Genetics of human hydrocephalus

Zhang, Jun; Williams, Michael A.; Rigamonti, Daniele

doi:10.1007/s00415-006-0245-5

Cited by 165 publications

(143 citation statements)

References 109 publications

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“…Furthermore, also in animal models, some 10 genes causing hydrocephalus have been detected (Zhang et al, 2006;Tapanes-Castillo et al, 2009), but to date in humans only the L1CAM gene has been identified to be associated with the L1 syndrome. Therefore, and since hardly any polymorphisms occur in the L1CAM gene, it is tempting to consider the missense mutations, detected in the group of patients suffering from L1 syndrome, as disease-causing.…”

Section: Discussionmentioning

confidence: 99%

An updated and upgradedL1CAMmutation database

Vos

Hofstra

2010

Hum. Mutat.

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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.

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Section: Discussionmentioning

confidence: 99%

An updated and upgradedL1CAMmutation database

Vos

Hofstra

2010

Hum. Mutat.

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“…During brain development, susceptibility to hydrocephalus formation seems especially high (e.g., in congenital toxoplasmosis) (Mack et al, 1999). Observations from patients and mouse models depict some general mechanisms leading to an increase of CSF pressure, mainly an impaired CSF transport due to obstructions of the ventricular system or ependymal cell malfunction, or altered production or resorption of the CSF (Zhang et al, 2006). However, the molecular mechanisms and the specific contribution of these pathological processes to human hydrocephalus remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Nuclear Factor κB Activation Impairs Ependymal Ciliogenesis and Links Neuroinflammation to Hydrocephalus Formation

et al. 2012

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“…13 Congenital hydrocephalus may be caused by either genetic or environmental factors, which include brain malformations, intracerebral hemorrhage, maternal alcohol use, infections, or X-ray radiation during pregnancy. 111 There is growing evidence that genetic factors can be involved in the pathogenesis of hydrocephalus in humans, 77,87,92 and an estimated 40% of human cases have a genetic component. 42 However, to date, mutations in only 1 human gene (L1CAM) have been definitively linked to the development of congenital hydrocephalus, and these cases account for only 5% to 15% of likely hereditary cases.…”

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confidence: 99%

Congenital Hydrocephalus in Genetically Engineered Mice

et al. 2011

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There is evidence that genetic factors play a role in the complex multifactorial pathogenesis of hydrocephalus. Identification of the genes involved in the development of this neurologic disorder in animal models may elucidate factors responsible for the excessive accumulation of cerebrospinal fluid in hydrocephalic humans. The authors report here a brief summary of findings from 12 lines of genetically engineered mice that presented with autosomal recessive congenital hydrocephalus. This study illustrates the value of knockout mice in identifying genetic factors involved in the development of congenital hydrocephalus. Findings suggest that dysfunctional motile cilia represent the underlying pathogenetic mechanism in 8 of the 12 lines (Ulk4, Nme5, Nme7, Kif27, Stk36, Dpcd, Ak7, and Ak8). The likely underlying cause in the remaining 4 lines (RIKEN 4930444A02, Celsr2, Mboat7, and transgenic FZD3) was not determined, but it is possible that some of these could also have ciliary defects. For example, the cerebellar malformations observed in RIKEN 4930444A02 knockout mice show similarities to a number of developmental disorders, such as Joubert, Meckel-Gruber, and Bardet-Biedl syndromes, which involve mutations in ciliarelated genes. Even though the direct relevance of mouse models to hydrocephalus in humans remains uncertain, the high prevalence of familial patterns of inheritance for congenital hydrocephalus in humans suggests that identification of genes responsible for development of hydrocephalus in mice may lead to the identification of homologous modifier genes and susceptibility alleles in humans. Also, characterization of mouse models can enhance understanding of important cell signaling and developmental pathways involved in the pathogenesis of hydrocephalus.

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Genetics of human hydrocephalus

Cited by 165 publications

References 109 publications

An updated and upgradedL1CAMmutation database

An updated and upgradedL1CAMmutation database

Nuclear Factor κB Activation Impairs Ependymal Ciliogenesis and Links Neuroinflammation to Hydrocephalus Formation

Congenital Hydrocephalus in Genetically Engineered Mice

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