations.

    Pediatric nephrology (Berlin, Germany) 2007;22;7;1058-61

Pubmed - other

  • Hydrocephalus and intestinal aganglionosis: is L1CAM a modifier gene in Hirschsprung disease?

    Parisi MA, Kapur RP, Neilson I, Hofstra RM, Holloway LW, Michaelis RC and Leppig KA

    Division of Genetics and Development, Department of Pediatrics, University of Washington and Children's Hospital and Regional Medical Center, Seattle, Washington 98105, USA. mparisi@u.washington.edu

    Congenital hydrocephalus associated with aqueductal stenosis and/or agenesis of the corpus callosum has been described in newborn males with mutations in L1CAM, a gene that encodes a neural cell adhesion molecule. These males usually have severe mental retardation and may have spastic paraplegia and adducted thumbs. In contrast, Hirschsprung disease, or absence of ganglion cells in the distal gut, has rarely been described in such individuals. We report a male infant who had severe hydrocephalus identified in the prenatal period with evidence of aqueductal stenosis and adducted thumbs at birth. He developed chronic constipation, and rectal biopsy confirmed the diagnosis of Hirschsprung disease. Molecular testing of the L1CAM gene revealed a G2254A mutation, resulting in a V752M amino acid substitution. A common polymorphism in RET, but no mutation, was identified. Our patient represents the third example of coincident hydrocephalus and Hirschsprung disease in an individual with an identified L1CAM mutation. We hypothesize that L1CAM-mediated cell adhesion may be important for the ability of ganglion cell precursors to populate the gut, and that L1CAM may modify the effects of a Hirschsprung disease-associated gene to cause intestinal aganglionosis.

    Funded by: NICHD NIH HHS: P30-HD28834; NIDDK NIH HHS: R01-DK52530

    American journal of medical genetics 2002;108;1;51-6

© 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).

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