RESUMO
BACKGROUND: A number of studies reports reduced hippocampal volume in individuals who engage in problematic alcohol use. However, the magnitude of the difference in hippocampal volume between individuals with v. without problematic alcohol use has varied widely, and there have been null findings. Moreover, the studies comprise diverse alcohol use constructs and samples, including clinically significant alcohol use disorders and subclinical but problematic alcohol use (e.g. binge drinking), adults and adolescents, and males and females. METHODS: We conducted the first quantitative synthesis of the published empirical research on associations between problematic alcohol use and hippocampal volume. In total, 23 studies were identified and selected for inclusion in the meta-analysis; effects sizes were aggregated using a random-effects model. RESULTS: Problematic alcohol use was associated with significantly smaller hippocampal volume (d = -0.53). Moderator analyses indicated that effects were stronger for clinically significant v. subclinical alcohol use and among adults relative to adolescents; effects did not differ among males and females. CONCLUSIONS: Problematic alcohol use is associated with reduced hippocampal volume. The moderate overall effect size suggests the need for larger samples than are typically included in studies of alcohol use and hippocampal volume. Because the existing literature is almost entirely cross-sectional, future research using causally informative study designs is needed to determine whether this association reflects premorbid risk for the development of problematic alcohol use and/or whether alcohol has a neurotoxic effect on the hippocampus.
Assuntos
Alcoolismo/patologia , Hipocampo/patologia , Adolescente , Adulto , Idoso , Alcoolismo/diagnóstico por imagem , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Juvenile polyposis (JP; OMIM 174900) is an autosomal dominant gastrointestinal hamartomatous polyposis syndrome in which patients are at risk for developing gastrointestinal cancers. Previous studies have demonstrated a locus for JP mapping to 18q21.1 (ref. 3) and germline mutations in the homolog of the gene for mothers against decapentaplegic, Drosophila, (MADH4, also known as SMAD4) in several JP families. However, mutations in MADH4 are only present in a subset of JP cases, and although mutations in the gene for phosphatase and tensin homolog (PTEN) have been described in a few families, undefined genetic heterogeneity remains. Using a genome-wide screen in four JP kindreds without germline mutations in MADH4 or PTEN, we identified linkage with markers from chromosome 10q22-23 (maximum lod score of 4.74, straight theta=0.00). We found no recombinants using markers developed from the vicinity of the gene for bone morphogenetic protein receptor 1A (BMPR1A), a serine-threonine kinase type I receptor involved in bone morphogenetic protein (BMP) signaling. Genomic sequencing of BMPR1A in each of these JP kindreds disclosed germline nonsense mutations in all affected kindred members but not in normal control individuals. These findings indicate involvement of an additional gene in the transforming growth factor-beta (TGF-beta) superfamily in the genesis of JP, and document an unanticipated function for BMP in colonic epithelial growth control.
Assuntos
Polipose Adenomatosa do Colo/genética , Mutação em Linhagem Germinativa , Proteínas Serina-Treonina Quinases/genética , Receptores de Fatores de Crescimento/genética , Proteínas Supressoras de Tumor , Polipose Adenomatosa do Colo/patologia , Adolescente , Adulto , Receptores de Proteínas Morfogenéticas Ósseas Tipo I , Criança , Pré-Escolar , Cromossomos Humanos Par 10 , Proteínas de Ligação a DNA/genética , Éxons , Feminino , Síndrome do Hamartoma Múltiplo/genética , Síndrome do Hamartoma Múltiplo/patologia , Humanos , Escore Lod , Perda de Heterozigosidade , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Dados de Sequência Molecular , PTEN Fosfo-Hidrolase , Monoéster Fosfórico Hidrolases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Fatores de Crescimento/metabolismo , Proteína Smad4 , Transativadores/genéticaRESUMO
A fetus with a 46,XX,r(17) karyotype identified initially by amniocentesis and confirmed by banding studies is described. No significant phenotypic abnormalities were identified despite isolation of the ring chromosome from multiple fetal tissues. This paucity of abnormal features of gross development is consistent with findings in 3 previously reported patients with ring 17 chromosomes.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos 16-18 , Adulto , Amniocentese , Feminino , Humanos , Fenótipo , GravidezRESUMO
BACKGROUND: Juvenile polyposis (JP) is an inherited condition predisposing to upper gastrointestinal (UGI) polyps and colorectal cancer. Two genes are known to predispose to JP, SMAD4 and bone morphogenetic protein receptor type 1A (BMPR1A). The object of this study was to determine the differences in phenotype of patients with SMAD4 or BMPR1A mutations (MUT+) compared with those without (MUT-). METHODS: DNA was extracted from 54 JP probands and used for polymerase chain reaction of all exons of SMAD4 and BMPR1A. Products were then sequenced and analyzed for mutations. Medical record data were used to create a JP database, and statistical analysis was performed using Fisher's exact and unpaired t-tests. RESULTS: Nine of 54 patients had germline SMAD4 mutations, 13 had BMPR1A mutations, and 32 had neither. There were no significant differences between SMAD4+ and BMPR1A+ cases in terms of clinical factors examined, except for a family history of UGI involvement (P <.01). There was a higher prevalence of familial cases in MUT+ patients (P =.09), >10 lower gastrointestinal polyps (P =.06), and frequency of family history of gastrointestinal cancer compared with MUT- patients (P =.01). CONCLUSIONS: Patients with germline SMAD4 or BMPR1A mutations have a more prominent JP phenotype than those without, and SMAD4 mutations predispose to UGI polyposis.