A new complementation assay for peroxisome-deficient cell lines.
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Amino Acid Sequence↗
Biomedical subjects
D R FitzPatrick
Publications and source records attributed to D R FitzPatrick.
Zellweger syndrome and associated phenotypes.
Until recently, the peroxisome was considered a "reactor chamber" for H2O2 producing oxidases, and it is now recognised as a versatile organelle performing complex catabolic and biosynthetic roles in the cell. Zellweger syndrome (ZS), the paradigm of human peroxisomal disorders, is characterised by neonatal hypotonia, severe neuro-developmental delay, hepatomegaly, renal cysts, senorineural deafness, retinal dysfunction, and facial dysmorphism. It is now clear that ZS is at the severe end of a phenotypic spectrum of Zellweger-like syndromes which may present for diagnosis later in childhood and even in adult life. It is important that clinical geneticists are aware of these milder clinical variants as the availability of sensitive and specific biochemical assays of peroxisomal function (for example, serum VLCFA ratios, platelet DHAP-AT activity) makes their diagnosis relatively straightforward.
Animals↗
Isolation and characterization of rat and human cDNAs encoding a novel putative peroxisomal enoyl-CoA hydratase.
We have used a PCR-based subtractive hybridization method to identify upregulated cDNAs in the livers of rats treated with a peroxisome proliferator [clofibrate or di(2-ethylhexyl) phthalate]. After four rounds of subtractive hybridization 62 differentially hybridizing clones were partially sequenced and analyzed by sequence homology searching. Of 62, 49 were identical to 14 different upregulated rat sequences in the databank (mostly genes encoding microsomal or peroxisomal enzymes), 4 of 62 were fragments of three previously unknown genes, and 9 of 62 were false positives. Two of the unknown fragments hybridized to a single novel cDNA that was found to be more than 20-fold induced by both peroxisome proliferators. The 36-kDa predicted protein product of this cDNA shows a high degree of sequence homology to enoyl-CoA hydratases of several different species and has a C-terminal peroxisomal targeting sequence. An epitope-tagged protein product of a full-length cDNA was targeted to peroxisomes in a human cell line. We named this gene, which encodes an apparent peroxisomal enoyl-CoA hydratase, ECH1. We have also identified human ECH1 cDNA and mapped its structural gene to 19q13, 3' to the ryanodine receptor, by hybridization to somatic cell hybrid DNA and chromosome 19-specific cosmid arrays. Possible roles for the ECH1 protein product in peroxisomal beta-oxidation are discussed.
Amino Acid Sequence↗
Facial clefts in the west of Scotland in the period 1980-1984: epidemiology and genetic diagnoses.
Two hundred and eighty six cases of cleft lip, cleft palate, or both were identified in a study attempting complete ascertainment of babies with facial clefts born to women resident in the west of Scotland in a five year period beginning 1 January 1980. The total birth prevalence (TBP) of these defects over this period was 1.53 per 1000. The TBP for cleft lip with or without cleft palate (CL[P] was 0.74 per 1000 and for cleft palate (CP) was 0.79 per 1000; 26% of CL[P] and 39.5% of CP cases had one or more major congenital anomaly associated with their facial cleft and in over half of these cases a specific genetic or syndrome diagnosis could be made. In comparison to previous European reports this study shows a high incidence of associated abnormalities and a remarkably low ratio of CL[P]:CP cases.
Abnormalities, Multiple↗
Genetic aspects of admissions to a paediatric intensive care unit.
Of 821 consecutive admissions to a paediatric intensive care unit, 47 (5.7%) were for chromosomal or monogenic disorders. These patients had more readmissions, longer mean stays, and a higher mortality rate than the group as a whole. In two of the four cases that died of single gene disorders, failure to store DNA made genetic counseling difficult.
Child↗
Transforming growth factor betas in mammalian embryogenesis.
Type beta transforming growth factors (TGF beta s) are members of a large superfamily of related proteins, each of which plays a pivotal role in embryonic processes. The TGF beta s per se are at least five in number, though only three isoforms have been identified in mammals. Here we will review the evidence, taken from in vitro studies on bioactivity and histochemical localization of RNAs and encoded proteins in vivo, that TGF beta 1, beta 2 and beta 3 are involved in several mammalian developmental processes, including control of growth, differentiation, tissue inductions and morphogenesis.
Animals↗
Recurrences of trisomy 18 and trisomy 13 after trisomy 21.
Between 40 years and 43 years of age, a woman had three consecutive pregnancies with different prenatally diagnosed autosomal trisomies. This is compatible with the view that the predisposition to non-disjunction is not chromosome-specific.
Adult↗