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(1): 11-7, 2003 Jan.
Article
em En
| MEDLINE
| ID: mdl-12525535
ABSTRACT
BACKGROUND:
The gene encoding fatty acid CoA ligase 4 (FACL4) is mutated in families with non-specific X linked mental retardation (MRX) and is responsible for cognitive impairment in the contiguous gene syndrome ATS-MR (Alport syndrome and mental retardation), mapped to Xq22.3. This finding makes this gene a good candidate for other mental retardation disorders mapping in this region.METHODS:
We have screened the FACL4 gene in eight families, two MRX and six syndromic X linked mental retardation (MRXS), mapping in a large interval encompassing Xq22.3.RESULTS:
We have found a missense mutation in MRX68. The mutation (c.1001C>T in the brain isoform) cosegregates with the disease and changes a highly conserved proline into a leucine (p.P375L) in the first luciferase domain, which markedly reduces the enzymatic activity. Furthermore, all heterozygous females showed completely skewed X inactivation in blood leucocytes, as happens in all reported females with other FACL4 point mutations or deletions.CONCLUSIONS:
Since the FACL4 gene is highly expressed in brain, where it encodes a brain specific isoform, and is located in hippocampal and cerebellar neurones, a role for this gene in cognitive processes can be expected. Here we report the third MRX family with a FACL4 mutation and describe the development of a rapid enzymatic assay on peripheral blood that we propose as a sensitive, robust, and efficient diagnostic tool in mentally retarded males.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Testes Genéticos
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Coenzima A Ligases
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Mutação de Sentido Incorreto
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Proteínas de Saccharomyces cerevisiae
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Deficiência Intelectual Ligada ao Cromossomo X
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Prognostic_studies
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Screening_studies
Limite:
Adolescent
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Adult
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Child
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Female
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Humans
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Infant
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Male
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Middle aged
Idioma:
En
Revista:
J Med Genet
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Itália