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  1. Article ; Online: Marriage patterns and reproductive decision-making in the inhabitants of a single Muslim village during a 50-year period.

    Zlotogora, Joël / Shalev, Stavit A

    Human heredity

    2014  Volume 77, Issue 1-4, Page(s) 10–15

    Abstract: Objectives: In a single Muslim village in Israel, established about 300 years ago by a small number of founders, a longitudinal study was conducted on the types of marriages and their effects on family planning, with the age at which a woman had her ... ...

    Abstract Objectives: In a single Muslim village in Israel, established about 300 years ago by a small number of founders, a longitudinal study was conducted on the types of marriages and their effects on family planning, with the age at which a woman had her first child and the size of the family assessed.
    Methods: The information for the analysis was extracted from a detailed database including individuals residing in and originating from the village.
    Results: A shift from the practice of marrying a close relative, in particular patrilateral parallel first-cousin marriages, to marrying a more remotely related individual was observed during the study period. Another major change was a significant reduction in the mean number of children born per woman from 8.7 among women born between 1930 and 1939 to 4.7 among those born between 1960 and 1969. In families in which the parents were biological relatives, the number of children was always higher than in families in which the parents were unrelated. The mean age of the mother at the birth of her first child progressively increased during the study period from 20.9 to 23.7 years. The maternal age was always higher when the spouses were from different villages than when they were biological relatives, either being first cousins or more distantly related.
    Conclusions: Significant sociodemographic changes were observed during the course of the last 50 years. However, the consequences of the long-lasting isolation of the population remain and still exert an important effect on present-day medical problems in the village.
    MeSH term(s) Consanguinity ; Demography ; Female ; History, 20th Century ; Humans ; Islam ; Israel ; Longitudinal Studies ; Marriage/ethnology ; Marriage/history ; Marriage/trends ; Maternal Age ; Parity
    Language English
    Publishing date 2014
    Publishing country Switzerland
    Document type Historical Article ; Journal Article
    ZDB-ID 2424-7
    ISSN 1423-0062 ; 0001-5652
    ISSN (online) 1423-0062
    ISSN 0001-5652
    DOI 10.1159/000357945
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  2. Article: A long-term follow up of premarital counseling in the Israeli Arab population.

    Zlotogora, Joël / Shalev, Stavit A

    Journal of community genetics

    2014  Volume 5, Issue 4, Page(s) 377–381

    Abstract: A follow up study of 168 Arab counselees that received premarital genetic counseling between 2001 and 2009, mostly since they planned to marry with a relative, was performed in 2013. Among the 156 cases in which the counselee married, 30 changed their ... ...

    Abstract A follow up study of 168 Arab counselees that received premarital genetic counseling between 2001 and 2009, mostly since they planned to marry with a relative, was performed in 2013. Among the 156 cases in which the counselee married, 30 changed their marital plans (19.2 %). Those who changed their marital plans were more often Muslim Arabs that came for counseling since they were related in particular first cousins. Among the 126 counselee that married as planned, 66 were interviewed. From these interviews, it appears that many of the counselees that were related as first cousins or closer came to premarital genetic counseling in order to decide whether to marry. Most of the couples interviewed followed the recommendations concerning the use of folic acid and genetic tests. Among the 53 consanguineous couples interviewed, 49 women had 118 children. Among these 118 children, 8 (6.8 %) were born with a severe disease in 8 different families. This rate of malformations/genetic diseases is similar to the one observed for consanguineous couples from the general Arab population in the region, suggesting therefore that the premarital counseling and the adherence to the recommendations did not change the final risk to the counselees.
    Language English
    Publishing date 2014-06-29
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2543127-4
    ISSN 1868-6001 ; 1868-310X
    ISSN (online) 1868-6001
    ISSN 1868-310X
    DOI 10.1007/s12687-014-0192-2
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  3. Article: Educational tools support informed decision-making for genetic carrier screening in a heterogenic Israeli population.

    Gafni-Amsalem, Chen / Aboleil-Zoubi, Olfat / Chervinsky, Elena / Aleme, Ola / Khayat, Morad / Bashir, Husam / Perets, Lilach Peled / Mamluk, Efrat / Hakrosh, Shadia / Kurtzman, Shoshi / Tamir, Liron / Baram-Tsabari, Ayelet / Shalev, Stavit A

    Journal of community genetics

    2023  Volume 15, Issue 2, Page(s) 137–146

    Abstract: Reproductive genetic carrier screening (RGCS) aims to provide couples with information to make informed decisions. Since 2013, the Israeli Carrier Screening Program has been offered routinely and free of charge to all Israelis of reproductive age, ... ...

    Abstract Reproductive genetic carrier screening (RGCS) aims to provide couples with information to make informed decisions. Since 2013, the Israeli Carrier Screening Program has been offered routinely and free of charge to all Israelis of reproductive age, personalized based on religion, ethnicity, and village/tribe where a disorder is frequent. This study evaluated the impact of two educational tools on an informed choice on RGCS uptake and satisfaction with counselling within a heterogeneous population in northern Israel. Participants from diverse sociodemographic population groups were randomly assigned to watch an animated film, read a booklet conveying the same information, or receive no information before counselling for RGCS, and asked to complete pre- and post-counselling questionnaires. A higher informed-decision rate was demonstrated in the film (n=93/141, 66%) and booklet (n=88/131, 67%) groups vs. the non-intervention group (n=62/143, 43%) (P<0.001), assessed by the Multidimensional Measure of Informed Choice. Multivariate logistic regression analysis revealed that allocation to an intervention group, Jewish ethnicity and higher education level, best predicted informed choice. Most participants expressed high levels of satisfaction with the counselling process, regardless of group assignment. While only a minority of participants reported seeking information prior to visiting the clinic, the pre-counselling information interventions were well accepted. Pre-counselling self-learning educational tools should be promoted, easily available, and adjusted linguistically and culturally to targeted populations, to avoid unwanted "automatic" compliance of tested individuals and maximize the potential of informed decision-making. Our study can be applied to other countries where majority and minority ethnic groups access genetic services.
    Language English
    Publishing date 2023-12-20
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2543127-4
    ISSN 1868-6001 ; 1868-310X
    ISSN (online) 1868-6001
    ISSN 1868-310X
    DOI 10.1007/s12687-023-00694-4
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  4. Article ; Online: The effect of a prior e-learning tool on genetic counseling outcomes in diverse ethnic couples with abnormal Down syndrome screening tests: A randomized controlled trial.

    Aboleil-Zoubi, Olfat / Gafni-Amsalem, Chen / Peled-Perets, Lilach / Mamluk, Efrat / Tamir, Liron / Hakrosh, Shadia / Kurtzman, Shoshana / Chervinsky, Elena / Aalimi, Ula / Husam, Bashir / Khayat, Morad / Baram-Tsabari, Ayelet / Shalev, Stavit A

    Journal of genetic counseling

    2023  

    Abstract: Genetic counseling (GC) following abnormal Down syndrome (DS) screening tests aims to ensure learning of complex medical concepts and discussion of counselees' personal desires. Pre-GC use of electronic learning tools (e-learning tools) can facilitate GC ...

    Abstract Genetic counseling (GC) following abnormal Down syndrome (DS) screening tests aims to ensure learning of complex medical concepts and discussion of counselees' personal desires. Pre-GC use of electronic learning tools (e-learning tools) can facilitate GC sessions by allowing more time for dialogue rather than learning medical and genetic concepts, enabling greater focus on the counselee's decisional, psychological, and personal needs. Few studies have investigated such tools for DS screening tests and those who have focused on screening uptake rather than abnormal results and implications. This study evaluated prenatal GC outcomes following implementation of an e-learning tool utilizing an educational animated movie for couples of varied ethnic backgrounds in northern Israel, with abnormal DS screening tests. E-learning tool impact was assessed as knowledge level, informed choices, satisfaction with the intervention and GC process, the state of anxiety and duration of the GC meeting. The 321 study participants were randomized to three groups: animation movie, booklet, and control. All participants had been asked to complete pre- and post-counseling questionnaires. Outcome scores were compared between the research groups. Results showed increased knowledge level in general among participants in the animation group; among minority participants, the highest knowledge level was in the animation group. Anxiety levels and informed choices were not statistically different among the groups. However, watching the animation, Jewish ethnicity, good level of genetic literacy, and academic degree were significant predictors of informed choice, and those who watched the animation were three times more likely to make an informed choice than the control group. Our findings suggest that this e-learning tool is efficient and acceptable for the general population. Special attention is needed for minorities with lower genetic literacy and education.
    Language English
    Publishing date 2023-08-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1117799-8
    ISSN 1573-3599 ; 1059-7700
    ISSN (online) 1573-3599
    ISSN 1059-7700
    DOI 10.1002/jgc4.1774
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  5. Article: A syndrome characterized by intra-uterine lower limb dislocation, gracile bones, clubfeet, and other skeletal features.

    Shalev, Stavit A

    American journal of medical genetics. Part A

    2007  Volume 143, Issue 4, Page(s) 395–398

    MeSH term(s) Abnormalities, Multiple/diagnosis ; Abnormalities, Multiple/embryology ; Abnormalities, Multiple/pathology ; Bone and Bones/abnormalities ; Bone and Bones/diagnostic imaging ; Bone and Bones/embryology ; Clubfoot/pathology ; Female ; Fetal Development ; Fetus/abnormalities ; Fetus/embryology ; Humans ; Knee Dislocation/diagnostic imaging ; Knee Dislocation/embryology ; Knee Dislocation/pathology ; Lower Extremity/embryology ; Lower Extremity/pathology ; Musculoskeletal System/embryology ; Radiography ; Syndrome ; Uterus/embryology
    Language English
    Publishing date 2007-01-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2108614-X
    ISSN 1552-4825
    ISSN 1552-4825
    DOI 10.1002/ajmg.a.31580
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  6. Article ; Online: MCM9 is associated with germline predisposition to early-onset cancer-clinical evidence.

    Goldberg, Yael / Aleme, Ola / Peled-Perets, Lilach / Castellvi-Bel, Sergi / Nielsen, Maartje / Shalev, Stavit A

    NPJ genomic medicine

    2021  Volume 6, Issue 1, Page(s) 78

    Abstract: Mutated MCM9 has been associated with primary ovarian insufficiency. Although MCM9 plays a role in genome maintenance and has been reported as a candidate gene in a few patients with inherited colorectal cancer (CRC), it has not been clearly established ... ...

    Abstract Mutated MCM9 has been associated with primary ovarian insufficiency. Although MCM9 plays a role in genome maintenance and has been reported as a candidate gene in a few patients with inherited colorectal cancer (CRC), it has not been clearly established as a cancer predisposition gene. We re-evaluated family members with MCM9-associated fertility problems. The heterozygote parents had a few colonic polys. Three siblings had early-onset cancer: one had metastatic cervical cancer and two had early-onset CRC. Moreover, a review of the literature on MCM9 carriers revealed that of nine bi-allelic carriers reported, eight had early-onset cancer. We provide clinical evidence for MCM9 as a cancer germline predisposition gene associated with early-onset cancer and polyposis, mainly in a recessive inheritance pattern. These observations, coupled with the phenotype in knockout mice, suggest that diagnostic testing for polyposis, CRC, and infertility should include MCM9 analysis. Early screening protocols may be beneficial for carriers.
    Language English
    Publishing date 2021-09-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2813848-X
    ISSN 2056-7944 ; 2056-7944
    ISSN (online) 2056-7944
    ISSN 2056-7944
    DOI 10.1038/s41525-021-00242-4
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  7. Article ; Online: Homozygous mutation in the APOA1BP is associated with a lethal infantile leukoencephalopathy.

    Spiegel, Ronen / Shaag, Avraham / Shalev, Stavit / Elpeleg, Orly

    Neurogenetics

    2016  Volume 17, Issue 3, Page(s) 187–190

    Abstract: Febrile-induced neurodegenerative diseases are a heterogeneous group of genetic disorders most commonly inborn errors of metabolism that result in irreversible damage involving the central nervous system. Here, we report on five siblings of ... ...

    Abstract Febrile-induced neurodegenerative diseases are a heterogeneous group of genetic disorders most commonly inborn errors of metabolism that result in irreversible damage involving the central nervous system. Here, we report on five siblings of consanguineous family who developed normally for the first 6-12 months of life then presented with a severe leukoencephalopathy following a trivial febrile illness. Using homozygosity mapping followed by whole exome sequencing, we identified a homozygous c. 281C>A mutation in the APOA1BP gene resulting in substitution of a highly conserved alanine residue with aspartic acid (p.Ala94Asp). APOA1BP encodes for epimerase that catalyzes the R to S epimerization of NAD(P)XH, a crucial step in the dehydration of these toxic metabolites accumulating during cellular metabolism. This is the first report of a defect in the nicotinamide nucleotide repair system in humans.
    MeSH term(s) Carrier Proteins/genetics ; Female ; Homozygote ; Humans ; Infant ; Leukoencephalopathies/genetics ; Male ; Mutation ; Pedigree ; Siblings
    Chemical Substances Carrier Proteins ; NAXE protein, human (EC 5.1.-)
    Language English
    Publishing date 2016-04-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1339887-8
    ISSN 1364-6753 ; 1364-6745
    ISSN (online) 1364-6753
    ISSN 1364-6745
    DOI 10.1007/s10048-016-0483-3
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  8. Article ; Online: Clinical and molecular features in a cohort of Middle Eastern patients with epidermolysis bullosa.

    Bergson, Shir / Daniely, Daniel / Bomze, David / Mohamad, Janan / Malovitski, Kiril / Meijers, Odile / Briskin, Valeria / Bihari, Ofer / Malchin, Natalia / Israeli, Shirli / Mashiah, Jacob / Falik-Zaccai, Tzipora / Avitan-Hersh, Emily / Eskin-Schwartz, Marina / Allon-Shalev, Stavit / Sarig, Ofer / Sprecher, Eli / Samuelov, Liat

    Pediatric dermatology

    2023  Volume 40, Issue 6, Page(s) 1021–1027

    Abstract: Background: Epidermolysis bullosa (EB) features skin and mucosal fragility due to pathogenic variants in genes encoding components of the cutaneous basement membrane. Based on the level of separation within the dermal-epidermal junction, EB is sub- ... ...

    Abstract Background: Epidermolysis bullosa (EB) features skin and mucosal fragility due to pathogenic variants in genes encoding components of the cutaneous basement membrane. Based on the level of separation within the dermal-epidermal junction, EB is sub-classified into four major types including EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler EB (KEB) with 16 EB-associated genes reported to date.
    Methods: We ascertained a cohort of 151 EB patients of various Middle Eastern ethnic backgrounds.
    Results: The cohort was comprised of EBS (64%, 97/151), DEB (21%, 31/151), JEB (12%, 18/151), and KEB (3%, 5/151). KRT14 and KRT5 variants were most common among EBS patients with 43% (42/97) and 46% (45/97) of EBS patients carrying mutations in either of these two genes, respectively. Truncal involvement was more common in KRT14-associated EBS as compared to EBS due to KRT5 mutations (p < .05). Mutations in COL17A1 and laminin 332-encoding genes were identified in 55% (10/18) and 45% (8/18) of JEB patients. Scarring alopecia, caries, and EB nevi were most common among JEB patients carrying COL17A1 mutations as compared to laminin 332-associated JEB (p < .05). Abnormal nails were evident in most DEB and JEB patients while poikiloderma was exclusively observed in KEB (p < .001).
    Conclusions: EB patients of Middle Eastern origin were found to feature specific phenotype-genotype correlations of relevance to the diagnosis and genetic counseling of patients in this region.
    MeSH term(s) Humans ; Epidermolysis Bullosa/complications ; Epidermolysis Bullosa, Junctional/complications ; Epidermolysis Bullosa, Junctional/genetics ; Epidermolysis Bullosa, Junctional/pathology ; Epidermolysis Bullosa Dystrophica/complications ; Skin/pathology ; Epidermolysis Bullosa Simplex/genetics ; Epidermolysis Bullosa Simplex/complications
    Language English
    Publishing date 2023-10-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 605539-4
    ISSN 1525-1470 ; 0736-8046
    ISSN (online) 1525-1470
    ISSN 0736-8046
    DOI 10.1111/pde.15440
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  9. Article ; Online: Bi-allelic FRA10AC1 variants in a multisystem human syndrome.

    Banka, Siddharth / Shalev, Stavit / Park, Soo-Mi / Wood, Katherine A / Thomas, Huw B / Wright, Helen L / Alyahya, Mohammed / Bankier, Sean / Alimi, Ola / Chervinsky, Elena / Zeef, Leo A H / O'Keefe, Raymond T

    Brain : a journal of neurology

    2022  Volume 145, Issue 10, Page(s) e86–e89

    MeSH term(s) Humans ; Alleles ; Syndrome
    Language English
    Publishing date 2022-07-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 80072-7
    ISSN 1460-2156 ; 0006-8950
    ISSN (online) 1460-2156
    ISSN 0006-8950
    DOI 10.1093/brain/awac262
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  10. Article ; Online: A homozygous variant in

    Cohen-Barak, Eran / Danial-Farran, Nada / Chervinsky, Elana / Alimi-Kasem, Ola / Zagairy, Fadia / Livneh, Ido / Mawassi, Bannan / Hreish, Maysa / Khayat, Morad / Lossos, Alexander / Meiner, Vardiella / Ehilevitch, Nina / Weiss, Karin / Shalev, Stavit

    Journal of medical genetics

    2022  Volume 60, Issue 3, Page(s) 233–240

    Abstract: Background: Monogenic neurodegenerative diseases represent a heterogeneous group of disorders caused by mutations in genes involved in various cellular functions including autophagy, which mediates degradation of cytoplasmic contents by their transport ... ...

    Abstract Background: Monogenic neurodegenerative diseases represent a heterogeneous group of disorders caused by mutations in genes involved in various cellular functions including autophagy, which mediates degradation of cytoplasmic contents by their transport into lysosomes. Abnormal autophagy is associated with hereditary ataxia and spastic paraplegia, amyotrophic lateral sclerosis and frontal dementia, characterised by intracellular accumulation of non-degraded proteins. We investigated the genetic basis of complex HSP in a consanguineous family of Arab-Muslim origin, consistent with autosomal recessive inheritance.
    Methods: Exome sequencing was followed by variant filtering and Sanger sequencing for validation and familial segregation. Studies for mRNA and protein expression used real-time PCR and immunoblots. Patients' primary fibroblasts were analysed using electron microscopy, immunofluorescence, western blot analysis and ectopic plasmid expression for its impact on autophagy.
    Results: We identified a homozygous missense variant in
    Conclusions: Reduced level of CHMP3 is associated with complex spastic paraplegia phenotype, through aberrant autophagy mechanisms.
    MeSH term(s) Humans ; Spastic Paraplegia, Hereditary/genetics ; Proteins/genetics ; Paraplegia/genetics ; Mutation ; Autophagy ; Pedigree ; Endosomal Sorting Complexes Required for Transport/genetics
    Chemical Substances Proteins ; CHMP3 protein, human ; Endosomal Sorting Complexes Required for Transport
    Language English
    Publishing date 2022-06-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 220881-7
    ISSN 1468-6244 ; 0022-2593
    ISSN (online) 1468-6244
    ISSN 0022-2593
    DOI 10.1136/jmedgenet-2022-108508
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