Abstract:
:Donohue syndrome (DS) is a rare and lethal autosomal recessive disease caused by mutations in the insulin receptor (INSR) gene, manifesting marked insulin resistance, severe growth retardation, hypertrichosis, and characteristic dysmorphic features. We report the clinical, molecular, and biochemical characterization of three new patients with DS, and address genotype-phenotype issues playing a role in the pathophysiology of DS. A female infant born to first-degree cousins Muslim Arab parents and two brothers born to first-degree cousins Druze parents presented classical features of DS with hypertrophic cardiomyopathy and died in infancy. Each patient was found homozygous for one missense mutation within the extracellular domain of the INSR gene. Western blot analysis identified the proreceptor of INSR, but not its mature subunits alpha and beta. Of 95 healthy Muslims, no heterozygous was found and of 52 healthy Druze from the same village, one was heterozygous. This study presents two novel familial mutations in the alpha subunit of the INSR which appear to impair post-translational processing of the INSR, resulting loss of its function. Both mutations cause DS with hypertrophic cardiomyopathy and early death. Identification of the causative mutation enables prevention of this devastating disease.
journal_name
Mol Genet Genomic Medjournal_title
Molecular genetics & genomic medicineauthors
Falik Zaccai TC,Kalfon L,Klar A,Elisha MB,Hurvitz H,Weingarten G,Chechik E,Fleisher Sheffer V,Haj Yahya R,Meidan G,Gross-Kieselstein E,Bauman D,Hershkovitz S,Yaron Y,Orr-Urtreger A,Wertheimer Edoi
10.1002/mgg3.43subject
Has Abstractpub_date
2014-01-01 00:00:00pages
64-72issue
1issn
2324-9269journal_volume
2pub_type
杂志文章abstract:BACKGROUND:Bicuspid aortic valve (BAV) is the most common congenital heart defect with a prevalence of 1%-2% in the general population. NOTCH1, SMAD6, and GATA5 are associated with BAV in humans, but few cases have been reported that did not involve NOTCH1. Here, we identified novel in-frame variants in SMAD6 (c.1168_1...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.291
更新日期:2017-04-23 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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更新日期:2020-01-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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更新日期:2017-01-26 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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更新日期:2018-05-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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更新日期:2020-10-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.335
更新日期:2017-11-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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更新日期:2020-02-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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更新日期:2020-09-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1304
更新日期:2020-08-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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更新日期:2019-11-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.958
更新日期:2019-11-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.23
更新日期:2013-11-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1022
更新日期:2019-12-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1557
更新日期:2020-11-25 00:00:00
abstract:BACKGROUND:Alcohol-induced osteonecrosis of femoral head (ONFH) is a complex disease and genetic factors are one of the causes. The purpose of this study is to investigate the effects of RETN (resistin; OMIM: 605565) and LDLR (low density lipoprotein receptor; OMIM: 606945) polymorphisms on the risk of alcohol-induced ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.822
更新日期:2019-08-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.774
更新日期:2019-08-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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更新日期:2019-05-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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更新日期:2020-06-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.965
更新日期:2019-10-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1004
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND:Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by functional impairment of cilia throughout the body. The involvement of copy number variation (CNV) in the development of PCD is largely unknown. METHODS:We examined 93 Japanese patients with clinically suspected PCD from 84 unrelated fami...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
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更新日期:2020-03-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1316
更新日期:2020-08-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.1403
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:Beta-propeller protein-associated neurodegeneration (BPAN, OMIM 300894) is an X-linked neurodegenerative disorder caused by mutations in WDR45. WDR45 is required for autophagy, defect in WDR45 impaired autophagy which contributes for the pathogenesis of BPAN. Previously, we reported a novel de novo mutation ...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.858
更新日期:2019-09-01 00:00:00
abstract::In this letter, we want to add information to the paper "Genetics and genomic medicine in Argentina" that we considered it was lacking. Argentina is a big country with inequalities in the access to public health care, especially in medical genetics and genomics. ...
journal_title:Molecular genetics & genomic medicine
pub_type: 评论,信件
doi:10.1002/mgg3.571
更新日期:2019-04-01 00:00:00
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journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章,评审
doi:10.1002/mgg3.997
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND:With the availability of raw DNA generated from direct-to-consumer (DTC) testing companies, there has been a proliferation of third-party online services that are available to interpret the raw data for both genealogy and/or health purposes. This study examines the current landscape and downstream clinical i...
journal_title:Molecular genetics & genomic medicine
pub_type: 杂志文章
doi:10.1002/mgg3.340
更新日期:2018-01-01 00:00:00