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Inborn Errors of Peroxisome Biogenesis and Brain Malformation: Clinical and Biochemical Studies *
Author(s) -
SUZUKI Yasuyuki,
SHIMOZAWA Nobuyuki,
ORII Tadao
Publication year - 1995
Publication title -
congenital anomalies
Language(s) - English
Resource type - Journals
eISSN - 1741-4520
pISSN - 0914-3505
DOI - 10.1111/j.1741-4520.1995.tb00299.x
Subject(s) - zellweger syndrome , peroxisome , polymicrogyria , peroxisomal disorder , complementation , plasmalogen , biology , positional cloning , pathogenesis , gene , endocrinology , genetics , mutant , neuroscience , epilepsy , immunology , phospholipid , membrane
Zellweger's cerebro‐hepato‐renal syndrome is characterized by the absence of peroxisomes, severe neurologic manifestations, and neuropathological findings such as polymicrogyria and neuronal heterotopia which are based on disturbances of neuronal migration. We investigated the pathogenesis of peroxisome‐deficient disorders in attempts to clarify the molecular basis of these brain dysgenesis. Complementation analysis revealed that at least 9 genes contribute to the formation of peroxisomes. One of these gene products, peroxisome assembly factor‐1 (PAF‐1), was isolated, using a functional cloning method and a mutant Chinese hamster ovary cell line with defective peroxisomes. PAF‐1 restored the peroxisomes and biochemical abnormalities in fibroblasts from patients with Zellweger syndrome and who belonged to complementation group F. Defects in PAF‐1 would result in dysfunction of peroxisomal membrane or in the transport machinery of peroxisomal proteins, and metabolic disturbances such as accumulation of very long chain fatty acids and defects in plasmalogen may occur.