Leah Rizel

Publications (5)19.56 Total impact

• Source

  Available from: Eedy Mezer

  Article: Novel mutations of MYO7A and USH1G in Israeli Arab families with Usher syndrome type 1.

  Leah Rizel, Christine Safieh, Stavit A Shalev, Eedy Mezer, Haneen Jabaly-Habib, Ziva Ben-Neriah, Elena Chervinsky, Daniel Briscoe, Tamar Ben-Yosef
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  ABSTRACT: This study investigated the genetic basis for Usher syndrome type 1 (USH1) in four consanguineous Israeli Arab families. Haplotype analysis for all known USH1 loci was performed in each family. In families for which haplotype analysis was inconclusive, we performed genome-wide homozygosity mapping using a single nucleotide polymorphism (SNP) array. For mutation analysis, specific primers were used to PCR amplify the coding exons of the MYO7A, USH1C, and USH1G genes including intron-exon boundaries. Mutation screening was performed with direct sequencing. A combination of haplotype analysis and genome-wide homozygosity mapping indicated linkage to the USH1B locus in two families, USH1C in one family and USH1G in another family. Sequence analysis of the relevant genes (MYO7A, USH1C, and USH1G) led to the identification of pathogenic mutations in all families. Two of the identified mutations are novel (c.1135-1147dup in MYO7A and c.206-207insC in USH1G). USH1 is a genetically heterogenous condition. Of the five USH1 genes identified to date, USH1C and USH1G are the rarest contributors to USH1 etiology worldwide. It is therefore interesting that two of the four Israeli Arab families reported here have mutations in these two genes. This finding further demonstrates the unique genetic structure of the Israeli population in general, and the Israeli Arab population in particular, which due to high rates of consanguinity segregates many rare autosomal recessive genetic conditions.
  Molecular vision 01/2011; 17:3548-55. · 2.20 Impact Factor
• Article: Mutations in C2ORF71 cause autosomal-recessive retinitis pigmentosa.

  Rob W J Collin, Christine Safieh, Karin W Littink, Stavit A Shalev, Hanna J Garzozi, Leah Rizel, Anan H Abbasi, Frans P M Cremers, Anneke I den Hollander, B Jeroen Klevering, Tamar Ben-Yosef
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  ABSTRACT: With a worldwide prevalence of 1 in 4,000, retinitis pigmentosa (RP) is the most common form of hereditary retinal degeneration. More than 30 genes and loci have been implicated in nonsyndromic autosomal-recessive (ar) RP. Genome-wide homozygosity mapping was conducted in one Dutch and one Israeli family affected by arRP. The families were found to share a 5.9 Mb homozygous region on chromosome 2p23.1-p23.3. A missense variant in one of the genes residing in this interval, C2ORF71, has recently been reported to be associated with RP. C2ORF71, encoding a putative protein of 1,288 amino acids, was found to be specifically expressed in human retina. Furthermore, RT-PCR analysis revealed that in the mouse eye, C2orf71 is expressed as early as embryonic day 14. Mutation analysis detected a 1 bp deletion (c.946 del; p.Asn237MetfsX5) segregating with RP in the Dutch family, whereas a nonsense mutation (c.556C > T; p.Gln186X) was identified in the Israeli family. Microsatellite-marker analysis in additional Israeli families revealed cosegregation of a C2ORF71-linked haplotype in one other family, in which a 13 bp deletion (c.2756_2768 del; p.Lys919ThrfsX) was identified. Clinically, patients with mutations in C2ORF71 show signs of typical RP; these signs include poor night vision and peripheral field loss, typical retinal bone-spicule-type pigment deposits, pale appearance of the optic disk, and markedly reduced or completely extinguished electroretinograms. In conclusion, truncating mutations in C2ORF71 were identified in three unrelated families, thereby confirming the involvement of this gene in the etiology of arRP.
  The American Journal of Human Genetics 05/2010; 86(5):783-8. · 10.60 Impact Factor
• Article: Genetic heterogeneity in two consanguineous families segregating early onset retinal degeneration: the pitfalls of homozygosity mapping.

  Liat Benayoun, Ronen Spiegel, Noa Auslender, Anan H Abbasi, Leah Rizel, Yasir Hujeirat, Ihsan Salama, Hanna J Garzozi, Stavit Allon-Shalev, Tamar Ben-Yosef
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  ABSTRACT: Retinitis pigmentosa is the most common form of hereditary retinal degeneration, with a worldwide prevalence of 1 in 4,000. At least 28 genes and loci have been implicated in nonsyndromic autosomal recessive retinitis pigmentosa. Here we report two extended and highly consanguineous families segregating early onset retinitis pigmentosa. Despite the consanguinity in both families, we found allelic heterogeneity in one of them, in which affected individuals were compound heterozygotes for two different mutations of the CRB1 gene. In the second family we found evidence for locus heterogeneity. A novel homozygous mutation of RDH12 was found in only 14 of 17 affected individuals in this family. Our data indicate that in the other affected individuals the disease is caused by a different gene/s. These findings demonstrate that while homozygosity mapping is an efficient tool for identification of the underlying mutated genes in inbred families, both locus and allelic heterogeneity may occur even within the same consanguineous family. These observations should be taken into account, especially when studying common and heterogeneous recessive genetic conditions.
  American Journal of Medical Genetics Part A 02/2009; 149A(4):650-6. · 2.39 Impact Factor
• Article: Four USH2A founder mutations underlie the majority of Usher syndrome type 2 cases among non-Ashkenazi Jews.

  Noa Auslender, Dikla Bandah, Leah Rizel, Doron M Behar, Mordechai Shohat, Eyal Banin, Stavit Allon-Shalev, Reuven Sharony, Dror Sharon, Tamar Ben-Yosef
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  ABSTRACT: Type 2 Usher syndrome (USH2) is a recessively inherited disorder, characterized by the combination of early onset, moderate-to-severe, sensorineural hearing loss, and vision impairment due to retinitis pigmentosa. From 74% to 90% of USH2 cases are caused by mutations of the USH2A gene. USH2A is composed of 72 exons, encoding for usherin, an extracellular matrix protein, which plays an important role in the development and maintenance of neurosensory cells in both retina and cochlea. To date, over 70 pathogenic mutations of USH2A have been reported in individuals of various ethnicities. Many of these mutations are rare private mutations segregating in single families. The aim of the current work was to investigate the genetic basis for USH2 among Jews of various origins. We found that four USH2A mutations (c.239-240insGTAC, c.1000C>T, c.2209C>T, and c.12067-2A>G) account for 64% of mutant alleles underlying USH2 in Jewish families of non-Ashkenazi descent. Considering the very large size of the USH2A gene and the high number of mutations detected in USH2 patients worldwide, our findings have significant implications for genetic counseling and carrier screening in various Jewish populations.
  Genetic Testing 06/2008; 12(2):289-94. · 1.17 Impact Factor
• Article: Abetalipoproteinemia in Israel: evidence for a founder mutation in the Ashkenazi Jewish population and a contiguous gene deletion in an Arab patient.

  Liat Benayoun, Esther Granot, Leah Rizel, Stavit Allon-Shalev, Doron M Behar, Tamar Ben-Yosef
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  ABSTRACT: Abetalipoproteinemia (ABL) is a rare autosomal recessive metabolic disorder, characterized by the absence of plasma apolipoprotein B-containing lipoproteins and very low levels of plasma triglycerides and cholesterol. ABL is caused by mutations of the MTP gene. We investigated the genetic basis for ABL in a cohort of Israeli families. In Ashkenazi Jewish patients we identified a conserved haplotype and a common MTP mutation, p.G865X, with a carrier frequency of 1:131 in this population. We also report the first case of ABL and additional abnormalities in a Muslim Arab patient, due to a homozygous contiguous gene deletion of approximately 481 kb, including MTP and eight other genes.
  Molecular Genetics and Metabolism 05/2007; 90(4):453-7. · 3.19 Impact Factor