RESUMEN
Mutations in the lipoprotein lipase (LPL) gene are the most important cause of familial chylomicronemia with over 70 mutations being recorded to date. Thus far de novo mutations have not been described. Here we report on the molecular analysis of the family of a patient previously reported to be LPL deficient on the basis of compound heterozygosity for the Arg243His and Ile225Thr mutations, the latter being the first and only mutation identified in the loop region of LPL. Both parents of the propositus were screened for the presence of these two mutations to confirm their status as obligate heterozygotes and to determine the mutation allocation. Although paternal inheritance of the Arg243His allele could be established, maternal DNA did not show carrier status for the Ile225Thr substitution. An examination of maternity, using LPL restriction fragment length polymorphisms four polymorphic CA repeats and ApoE genotypes, was consistent with correct biological parentage for the propositus. Therefore, we conclude that the Ile225Thr mutation constitutes a de novo event, the first to be reported in the LPL gene.
Asunto(s)
Hiperlipoproteinemia Tipo I/genética , Isoleucina/genética , Lipoproteína Lipasa/genética , Mutación , Treonina/genética , Adulto , Anciano , Sustitución de Aminoácidos , Apolipoproteínas E/sangre , Apolipoproteínas E/genética , Repeticiones de Dinucleótido/genética , Exones/genética , Genotipo , Haplotipos , Humanos , Hiperlipoproteinemia Tipo I/sangre , Lípidos/sangre , Masculino , Linaje , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
A large family with autosomal dominant aniridia is described. One of the family members presented with reduced visual acuity, nystagmus, slightly distorted macular reflex, but normal irides and clear media. Because of the high variability in expression of aniridia, even within family, a diagnosis of aniridia could not be excluded. However linkage analysis using tightly linked chromosome 11p13 markers flanking the aniridia locus (catalase, D11S151, and D11S325) made it highly unlikely that this patient inherited the aniridia gene from his affected mother.
Asunto(s)
Aniridia/genética , ADN/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aniridia/diagnóstico , Cromosomas Humanos Par 11 , Familia , Femenino , Expresión Génica , Ligamiento Genético/genética , Variación Genética/genética , Glaucoma/genética , Humanos , Masculino , Persona de Mediana Edad , Nistagmo Patológico/genética , Linaje , Agudeza VisualRESUMEN
Mitogen-activated protein kinase phosphatases (MKPs) play a central role in a variety of signaling pathways. We recently described a novel murine MKP, M3/6, which is uniquely specific for c-Jun N-terminal kinase/stress-activated protein kinase and p38 kinase. Here we report the localization of the human orthologue of this gene, HB5, to within 150 kb of H19 on human chromosome 11p15.5. The gene consists of six exons. Two of the introns in HB5 are not found in other genes of this family, suggesting an evolutionary split between MKPs displaying specificity toward different MAP kinases. An intronless pseudogene is present on chromosome 10q11.2. Although 11p15.5 is an imprinted region, HB5 is almost entirely unmethylated on both alleles in lymphocytes. Chromosome 11p15 has been implicated in the development of a number of tumor types, including lung, a tissue known to express this gene. Loss of heterozygosity was found in one of eight informative lung tumors studied.