Lior Cohen's research while affiliated with Ben-Gurion University of the Negev and other places

Publications (15)

Article
Purpose: KLHL20 is part of a CUL3-RING E3 ubiquitin ligase involved in protein ubiquitination. KLHL20 functions as the substrate adaptor that recognizes substrates and mediates the transfer of ubiquitin to the substrates. Although KLHL20 regulates neurite outgrowth and synaptic development in animal models, a role in human neurodevelopment has not...
Article
Full-text available
Mendelian disorders of the epigenetic machinery (MDEMs), also named chromatin modifying disorders, are a broad group of neurodevelopmental disorders, caused by mutations in functionally related chromatin genes. Mental retardation autosomal dominant 23 (MRD23) syndrome, due to SETD5 gene mutations, falls into this group of disorders. KBG syndrome, c...
Article
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Sifrim–Hitz–Weiss syndrome (SIHIWES) is a recently described multisystemic neurodevelopmental disorder caused by de novo variants in CHD4. In this study, we investigated the clinical spectrum of the disorder, genotype–phenotype correlations, and the effect of different missense variants on CHD4 function. We collected clinical and molecular data fro...
Article
Majewski Osteodysplastic Primordial Dwarfism type II (MOPDII) is a form of dwarfism associated with severe microcephaly, characteristic skeletal findings, distinct dysmorphic features and increased risk for cerebral infarctions. The condition is caused by bi-allelic loss-of-function variants in the gene PCNT. Here we describe the identification of...
Article
Background: We describe the ophthalmologic, clinical, and genetic findings in a patient of Yemenite-Jewish origin diagnosed with Alstrom syndrome due to a novel splice-site mutation 10 years after a clinical misdiagnosis of Leber congenital amaurosis. Methods: Ophthalmological evaluations included visual acuity, cycloplegic refraction, slit-lamp, a...
Article
Herein, we describe two members of one family who presented with recurrent episodes of hepatic failure, cerebellar ataxia, peripheral neuropathy, and short stature. Liver transplantation was considered. Whole-exome sequencing (Trio) revealed a synonymous variant in exon 4 of SCYL1:c.459C>T p. (Gly153Gly), which did not appear to affect the protein...
Article
Introduction: Whole exome sequencing is a diagnostic approach for the identification of molecular etiology in patients with suspected monogenic diseases. In this article we report on our experience with whole-exome sequencing (WES) of DNA samples taken from patients referred for genetic evaluation due to suspected undiagnosed genetic conditions....
Article
Metaphyseal anadysplasia (MANDP) is a rare autosomal recessive form of skeletal dysplasia characterized by normal length at birth and transitory bowing of the legs. Although several families with MANDP have been reported, homozygous mutations in the matrix metalloproteinase type 9 (MMP9) gene have been described in only one consanguineous family, a...
Article
Context: Primary ovarian insufficiency (POI) is caused by ovarian follicle depletion or follicle dysfunction, characterized by amenorrhea with elevated gonadotropin levels. The disorder presents as absence of normal progression of puberty. Objective: To elucidate the cause of ovarian dysfunction in a family with POI. Design: We performed whole...
Article
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Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATP-dependent chromatin remodeler involved in epigenetic regulation of gene transcription, DNA repair, and cell cycle progression. Also known as Mi2β, CHD4 is an integral subunit of a well-characterized histone deacetylase complex. Here we report five individuals with de novo missense substit...
Article
Inherited optic neuropathies are a heterogeneous group of disorders characterized by mild to severe visual loss, colour vision deficit, central or paracentral visual field defects and optic disc pallor. Optic atrophies can be classified into isolated or non-syndromic and syndromic forms. While multiple modes of inheritance have been reported, autos...
Article
One of the goals of evaluating a patient in the genetics clinic is to find the diagnosis that would explain his or her clinical presentation. Sometimes the patient's diagnosis remains undefined or does not explain all of the clinical findings. As clinicians are often guided by a "single disorder" paradigm, diagnosing multiple genetic conditions in...
Article
We describe a Bedouin family with a novel autosomal recessive syndrome characterized by dilated cardiomyopathy and septo-optic dysplasia. Genetic analysis revealed a homozygous missense mutation in TAX1BP3, which encodes a small PDZ-containing protein implicated in regulation of the Wnt/β-catenin signaling pathway, as the causative mutation. The mu...
Article
Keppen-Lubinsky syndrome (KPLBS) is a rare disease mainly characterized by severe developmental delay and intellectual disability, microcephaly, large prominent eyes, a narrow nasal bridge, a tented upper lip, a high palate, an open mouth, tightly adherent skin, an aged appearance, and severe generalized lipodystrophy. We sequenced the exomes of th...

Citations

... In addition, a patient carrying ANKRD11 deletion, with normal psychomotor development and clinical signs reminiscent of the Silver-Russell syndrome ((SRS; OMIM#180860), has been reported [10]. The diagnosis is even more arduous since several neurodevelopmental disorders such as the Cornelia de Lange (CdLS; OMIM#122470), Coffin-Siris (CSS; OMIM#135900), and Mental Retardation Autosomal Dominant 23 (MRD23; OMIM#615761) syndromes share some phenotypic features with KBGS, including a variable degree of intellectual disability and developmental delay, growth retardation, and common facial dysmorphisms [11][12][13][14]. This phenotypic overlap appears to reflect the molecular interaction of the causative genes of these syndromes, all acting as chromatin modifiers in common cellular mechanisms and pathways [15]. ...
... 8. ATP1B1 : intellectual disability & self-mutilation (Liu et al., 2015), autism (Iossifov et al., 2012;Iossifov et al., 2014;Uddin et al., 2014), autism spectrum disorder Turner et al., 2019), intellectual disability (Liu et al., 2015), schizophrenia (Purcell et al., 2014) 9. CHD3 Yuen et al., 2016;Kosmicki et al., 2017;Turner et al., 2019), autism spectrum disorder (Wang et al., 2016;Cappi et al., 2020;Satterstrom et al., 2020) 10. CHD4 : Sifrim-Hitz-Weiss syndrome (Weiss et al., 2020), neurodevelopmental disorder (Trinh et al., 2019), intellectual disability (Weiss et al., 2016(Weiss et al., , 2020, developmental disorder (Deciphering Developmental Disorders, 2017;Turner et al., 2019;Weiss et al., 2020), autism spectrum disorder Wang et al., 2016;Kosmicki et al., 2017), intellectual disability, macrocephaly, hyperlaxity of finger joints and hearing loss (Monroe et al., 2016;Weiss et al., 2016), schizophrenia (Girard et al., 2011;Li et al., 2016) The candidacy of these genes was justified by their genomic positions in CNV mapping, sporadic variants reported in them and their interactors in NDDs, their physical interaction with known neurodevelopmental genes, and KO mice phenotype based on HGMD, BioGrid, STRING, and MGI. Due to a large number of interacting genes, only a limited number of them in NDD were described. ...
... Especialmente la proteína de unión a DNA con cromodominio helicasa CHD4 promueve la proliferación de los precursores neurales. La pérdida de función en CHD4 se asocia a retraso del desarrollo psicomotor, trastornos de lenguaje y discapacidad intelectual variable, descrito en el síndrome de Sifrim-Hitz-Weiss 43 . Por último, las variantes de histonas H2A.Z y H3.3 tienen funciones especializadas en la regulación del linaje neural durante el periodo embrionario 32 . ...
... The Druze community encompasses 1.6% of the Israeli population and is characterized by consanguinity and endogamy. There is a great reluctance in this population to undergo genetic testing and technological interventions in preventin birth defects [3][4][5]. For example, cases such as multiple patients with four rare and severe inborn errors of metabolism cerebrotendinous xanthomatosis, prolidase deficiency, argininosuccinate lyase deficiency, and carbamyl phosphate synthetase I deficiency were identified in an isolated Druze village in northern Israel [3]. ...
... Thus far, nearly 700 cases have been described worldwide. In addition, AS patients may experience absence seizures and general sleep disturbance (5,22,23), as was observed in our patient, who has had episodes of epilepsy seizures at two years old and had been experiencing learning difficulties in school. ...
... Scyl1 mdf mutant mice display motor neuron disorders recapitulating most human amyotrophic lateral sclerosis (ALS) symptoms 28 . Moreover, loss of function mutations of human SCYL1 are associated with multiple recessive hereditary disorders that have been grouped under the term cholestasis, acute liver failure, and neurodegeneration (CALFAN) syndrome [29][30][31][32][33] . The syndrome has also been recently associated with recurrent respiratory failure 33 . ...
... Protein expression occurs as selective nuclear and cytoplasmic expression in proximal tubules of kidney, cells in the red and white pulp of the spleen, hematopoietic cells of bone marrow, preleptotene spermatocytes and the spermatogonia cells of the testis and non-germinal center cells of the appendix, lymph nodes and tonsils [19]. The literature contains examples of disorders involving the mutation of the MMP gene, including metaphyseal anadysplasia in which it occurs together with the MMP-13 gene [26,27]. As in the case of MMP-2, here the functional polymorphism of the MMP-9 s gene locus occupies the position on the chromosome 20q11.2-q13.1. ...
... 56 It is interesting to note that genes belonging to the meiosis/DNA repair family including genes of the synaptonemal complex is the leading family shared by POI and male infertility with azoospermia. This is the case for novel variants in genes identified in our study: STAG3, 58À60 SPIDR, 8,56,61 PSMC3IP, 62,63 HFM1, 56,64 FANCM. 9, 65 We can therefore expect the discovery of other genes causing both male and female infertility in the near future, belonging especially to the meiosis and DNA repair gene family. ...
... CHD4 gene encodes chromodomain helicase DNA-binding protein 4 (CHD4), which belongs to the SNF2/RAD54 helicase family. It is an ATP-dependent chromatin remodeler that is involved in epigenetic regulation of gene transcription, DNA repair, and cell cycle progression [164]. Four novel CHD4 mutations, including two de novo mutations (c.1597A > G/p.K533E and c.4936G > A/p.E1646K) and two inherited mutations with co-segregation (c.856C > G/p. ...