Changes in Marriage Patterns Among the Arab Community in Israel Over a 60-Year Period

Sharkia, Rajech; Mahajnah, Muhammad; Athamny, Esmael; Khatib, Mohammad; Ahmad, Shahzad; Zalan, Abdelnaser

doi:10.1017/s0021932015000103

Cited by 19 publications

(11 citation statements)

References 10 publications

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“…Of note, although they are not related to the previously eight reported patients, they live in the same town from which patients I1 to I5 originated. This town comprising about 50 000 inhabitants and is known for its very high (around 45%) consanguinity rate predicting a relatively high carrier rate for this mutation. Noteworthy, the c.336C>G mutation carrier rate in this town was calculated to be 1% not justifying a prenatal couple screening in this population (Spiegel et al unpublished data).…”

Section: Resultsmentioning

confidence: 99%

Clinical, radiological, and genetic characteristics of 16 patients with ACO2 gene defects: Delineation of an emerging neurometabolic syndrome

Sharkia

Wierenga

Kessel

et al. 2019

J of Inher Metab Disea

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Mitochondrial aconitase is the second enzyme in the tricarboxylic acid (TCA) cycle catalyzing the interconversion of citrate into isocitrate and encoded by the nuclear gene ACO2. A homozygous pathogenic variant in the ACO2 gene was initially described in 2012 resulting in a novel disorder termed “infantile cerebellar retinal degeneration” (ICRD, OMIM#614559). Subsequently, additional studies reported patients with pathogenic ACO2 variants, further expanding the genetic and clinical spectrum of this disorder to include milder and later onset manifestations. Here, we report an international multicenter cohort of 16 patients (of whom 7 are newly diagnosed) with biallelic pathogenic variants in ACO2 gene. Most patients present in early infancy with severe truncal hypotonia, truncal ataxia, variable seizures, evolving microcephaly, and ophthalmological abnormalities of which the most dominant are esotropia and optic atrophy with later development of retinal dystrophy. Most patients remain nonambulatory and do no acquire any language, but a subgroup of patients share a more favorable course. Brain magnetic resonance imaging (MRI) is typically normal within the first months but global atrophy gradually develops affecting predominantly the cerebellum. Ten of our patients were homozygous to the previously reported c.336C>G founder mutation while the other six patients were all compound heterozygotes displaying 10 novel mutations of whom 2 were nonsense predicting a deleterious effect on enzyme function. Structural protein modeling predicted significant impairment in aconitase substrate binding in the additional missense mutations. This study provides the most extensive cohort of patients and further delineates the clinical, radiological, biochemical, and molecular features of ACO2 deficiency.

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Section: Resultsmentioning

confidence: 99%

Clinical, radiological, and genetic characteristics of 16 patients with ACO2 gene defects: Delineation of an emerging neurometabolic syndrome

Sharkia

Wierenga

Kessel

et al. 2019

J of Inher Metab Disea

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“…The major challenge for this platform is rare variant filtering, which is markedly alleviated when the patient is the product of a consanguineous marriage, as only homozygous variants are retained. Consanguinity is practiced by approximately 20% of the human population and amounts to 31% among Israeli Arabs 23 and 40% among Palestinian Arabs. 24 Since 2011, we have performed 1800 exome analyses, of which~1500 were singleton.…”

Section: Discussionmentioning

confidence: 99%

tRNA N6-adenosine threonylcarbamoyltransferase defect due to KAE1/TCS3 (OSGEP) mutation manifest by neurodegeneration and renal tubulopathy

et al. 2017

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Post-transcriptional tRNA modifications are numerous and require a large set of highly conserved enzymes in humans and other organisms. In yeast, the loss of many modifications is tolerated under unstressed conditions; one exception is the N-threonyl-carbamoyl-adenosine (tA) modification, loss of which causes a severe growth phenotype. Here we aimed at a molecular diagnosis in a brother and sister from a consanguineous family who presented with global developmental delay, failure to thrive and a renal defect manifesting in proteinuria and hypomagnesemia. Using exome sequencing, the patients were found to be homozygous for the c.974G>A (p.(Arg325Gln)) variant of the KAE1 gene. KAE1 is a constituent of the KEOPS complex, a five-subunit complex that catalyzes the second biosynthetic step of tA in the cytosol. The yeast KAE1 allele carrying the equivalent mutation did not rescue the tA deficiency of the kae1Δ yeast strain as efficiently as the WT allele; furthermore, tA levels quantified by LC-MS/MS were lower in the kae1Δ strain which was complemented by the mutation than in the kae1Δ strain, which was complemented by the WT allele. We conclude that homozygosity for c.974G>A (p.(Arg325Gln)) in KAE1 likely exerts its pathogenic effect by perturbing tA synthesis, thereby interfering with global protein production. This is the first report of tA biosynthesis defect in human. KAE1 joins the growing list of cytoplasmic tRNA modification enzymes, all associated with severe neurological disorders.

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“…The evidence for a decline in consanguineous marriage has been accumulating (Jaber, Halpern, and Shohat 2000;Vardi-Saliternik, Friedlander, and Cohen 2002;Kenan and Burck 2002;Sharkia et al 2008;Na'amnih et al 2015). Using a representative sample of more than 3,000 couples that married between 1948 and 2007, Sharkia et al (2016) estimate that the percentage in a consanguineous marriage started to decline after 1980.…”

Section: Datamentioning

confidence: 99%

The decline in consanguineous marriage among Muslims in Israel: The role of education

Schellekens¹,

Kenan²,

Hleihel³

2017

DemRes

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Changes in Marriage Patterns Among the Arab Community in Israel Over a 60-Year Period

Cited by 19 publications

References 10 publications

Clinical, radiological, and genetic characteristics of 16 patients with ACO2 gene defects: Delineation of an emerging neurometabolic syndrome

Clinical, radiological, and genetic characteristics of 16 patients with ACO2 gene defects: Delineation of an emerging neurometabolic syndrome

tRNA N6-adenosine threonylcarbamoyltransferase defect due to KAE1/TCS3 (OSGEP) mutation manifest by neurodegeneration and renal tubulopathy

The decline in consanguineous marriage among Muslims in Israel: The role of education

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