#300387
Table of Contents
Alternative titles; symbols
A number sign (#) is used with this entry because of evidence that X-linked intellectual developmental disorder-63 (XLID63) is caused by mutation in the ACSL4 (300157) gene.
Raynaud et al. (2000) reported a 4-generation family with nonspecific nonsyndromic X-linked mental retardation. Affected males showed nonprogressive mental retardation ranging from severe to moderate, without seizures, whereas carrier females showed highly variable cognitive capacities, ranging from moderate mental retardation to normal intelligence.
Raynaud et al. (2000) reported a 4-generation family with nonspecific nonsyndromic X-linked mental retardation mapped between DXS990 and DXS1227 (Xq21.33-q27.1) with a maximum lod at theta = 0.0 of 2.14 at DXS1001.
In the proband of the family reported by Raynaud et al. (2000) as MRX63, Meloni et al. (2002) identified a mutation in the ACSL4 gene (300157.0001). The proband of a second affected family carried a mutation in the 3-prime splice site of intron 10 of the ACSL4 gene (300157.0002). Mental retardation was severe. Six of 6 informative carrier females in family MRX63 showed completely skewed X inactivation in leukocytes. Similarly, 3 of 3 carrier females from 2 different families with ATS-MR (300194) showed completely skewed X inactivation in leukocytes, as did the carrier mother of the proband of the second family.
In a family with nonsyndromic X-linked mental retardation (MRX68), Longo et al. (2003) identified a mutation in the ACSL4 gene (300157.0003). Neurocognitive levels ranged from mild to moderate in affected males and were borderline in female carriers. X-inactivation studies in the female carriers showed 100% skewed inactivation in all of them.
Zhang et al. (2009) demonstrated that the Drosophila ACSL-like protein, Acsl, and ACSL4 are highly conserved, allowing ACSL4 to substitute for Acsl in organismal viability, lipid storage, and the neural wiring in the visual center. In neurodevelopment, production of decapentaplegic (Dpp), a BMP-like protein in Drosophila, diminished specifically in the larval brain of Drosophila Acsl mutants. Consistent with the Dpp reduction, the number of glial cells and neurons dramatically decreased and the retinal axons mistargeted in the visual cortex. All of these defects in Drosophila brain were rescued by the wildtype ACSL4 but not by the mutant products found in nonsyndromic X-linked mental retardation patients. Expression of an MRX63-associated ACSL4 mutant form in a wildtype background led to lesions in the visual center, suggesting a dominant-negative effect. Zhang et al. (2009) proposed a connection between ACSL4 and the BMP pathway in neurodevelopment.
Longo, I., Frints, S. G. M., Fryns, J.-P., Meloni, I., Pescucci, C., Ariani, F., Borghgraef, M., Raynaud, M., Marynen, P., Schwartz, C., Renieri, A., Froyen, G. A third MRX family (MRX68) is the result of mutation in the long chain fatty acid-CoA ligase 4 (FACL4) gene: proposal of a rapid enzymatic assay for screening mentally retarded patients. J. Med. Genet. 40: 11-17, 2003. [PubMed: 12525535, related citations] [Full Text]
Meloni, I., Muscettola, M., Raynaud, M., Longo, I., Bruttini, M., Moizard, M.-P., Gomot, M., Chelly, J., des Portes, V., Fryns, J.-P., Ropers, H.-H., Magi, B., Bellan, C., Volpi, N., Yntema, H. G., Lewis, S. E., Schaffer, J. E., Renieri, A. FACL4, encoding fatty acid-CoA ligase 4, is mutated in nonspecific X-linked mental retardation. Nature Genet. 30: 436-440, 2002. [PubMed: 11889465, related citations] [Full Text]
Raynaud, M., Moizard, M.-P., Dessay, B., Briault, S., Toutain, A., Gendrot, C., Ronce, N., Moraine, C. Systematic analysis of X-inactivation in 19 XLMR families: extremely skewed profiles in carriers in three families. Europ. J. Hum. Genet. 8: 253-258, 2000. [PubMed: 10854107, related citations] [Full Text]
Zhang, Y., Chen, D., Wang, Z. Analyses of mental dysfunction-related ACSl4 (sic) in Drosophila reveal its requirement for Dpp/BMP production and visual wiring in the brain. Hum. Molec. Genet. 18: 3894-3905, 2009. [PubMed: 19617635, related citations] [Full Text]
Alternative titles; symbols
ORPHA: 777; DO: 0112050;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| Xq23 | Intellectual developmental disorder, X-linked 63 | 300387 | X-linked dominant | 3 | ACSL4 | 300157 |
A number sign (#) is used with this entry because of evidence that X-linked intellectual developmental disorder-63 (XLID63) is caused by mutation in the ACSL4 (300157) gene.
Raynaud et al. (2000) reported a 4-generation family with nonspecific nonsyndromic X-linked mental retardation. Affected males showed nonprogressive mental retardation ranging from severe to moderate, without seizures, whereas carrier females showed highly variable cognitive capacities, ranging from moderate mental retardation to normal intelligence.
Raynaud et al. (2000) reported a 4-generation family with nonspecific nonsyndromic X-linked mental retardation mapped between DXS990 and DXS1227 (Xq21.33-q27.1) with a maximum lod at theta = 0.0 of 2.14 at DXS1001.
In the proband of the family reported by Raynaud et al. (2000) as MRX63, Meloni et al. (2002) identified a mutation in the ACSL4 gene (300157.0001). The proband of a second affected family carried a mutation in the 3-prime splice site of intron 10 of the ACSL4 gene (300157.0002). Mental retardation was severe. Six of 6 informative carrier females in family MRX63 showed completely skewed X inactivation in leukocytes. Similarly, 3 of 3 carrier females from 2 different families with ATS-MR (300194) showed completely skewed X inactivation in leukocytes, as did the carrier mother of the proband of the second family.
In a family with nonsyndromic X-linked mental retardation (MRX68), Longo et al. (2003) identified a mutation in the ACSL4 gene (300157.0003). Neurocognitive levels ranged from mild to moderate in affected males and were borderline in female carriers. X-inactivation studies in the female carriers showed 100% skewed inactivation in all of them.
Zhang et al. (2009) demonstrated that the Drosophila ACSL-like protein, Acsl, and ACSL4 are highly conserved, allowing ACSL4 to substitute for Acsl in organismal viability, lipid storage, and the neural wiring in the visual center. In neurodevelopment, production of decapentaplegic (Dpp), a BMP-like protein in Drosophila, diminished specifically in the larval brain of Drosophila Acsl mutants. Consistent with the Dpp reduction, the number of glial cells and neurons dramatically decreased and the retinal axons mistargeted in the visual cortex. All of these defects in Drosophila brain were rescued by the wildtype ACSL4 but not by the mutant products found in nonsyndromic X-linked mental retardation patients. Expression of an MRX63-associated ACSL4 mutant form in a wildtype background led to lesions in the visual center, suggesting a dominant-negative effect. Zhang et al. (2009) proposed a connection between ACSL4 and the BMP pathway in neurodevelopment.
Longo, I., Frints, S. G. M., Fryns, J.-P., Meloni, I., Pescucci, C., Ariani, F., Borghgraef, M., Raynaud, M., Marynen, P., Schwartz, C., Renieri, A., Froyen, G. A third MRX family (MRX68) is the result of mutation in the long chain fatty acid-CoA ligase 4 (FACL4) gene: proposal of a rapid enzymatic assay for screening mentally retarded patients. J. Med. Genet. 40: 11-17, 2003. [PubMed: 12525535] [Full Text: https://doi.org/10.1136/jmg.40.1.11]
Meloni, I., Muscettola, M., Raynaud, M., Longo, I., Bruttini, M., Moizard, M.-P., Gomot, M., Chelly, J., des Portes, V., Fryns, J.-P., Ropers, H.-H., Magi, B., Bellan, C., Volpi, N., Yntema, H. G., Lewis, S. E., Schaffer, J. E., Renieri, A. FACL4, encoding fatty acid-CoA ligase 4, is mutated in nonspecific X-linked mental retardation. Nature Genet. 30: 436-440, 2002. [PubMed: 11889465] [Full Text: https://doi.org/10.1038/ng857]
Raynaud, M., Moizard, M.-P., Dessay, B., Briault, S., Toutain, A., Gendrot, C., Ronce, N., Moraine, C. Systematic analysis of X-inactivation in 19 XLMR families: extremely skewed profiles in carriers in three families. Europ. J. Hum. Genet. 8: 253-258, 2000. [PubMed: 10854107] [Full Text: https://doi.org/10.1038/sj.ejhg.5200437]
Zhang, Y., Chen, D., Wang, Z. Analyses of mental dysfunction-related ACSl4 (sic) in Drosophila reveal its requirement for Dpp/BMP production and visual wiring in the brain. Hum. Molec. Genet. 18: 3894-3905, 2009. [PubMed: 19617635] [Full Text: https://doi.org/10.1093/hmg/ddp332]
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