Comprehensive population screening in the Ashkenazi Jewish population for recurrent disease‐causing variants

Shi, Lisong; Webb, Bryn D.; Birch, Ashley H.; Elkhoury, Lama; McCarthy, J.; Cai, Xiaoqiang; Oishi, Kimihiko; Mehta, Lakshmi; Diaz, George A.; Edelmann, Lisa; Kornreich, Ruth

doi:10.1111/cge.12834

Cited by 27 publications

(19 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All of these conditions have founder mutations in the Ashkenazi Jewish population and the carrier frequency in the Ashkenazi Jewish population of these conditions ranges from 1 in 18 to 1 in 168 (Gross et al, ; Rink et al, ). Many laboratories now offer expanded carrier screening panels, which include conditions that have much lower carrier frequencies in the Ashkenazi Jewish population (Mastantuoni et al, ; Shi et al, ). Uptake of carrier screening in the Ashkenazi Jewish population was positive and affected individuals for some of these conditions are rarely seen in the Ashkenazi Jewish community today (Klugman & Gross, ).…”

Section: Discussionmentioning

confidence: 99%

Study of carrier frequency of Warsaw breakage syndrome in the Ashkenazi Jewish population and presentation of two cases

Rabin¹,

Hirsch²,

Johansson³

et al. 2019

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Warsaw breakage syndrome (WABS), caused by bi-allelic variants in the DDX11 gene, is a rare cohesinopathy characterized by pre-and postnatal growth retardation, microcephaly, intellectual disability, facial dysmorphia, and sensorineural hearing loss due to cochlear hypoplasia. The DDX11 gene codes for an iron-sulfur DNA helicase in the Superfamily 2 helicases and plays an important role in genomic stability and maintenance. Fourteen individuals with WABS have been previously reported in the medical literature. Affected individuals have been of various ethnic backgrounds with different pathogenic variants. We report two unrelated individuals of Ashkenazi Jewish descent affected with WABS, who are homozygous for the c.1763-1G>C variant in the DDX11 gene. Their phenotype is consistent with previously reported individuals. RNA studies showed that this variant causes an alternative splice acceptor site leading to a frameshift in the open reading frame. Carrier screening of the c.1763-1G>C variant in the Jewish population revealed a high carrier frequency of 1 in 68 in the Ashkenazi Jewish population. Due to the high carrier frequency and the low number of affected individuals, we hypothesize a high rate of miscarriage of homozygous fetuses and/or subfertility for carrier couples. If the carrier frequency is reproducible in additional Ashkenazi Jewish populations, we suggest including DDX11 to Ashkenazi Jewish carrier screening panels.

show abstract

Section: Discussionmentioning

confidence: 99%

Study of carrier frequency of Warsaw breakage syndrome in the Ashkenazi Jewish population and presentation of two cases

Rabin¹,

Hirsch²,

Johansson³

et al. 2019

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…Also, different genome wide association studies (GWAS) have identified genetic variants as determinants of microbiome composition, regardless of PD status [40][41][42]. Genetic drift and founder effects can lead to different genetic backgrounds in different populations [43]. Various microbiome studies in PD have attempted to limit the influence of the genetic background through the exclusion of subjects with a positive family history and/or age of onset below 50 years.…”

Section: Study Population and Assessmentsmentioning

confidence: 99%

Increasing Comparability and Utility of Gut Microbiome Studies in Parkinson’s Disease: A Systematic Review

Boertien

Pereira

Aho

et al. 2019

JPD

136

160

View full text Add to dashboard Cite

Gut microbiota have been studied in relation to the pathophysiology of Parkinson's disease (PD) due to the early gastrointestinal symptomatology and presence of alpha-synuclein pathology in the enteric nervous system, hypothesized to ascend via the vagal nerve to the central nervous system. Accordingly, sixteen human case-control studies have published gut microbiome composition changes in PD and reported over 100 differentially abundant taxa covering all taxonomic levels from phylum to genus or species, depending on methodology. While certain findings were replicated across several studies, various contradictory findings were reported. Here, differences in methodologies and the presence of possible confounders in the study populations are assessed for their potential to confound the results of gut microbiome studies in PD. Gut microbiome studies in PD exhibited considerable variability with respect to the study population, sample transport conditions, laboratory protocols and sequencing, bioinformatics pipelines, and biostatistical methods. To move from the current heterogeneous dataset towards clinically relevant biomarkers and the identification of putative therapeutic targets, recommendations are derived from the limitations of the available studies to increase the future comparability of microbiome studies in PD. In addition, integration of currently available data on the gut microbiome in PD is proposed to identify robust gut microbiome profiles in PD. Furthermore, expansion of the current dataset with atypical parkinsonism cohorts, prodromal and treatmentnaïve de novo PD subjects, measurements of fecal microbial concentrations and multi-omics assessments are required to provide clinically relevant biomarkers and reveal therapeutic targets within the gut microbiome of PD.

show abstract

“…Indicated groups include Ashkenazi Jews and Israeli Arabs. 2,3 Severe factor XI deficiency, also known as hemophilia C, is reported to have prevalence of 1:450 within the Ashkenazi Jewish community as compared with a 1:10 6 worldwide. 4 More modest factor XI deficiency, some of which may be autosomal dominant, has been estimated to be more common at 1 in 10 000 to 50 000.…”

Section: Introductionmentioning

confidence: 99%

Factor XI deficiency is associated with lower risk for cardiovascular and venous thromboembolism events

Preis

Hirsch

Kotler

et al. 2017

Blood

180

131

View full text Add to dashboard Cite

Key Points• Factor XI deficiency is associated with reduced risk of cardiovascular events.• Factor XI deficiency is associated with reduced risk of VTE.Factor XI deficiency is one of the rare inherited coagulation factor deficiencies. However, its incidence is high within the Ashkenazi Jewish community. Because factor XI displays both procoagulant and antifibrinolytic activities, it has been postulated that an underlying cardiovascular benefit may exist with factor XI deficiency. This historical cohort study was performed using the electronic database of Clalit Health Services, the largest health care provider in Israel. All adults tested for factor XI activity between 2002 and 2014 were included in the study. Factor XI activity was classified into 3 categories: normal (activity >50%), mild deficiency (activity 5 30%-50%), and moderate-severe deficiency (activity £30%). The cohort was followed until 31 December 2015 for incidence of cardiovascular events (composite of myocardial infarction, stroke, and transient ischemic attack) and venous thromboembolism (VTE). Of the 10 193 included patients, 8958 (88.9%) had normal factor XI activity, 690 (6.8%) had mild deficiency, and 542 (5.3%) had moderate-severe deficiency. Compared with individuals with normal activity, the adjusted hazard ratio (HR) for cardiovascular events was 0.52 (95% confidence interval [CI], 0.31-0.87) in those with mild deficiency, and 0.57 (95% CI, 0.35-0.93) in those with moderate-severe factor XI deficiency. The incidence of VTE was lower in those with factor XI deficiency (activity <50%) compared with those with normal activity; adjusted HR 5 0.26 (95% CI, 0.08-0.84). In summary, factor XI deficiency is associated with decreased incidence of cardiovascular events and VTE. (Blood. 2017;129(9):1210-1215

show abstract

Comprehensive population screening in the Ashkenazi Jewish population for recurrent disease‐causing variants

Cited by 27 publications

References 14 publications

Study of carrier frequency of Warsaw breakage syndrome in the Ashkenazi Jewish population and presentation of two cases

Study of carrier frequency of Warsaw breakage syndrome in the Ashkenazi Jewish population and presentation of two cases

Increasing Comparability and Utility of Gut Microbiome Studies in Parkinson’s Disease: A Systematic Review

Factor XI deficiency is associated with lower risk for cardiovascular and venous thromboembolism events

Contact Info

Product

Resources

About