Familial Aggregation of Spelling Disability

1996 ◽  
Vol 37 (7) ◽  
pp. 817-822 ◽  
Author(s):  
Gerd Schulte-Körne ◽  
Wolfgang Deimel ◽  
Katarina Müller ◽  
Cornelius Gutenbrunner ◽  
Helmut Remschmidt
1999 ◽  
Vol 8 (S3) ◽  
pp. S13-S20 ◽  
Author(s):  
Helmut Remschmidt ◽  
K. Hennighausen ◽  
G. Schulte-Körne ◽  
W. Deimel ◽  
A. Warnke

2020 ◽  
Vol 27 (31) ◽  
pp. 5119-5136 ◽  
Author(s):  
Barbara Carpita ◽  
Donatella Marazziti ◽  
Lionella Palego ◽  
Gino Giannaccini ◽  
Laura Betti ◽  
...  

Background: Autism Spectrum Disorder (ASD) is a condition strongly associated with genetic predisposition and familial aggregation. Among ASD patients, different levels of symptoms severity are detectable, while the presence of intermediate autism phenotypes in close relatives of ASD probands is also known in literature. Recently, increasing attention has been paid to environmental factors that might play a role in modulating the relationship between genomic risk and development and severity of ASD. Within this framework, an increasing body of evidence has stressed a possible role of both gut microbiota and inflammation in the pathophysiology of neurodevelopment. The aim of this paper is to review findings about the link between microbiota dysbiosis, inflammation and ASD. Methods: Articles ranging from 1990 to 2018 were identified on PUBMED and Google Scholar databases, with keyword combinations as: microbiota, immune system, inflammation, ASD, autism, broad autism phenotype, adult. Results: Recent evidence suggests that microbiota alterations, immune system and neurodevelopment may be deeply intertwined, shaping each other during early life. However, results from both animal models and human samples are still heterogeneous, while few studies focused on adult patients and ASD intermediate phenotypes. Conclusion: A better understanding of these pathways, within an integrative framework between central and peripheral systems, might not only shed more light on neural basis of ASD symptoms, clarifying brain pathophysiology, but it may also allow to develop new therapeutic strategies for these disorders, still poorly responsive to available treatments.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Na Li ◽  
Belle W. X. Lim ◽  
Ella R. Thompson ◽  
Simone McInerny ◽  
Magnus Zethoven ◽  
...  

AbstractBreast cancer (BC) has a significant heritable component but the genetic contribution remains unresolved in the majority of high-risk BC families. This study aims to investigate the monogenic causes underlying the familial aggregation of BC beyond BRCA1 and BRCA2, including the identification of new predisposing genes. A total of 11,511 non-BRCA familial BC cases and population-matched cancer-free female controls in the BEACCON study were investigated in two sequencing phases: 1303 candidate genes in up to 3892 cases and controls, followed by validation of 145 shortlisted genes in an additional 7619 subjects. The coding regions and exon–intron boundaries of all candidate genes and 14 previously proposed BC genes were sequenced using custom designed sequencing panels. Pedigree and pathology data were analysed to identify genotype-specific associations. The contribution of ATM, PALB2 and CHEK2 to BC predisposition was confirmed, but not RAD50 and NBN. An overall excess of loss-of-function (LoF) (OR 1.27, p = 9.05 × 10−9) and missense (OR 1.27, p = 3.96 × 10−73) variants was observed in the cases for the 145 candidate genes. Leading candidates harbored LoF variants with observed ORs of 2–4 and individually accounted for no more than 0.79% of the cases. New genes proposed by this study include NTHL1, WRN, PARP2, CTH and CDK9. The new candidate BC predisposition genes identified in BEACCON indicate that much of the remaining genetic causes of high-risk BC families are due to genes in which pathogenic variants are both very rare and convey only low to moderate risk.


2021 ◽  
Vol 224 (2) ◽  
pp. S642-S643
Author(s):  
Jessica M. Page ◽  
Tsegaselassie Workalemahu ◽  
Nathan R. Blue ◽  
Alison Fraser ◽  
Michael W. Varner ◽  
...  
Keyword(s):  

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3132
Author(s):  
Anna Pocurull ◽  
Cristina Herrera-Pariente ◽  
Sabela Carballal ◽  
Joan Llach ◽  
Ariadna Sánchez ◽  
...  

Gastric adenocarcinoma (GC) is a common tumor with high morbidity and mortality. Only 7% of patients with GC are diagnosed before age 50 (early onset gastric cancer (EOGC)), and their characteristics have been poorly described. We aimed to describe clinical, molecular, and genetic characteristics of EOGC. A total of 309 patients with EOGC were retrospectively studied in four Spanish centers. Personal information, family history, and tumor information were registered. Germinal genetic analysis was performed in patients who met current criteria of a hereditary syndrome at the time of diagnosis. The median age at diagnosis was 44 years. The majority (73.3%) of tumors were diffuse, and 78.3% were diagnosed in an advanced stage. Familial aggregation of GC was present in 18/117 (15.4%) cases, and 5/117 (4.3%) met criteria for familial GC. MMR-IHC was performed in 126/309 (40.7%) tumors: 4/126 (3.1%) had loss of expression in MLH1/PMS2, without an associated germline mutation. Sixteen germline genetic analyses were performed, detecting a pathogenic variant in four (25%) cases: one in BRCA2, one in TP53, and two in CDH1. Most EOGC are diffuse and diagnosed in an advanced stage. In these patients, DNA MMR system deficiency is uncommon. Although familial aggregation was observed in only 15% of cases, a germline mutation was found in 25% of patients tested with clinical criteria. This demonstrates that EOGC has a marked genetic heterogeneity, reinforcing the importance of an accurate genetic counseling and enhancing the emerging use of multigene panels.


2019 ◽  
Vol 188 (12) ◽  
pp. 2069-2077
Author(s):  
Priya Duggal ◽  
Christine Ladd-Acosta ◽  
Debashree Ray ◽  
Terri H Beaty

Abstract The field of genetic epidemiology is relatively young and brings together genetics, epidemiology, and biostatistics to identify and implement the best study designs and statistical analyses for identifying genes controlling risk for complex and heterogeneous diseases (i.e., those where genes and environmental risk factors both contribute to etiology). The field has moved quickly over the past 40 years partly because the technology of genotyping and sequencing has forced it to adapt while adhering to the fundamental principles of genetics. In the last two decades, the available tools for genetic epidemiology have expanded from a genetic focus (considering 1 gene at a time) to a genomic focus (considering the entire genome), and now they must further expand to integrate information from other “-omics” (e.g., epigenomics, transcriptomics as measured by RNA expression) at both the individual and the population levels. Additionally, we can now also evaluate gene and environment interactions across populations to better understand exposure and the heterogeneity in disease risk. The future challenges facing genetic epidemiology are considerable both in scale and techniques, but the importance of the field will not diminish because by design it ties scientific goals with public health applications.


PLoS ONE ◽  
2011 ◽  
Vol 6 (10) ◽  
pp. e27130 ◽  
Author(s):  
Michał Kiciński ◽  
Jaco Vangronsveld ◽  
Tim S. Nawrot

2010 ◽  
Vol 25 (15) ◽  
pp. 2587-2594 ◽  
Author(s):  
Michael Y. Shino ◽  
Valerie McGuire ◽  
Stephen K. Van Den Eeden ◽  
Caroline M. Tanner ◽  
Rita Popat ◽  
...  

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