Genetics in medicine : official journal of the American College of Medical Genetics · 2006
Quantifying the carrier female phenotype in Pelizaeus-Merzbacher disease.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Hurst Stephanie, Garbern James, Trepanier Angela, Gow Alexander
Аннотация
PURPOSE: Pelizaeus-Merzbacher disease and spastic paraplegia type 2 are allelic X-linked disorders that principally affect males and are caused by mutations in the proteolipid protein 1 gene. Neurologic symptoms are occasionally observed in carrier females, and anecdotal evidence suggests that these clinical signs are more likely in families with affected males. We analyze 40 pedigrees to determine whether such a link exists.
METHODS: From a chart review of patients from Wayne State University, we categorize patients according to disease severity and type of genetic lesion within the proteolipid protein 1 gene. We then analyze the clinical data using nonparametric t tests and analyses of variance.
RESULTS: Our analyses formally demonstrate the link between mild disease in males and symptoms in carrier female relatives. Conversely, mutations causing severe disease in males rarely cause clinical signs in carrier females. The greatest risk of disease in females is found for nonsense/indel or null mutations. Missense mutations carry moderate risk. The lowest risk, which represents the bulk of families with Pelizaeus-Merzbacher disease, is associated with proteolipid protein 1 gene duplications.
CONCLUSIONS: Effective genetic counseling of Pelizaeus-Merzbacher disease and spastic paraplegia carrier females must include an assessment of disease severity in affected male relatives.
METHODS: From a chart review of patients from Wayne State University, we categorize patients according to disease severity and type of genetic lesion within the proteolipid protein 1 gene. We then analyze the clinical data using nonparametric t tests and analyses of variance.
RESULTS: Our analyses formally demonstrate the link between mild disease in males and symptoms in carrier female relatives. Conversely, mutations causing severe disease in males rarely cause clinical signs in carrier females. The greatest risk of disease in females is found for nonsense/indel or null mutations. Missense mutations carry moderate risk. The lowest risk, which represents the bulk of families with Pelizaeus-Merzbacher disease, is associated with proteolipid protein 1 gene duplications.
CONCLUSIONS: Effective genetic counseling of Pelizaeus-Merzbacher disease and spastic paraplegia carrier females must include an assessment of disease severity in affected male relatives.