Expanding the clinical, allelic, and locus heterogeneity of retinal dystrophies
| Autor: | Ali Alasmari, Bandar Al-Saud, Yong Xiong, Emad B. Abboud, Banan Al-Younes, Abeer Al-Mostafa, Ranad Shaheen, Abdulelah AlIssa, Ewa A. Naim, Mohammed A. Aldahmesh, Dorota Monies, Olga Buzovetsky, Niema Ibrahim, Mohamed Abouelhoda, Nada Al-Tassan, Ghada M H Abdel-Salam, Saleh Al-mohsen, Hisham Alkuraya, Hadeel Alsharif, Mohammed Al-Owain, Arif O. Khan, Asma Sunker, Mais Hashem, Sawsan R. Nowilaty, Selwa A.F. Al-Hazzaa, Firdous Abdulwahab, Shamsa Anazi, Hamad Al-Zaidan, Nisha Patel, Fowzan S. Alkuraya |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male Mucopolysaccharidosis Carboxypeptidases Mitochondrial Membrane Transport Proteins Retina Hypogammaglobulinemia 03 medical and health sciences Locus heterogeneity Retinitis pigmentosa Retinal Dystrophies Exome Sequencing Medicine Humans Allele Genetics (clinical) Exome sequencing Genetics business.industry Homozygote medicine.disease Cadherins Pedigree 030104 developmental biology Phenotype Mutation (genetic algorithm) Mutation Female business |
| Zdroj: | Genetics in medicine : official journal of the American College of Medical Genetics. 18(6) |
| ISSN: | 1530-0366 |
| Popis: | Retinal dystrophies (RD) are heterogeneous hereditary disorders of the retina that are usually progressive in nature. The aim of this study was to clinically and molecularly characterize a large cohort of RD patients. We have developed a next-generation sequencing assay that allows known RD genes to be sequenced simultaneously. We also performed mapping studies and exome sequencing on familial and on syndromic RD patients who tested negative on the panel. Our panel identified the likely causal mutation in >60% of the 292 RD families tested. Mapping studies on all 162 familial RD patients who tested negative on the panel identified two novel disease loci on Chr2:25,550,180-28,794,007 and Chr16:59,225,000-72,511,000. Whole-exome sequencing revealed the likely candidate as AGBL5 and CDH16, respectively. We also performed exome sequencing on negative syndromic RD cases and identified a novel homozygous truncating mutation in GNS in a family with the novel combination of mucopolysaccharidosis and RD. Moreover, we identified a homozygous truncating mutation in DNAJC17 in a family with an apparently novel syndrome of retinitis pigmentosa and hypogammaglobulinemia. Our study expands the clinical and allelic spectrum of known RD genes, and reveals AGBL5, CDH16, and DNAJC17 as novel disease candidates. Genet Med 18 6, 554–562. |
| Databáze: | OpenAIRE |
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