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R Brian Lowry

Publications and source records attributed to R Brian Lowry.

10 recordsLinked to original sources
PubMed2006

Trends of selected malformations in relation to folic acid recommendations and fortification: an international assessment.

BACKGROUND: Two crucial issues relative to the benefits and impact of folic acid in the prevention of birth defects are whether supplementation recommendations alone, without fortification, are effective in reducing the population-wide rates of neural tube defects (NTDs), and whether such policies can reduce the occurrence of other birth defects. Using data from 15 registries, we assessed rates and trends of 14 major defects, including NTDs, in areas with official recommendations or fortification to assess the effectiveness of recommendations and fortification on a wide range of major birth defects. METHODS: We evaluated surveillance data through 2003 on major birth defects from population-based registries from Europe, North America, and Australia. All included ascertainment of pregnancy terminations (where legal). Trends before and after policies or fortification were assessed via Poisson regression and were compared via rate ratios. RESULTS: Significant changes in trends were seen for NTDs in areas with fortification but not in areas with supplementation recommendations alone. For other major birth defects, there was an overall lack of major trend changes after recommendations or fortification. However, some significant declines were observed for select birth defects in individual areas. CONCLUSIONS: Recommendations alone remain an ineffective approach in translating the known protective effect of folic acid in population-wide decline in NTD rates. Fortification appears to be effective in reducing NTDs. The effect on other birth defects remains unclear.

Dietary Supplements↗
PubMed2005

Risk and benefit of drug use during pregnancy.

Environmental teratogenic factors (e.g. alcohol) are preventable. We focus our analysis on human teratogenic drugs which are not used frequently during pregnancy. The previous human teratogenic studies had serious methodological problems, e.g. the first trimester concept is outdated because environmental teratogens cannot induce congenital abnormalities in the first month of gestation. In addition, teratogens usually cause specific congenital abnormalities or syndromes. Finally, the importance of chemical structures, administrative routes and reasons for treatment at the evaluation of medicinal products was not considered. On the other hand, in the so-called case-control epidemiological studies in general recall bias was not limited. These biases explain that the teratogenic risk of drugs is exaggerated, while the benefit of medicine use during pregnancy is underestimated. Thus, a better balance is needed between the risk and benefit of drug treatments during pregnancy. Of course, we have to do our best to reduce the risk of teratogenic drugs as much as possible, however, it is worth stressing the preventive effect of drugs for maternal diseases (e.g. diabetes mellitus and hyperthermia) related congenital abnormalities.

Journal Article↗
PubMed2005

Clinical and mutational spectrum of Mowat-Wilson syndrome.

Mowat-Wilson Syndrome is a recently delineated mental retardation syndrome usually associated with multiple malformations and a recognizable facial phenotype caused by defects of the transcriptional repressor ZFHX1B. To address the question of clinical and mutational variability, we analysed a large number of patients with suspected Mowat-Wilson Syndrome (MWS). Without prior knowledge of their mutational status, 70 patients were classified into "typical MWS", "ambiguous" and "atypical" groups according to their facial phenotype. Using FISH, qPCR and sequencing, ZFHX1B deletions, splice site or truncating mutations were detected in all 28 patients classified as typical MWS. No ZFHX1B defect was apparent in the remaining 15 cases with ambiguous facial features or in the 27 atypical patients. Genotype-phenotype analysis confirmed that ZFHX1B deletions and stop mutations result in a recognizable facial dysmorphism with associated severe mental retardation and variable malformations such as Hirschsprung disease and congenital heart defects. Our findings indicate that structural eye anomalies such as microphthalmia should be considered as part of the MWS spectrum. We also show that agenesis of the corpus callosum and urogenital anomalies (especially hypospadias) are significant positive predictors of a ZFHX1B defect. Based on our observation of affected siblings and the number of MWS cases previously reported, we suggest a recurrence risk of around 1%. The lack of missense mutations in MWS and MWS-like patients suggests there may be other, as yet unrecognized phenotypes, associated with missense mutations of this transcription factor.

Abnormalities, Multiple↗
PubMed2005

A locus for Bowen-Conradi syndrome maps to chromosome region 12p13.3.

Bowen-Conradi syndrome (BCS) is a lethal autosomal recessive disorder with an estimated incidence of 1 in 355 live births in the Hutterite population. A few cases have been reported in other populations. Here, we report the results of a genome-wide scan and fine mapping of the BCS locus in Hutterite families. By linkage and haplotype analysis the BCS locus was mapped to a 3.5 cM segment (1.9 Mbp) in chromosome region 12p13.3 bounded by F8VWF and D12S397. When genealogical relationships among the families were taken into account in the linkage analysis, the evidence for linkage was stronger and the number of potentially linked regions was reduced to one. Under the assumption that all the Hutterite patients were identical by descent for a disease-causing mutation, haplotype analysis was used to infer likely historical recombinants and thereby narrow the candidate region to a chromosomal segment shared in common by all the affected children. This study also demonstrates that BCS and cerebro-oculo-facial-skeletal syndrome (COFS) are genetically distinct.

Abnormalities, Multiple↗
PubMed2005

SALL1 mutation analysis in Townes-Brocks syndrome: twelve novel mutations and expansion of the phenotype.

Townes-Brocks syndrome is an autosomal dominantly inherited disorder, which comprises multiple birth defects including renal, ear, anal, and limb malformations. TBS has been shown to result from mutations in SALL1, a human gene related to the developmental regulator SAL of Drosophila melanogaster. The SALL1 gene product is a zinc finger protein thought to act as a transcription factor. It contains four highly conserved, evenly distributed C2H2 double zinc finger domains. A single C2H2 motif is attached to the second domain, and at the amino terminus SALL1 contains a C2HC motif. Most mutations causing TBS are clustered in the N-terminal third of the SALL1 coding region and result in the production of truncated proteins containing only one or none of the C2H2 domains and the N-terminal transcriptional repressor domain of SALL1. Twenty-three SALL1 mutations were reported prior to this work, 22 of which are located in exon 2, 5' of the second double zinc finger-encoding region. Here we present 12 novel mutations in SALL1 associated with Townes-Brocks syndrome in 13 unrelated families. These include three nonsense mutations, three short insertions and six short deletions. Thus the number of SALL1 mutations increases to 35. Rare phenotypical features among mutation positive patients include hypothyroidism, vaginal aplasia with bifid uterus, cryptorchidism, bifid scrotum without hypospadia scrotalis, unilateral chorioretinal coloboma with loss of vision, dorsal hypoplasia of the corpus callosum, and umbilical hernia.

Abnormalities, Multiple↗
PubMed2005

Anophthalmia and microphthalmia in the Alberta Congenital Anomalies Surveillance System.

BACKGROUND: A higher than expected rate of anophthalmia/microphthalmia (A/M) for 1999 was noted in both the Alberta Congenital Anomalies Surveillance System (ACASS) and the Canadian Congenital Anomalies Surveillance System (CCASS). Since this increase was at variance with the previous 19 years, we performed a review to determine whether the increase was true and, if so, the possible explanation. METHODS: We reviewed the records of the cases of A/M in the ACASS together with the accompanying attachments (e.g., consultant, autopsy and chromosome reports) for 1991-2001. In addition, we contacted all 91 registered ophthalmologists in Alberta. Letters were also written to the Edmonton and Calgary offices of the Canadian National Institute for the Blind (CNIB). RESULTS: Sixty cases of A/M were ascertained over the study period. Of the 88 active ophthalmologists in the province, 21 (24%) replied, but no new cases were ascertained from this source. No replies were received from the CNIB. We constructed five categories of clinical phenotypes for the 60 cases: 20 had a chromosomal etiology, 13 had a recognized syndrome or association, 16 had extraocular malformations, 5 had other eye anomalies, and 6 had A/M only. Pregnancy terminations were not included. The higher rate in 1999 was mainly due to cases with a chromosomal etiology or a recognized syndrome or association. There was no indication that a teratogen was causing a cluster of A/M cases, as our annual rates were comparable to those for other jurisdictions not only in Canada but also in other countries. INTERPRETATION: Our review confirmed that the rate of A/M in Alberta in 1999 was high but that the increase was mainly due to five cases of trisomy 13 together with one case associated with a syndrome (Meckel-Gruber). Our findings provide reassurance that there was no environmental cause of clustering of anophthalmia or microphthalmia. This review demonstrates the importance of ongoing population-based surveillance in providing baseline birth prevalence rates for evaluating trends and clusters.

Alberta↗
PubMed2002

Bowen-Conradi syndrome in non Hutterite infant.

The authors' review their experience of Bowen-Conradi syndrome and the available literature. They point out that there have been three previously published reports of possible Bowen-Conradi syndrome in non Hutterite children.

Abnormalities, Multiple↗