Non-Type I Cystinuria Associated with Mental retardation and Ataxia in a Korean Boy with a New Missence Mutation(G173R) in the SLC7A9 Gene

Cystinuria is an inherited renal and intestinal disease characterized by defective amino acids reabsorption and cystine urolithiasis. It is unusually associated with neurologic symptoms. Mutations in two genes, SLC3A1 and SLC7A9, have been identified in cystinuric patients. This report presents a 13-yr-old boy with cystinuria who manifested difficulty in walking, ataxia, and mental retardation. Somatosensory evoked potential of posterior tibial nerve stimulation showed the central conduction dysfunction through the posterior column of spinal cord. He was diagnosed non-type I cystinuria by urinary amino acid analysis and oral cystine loading test. We screened him and his family for gene mutation by direct sequencing of SLC3A1 and SLC7A9 genes. In this patient, we identified new missence mutation G173R in SLC7A9 gene

Clinical and molecular characterization of cystinuria in a French cohort: relevance of assessing large-scale rearrangements and splicing variants.

Cystinuria is an autosomal recessive disorder of dibasic amino acid transport in the kidney and the intestine leading to increased urinary cystine excretion and nephrolithiasis. Two genes, SLC3A1 and SLC7A9, coding respectively for rBAT and b0,+AT, account for the genetic basis of cystinuria. This study reports the clinical and molecular characterization of a French cohort including 112 cystinuria patients and 25 relatives from 99 families. Molecular screening was performed using sequencing and Quantitative Multiplex PCR of Short Fluorescent Fragments analyses. Functional minigene-based assays have been used to characterize splicing variants. Eighty-eight pathogenic nucleotide changes were identified in SLC3A1 (63) and SLC7A9 (25) genes, of which 42 were novel. Interestingly, 17% (15/88) and 11% (10/88) of the total number of variants correspond, respectively, to large-scale rearrangements and splicing mutations. Functional minigene-based assays were performed for six variants located outside the most conserved sequences of the splice sites; three variants affect splice sites, while three others modify exonic splicing regulatory elements (ESR), in good agreement with a new in silico prediction based on ΔtESRseq values. This report expands the spectrum of SLC3A1 and SLC7A9 variants and supports that digenic inheritance is unlikely. Furthermore, it highlights the relevance of assessing large-scale rearrangements and splicing mutations to fully characterize cystinuria patients at the molecular level

Digenic inheritance and genetic modifiers

Digenic inheritance (DI) concerns pathologies with the simplest form of multigenic etiology, implicating more than 1 gene (and perhaps the environment). True DI is when biallelic or even triallelic mutations in 2 distinct genes, in cis or in trans, are necessary and sufficient to cause pathology with a defined diagnosis. In true DI, a heterozygous mutation in each of 2 genes alone is not associated with a recognizable phenotype. Well-documented diseases with true DI are so far rare and follow non-Mendelian inheritance. DI is also encountered when by serendipity, pathogenic mutations responsible for 2 distinct disease entities are co-inherited, leading to a mixed phenotype. Also, we can consider many true monogenic Mendelian conditions, which show impressively broad spectrum of phenotypes due to pseudo-DI, as a result of co-inheriting genetic modifiers (GMs). I am herewith reviewing examples of GM and embark on presenting some recent notable examples of true DI, with wider discussion of the literature. Undeniably, the advent of high throughput sequencing is bound to unravel more patients suffering with true DI conditions and elucidate many important GM, thus impacting precision medicine. - 2017 John Wiley & Sons A/S. Published by John Wiley & Sons LtdCyprus Research Promotion Foundation (co-funded by the European Regional Development Fund and the Republic of Cyprus), Grant/Award number: NEW INFRASTRUCTURE/STRATEGIC/0308/24 ; Republic of Cyprus; European Regional Development Fund. The work of Prof Deltas presented here was partly supported by the Cyprus Research Promotion Foundation through the grant NEW INFRASTRUCTURE/STRATEGIC/0308/24 (co-funded by the European Regional Development Fund and the Republic of Cyprus).Scopu

Giving the Power to Bilingual Speakers

ing of the source language sentence is fully captured by the gold standard translation. For language pairs with a large number of speakers, and certainly for the pairs researchers are working on for GALE (Olive, 2005), Chinese-English and Arabic-English, it would certainly be easier to get bilingual speakers to be post-editors, than having to generate a gold standard for each translation. In this context, I use the term bilingual speaker loosely. When I say bilingual speakers, I do not mean people that were born and raised bilingually and have native skills in both languages, but rather people that are native in one of the two languages and are fluent in the second language. A good example of what I mean by bilingual speakers here could be second generation Chinese and Arabic people that were born and live in the United States or another Englishspeaking country. At this point, I would like to propose a new bilingual post-editing paradigm, one where post-editing does not have to be

Error Analysis of Two Types of Grammar for the Purpose of Automatic Rule Refinement

This paper compares a manually written MT grammar and a grammar learned automatically from an English-Spanish elicitation corpus with the ultimate purpose of automatically refining the translation rule

A Trainable Transfer-based Machine Translation Approach for Languages with Limited Resources

We describe a Machine Translation (MT) approach that is specifically designed to enable rapid development of MT for languages with limited amounts of online resources. Our approach assumes the availability of a small number of bi-lingual speakers of the two languages, but these need not be linguistic experts. The bi-lingua

Experiments with a Hindi-to-English Transfer-based MT System under a Miserly Data Scenario

We describe an experiment designed to evaluate the capabilities of our trainable transfer-based (Xfer) machine translation approach, as applied to the task of Hindi-to-English translation, and trained under an extremely limited data scenario. We compare the performance of the Xfer approach with two corpus-based approaches – Statistical MT (SMT) and Example-based MT (EBMT) – under the limited data scenario. The results indicate that the Xfer system significantly outperforms both EBMT and SMT in this scenario. Results also indicate that automatically learned transfer rules are effective in improving translation performance, compared with a baseline word-to-word translation version of the system. Xfer system performance with a limited number of manually written transfer rules is, however, still better than the current automatically inferred rules. Furthermore, a “multi-engine ” version of our system that combined the output of the Xfe