Pía Villanueva

Genome-wide analysis of genetic susceptibility to language impairment in an isolated Chilean population.

Specific language impairment (SLI) is an unexpected deficit in the acquisition of language skills and affects between 5 and 8% of pre-school children. Despite its prevalence and high heritability, our understanding of the aetiology of this disorder is only emerging. In this paper, we apply genome-wide techniques to investigate an isolated Chilean population who exhibit an increased frequency of SLI. Loss of heterozygosity (LOH) mapping and parametric and non-parametric linkage analyses indicate that complex genetic factors are likely to underlie susceptibility to SLI in this population. Across all analyses performed, the most consistently implicated locus was on chromosome 7q. This locus achieved highly significant linkage under all three non-parametric models (max NPL=6.73, P=4.0 × 10−11). In addition, it yielded a HLOD of 1.24 in the recessive parametric linkage analyses and contained a segment that was homozygous in two affected individuals. Further, investigation of this region identified a two-SNP haplotype that occurs at an increased frequency in language-impaired individuals (P=0.008). We hypothesise that the linkage regions identified here, in particular that on chromosome 7, may contain variants that underlie the high prevalence of SLI observed in this isolated population and may be of relevance to other populations affected by language impairments.

Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment

Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10–4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model.

Association of D16S515 Microsatellite with Specific Language Impairment on Robinson Crusoe Island, an Isolated Chilean Population: A Possible Key to Understanding Language Development

Abstract Specific language impairment (SLI) is a developmental language disorder that occurs for no known reason. The disorder affects 2–8% of children. Some scientific evidence suggests that genetic factors are implicated in the etiology of SLI. The disorder is genetically complex. Two novel loci, SLI1 on chromosome 16q24 (MIM 606711) and SLI2 on chromosome 19q13 (MIM 606712), have been found to be highly correlated with SLI. Four genes have been identified as susceptibility genes. SLI occurs at an unusually elevated incidence (35%) among the population of Robinson Crusoe Island (Chile), which also has a high consanguinity rate. This finding supports the influence of genetic mechanisms in the transmission of SLI based on a founder effect. To investigate further the genetic involvement in this population, we collected blood samples from 115 islanders from 13 families with a language-impaired proband and from 18 families with a normal-language proband. The analysis of micro satellite marker D16S515, located in locus SLI1, demonstrated that the 230-bp allele was correlated with SLI and that the 232-bp allele was correlated with normal language development. The domain containing the D16S515 marker, therefore, may play a role in language development.

Consanguinity on Robinson Crusoe Island, an isolated Chilean population.

The population of Robinson Crusoe Island is estimated at 633 inhabitants. The current population has a common origin from the first eight families who colonized the island at the end of the 19th century. The objective of this study was to determine the rates of consanguinity, the average coefficients of inbreeding, the types of consanguineous marriages and the inbreeding evolution between 1900 and 2000 on the island. All marriages registered on the island, from the last colonization until 2000 (417 in total), were included in the analysis. In addition, extended genealogies were obtained. The consanguinity rate was 14.9% and the average coefficient of inbreeding (α) 54.05 × 10(-4). The most frequent type of consanguineous marriages was between second cousins, followed by first cousins. The average value of the first/second cousin ratio was 1.11. The population of Robinson Crusoe Island has a high rate of inbreeding. The unique characteristic of the island - its small current population, originating from just a few families, with small rate of gene flow - could explain the observed high and increasing consanguinity.

Modificaciones en la articulación de fones en pacientes con aparato ortodóncico fijo lingual

PURPOSE: this study evaluated the effect of lingual orthodontics appliances on speech performance in native Chilean spanish speakers, and their adaptation to these effects during the first month. METHODS: phone production was recorded in a standardized test, in 13 patients with lingual orthodontic brackets, in 5 different times: before (E0), immediately after (E1), within 24 hours after (E2), within 7 days after (E3) and 1 month after (E4) the placement of fixed orthodontic lingual appliances, for assessment by speech professionals. RESULTS: statistically significant changes were observed in the articulation of [d], [s] and [r] phones. Sounds [d] and [s] showed an improvement within first month of use of the appliances. Phone alveolar vibrant [r] did not show a significant reduce of sound impairment performance. CONCLUSION: lingual appliances placement induce impairment in sound performance but these changes show an improvement within the first month of use, with exception of alveolar vibrant [r] phone.

Parámetros de estética facial y gradiente sociogenético en niños chilenos

PURPOSE: to compare anthropometric measurements of facial esthetics in 5 and 8 years old children, with normal physical and occlusal characteristics, belonging to different sociogenetic groups from Santiago de Chile (mixed ethnic population); and with north American Caucasian parameters published by Farkas. METHODS: a facial analysis based on Arnett and Farkas was carried out, using digital photography supported by a clinical examination, in four samples, according to the dentition and sociogenetic stratum. RESULTS: the results show no differences in Chile according to sex and stratum, neither with Caucasian measurements. CONCLUSION: the anthropometric measurements of facial aesthetics in sociogenetic groups from Santiago are not different with Farkas Caucasian measurements and can be used for clinical purposes in mixed ethnically Chilean populations.

Articulación de fones en individuos clase esqueletal I,II y III

PURPOSE: to determine the consonant phonemes articulation patterns in Chilean skeletal class I, II and III Spanish speakers and compare their phonetic differences. METHODS: fifty-four skeletal class I, II and III subjects were selected, based on intraoral clinical examination and Ricketts cephalometric analysis, constituting the study groups. A standardized phonoarticulatory test was applied to each patient to determine the modified phonemes and their compensatory patterns. RESULTS: the findings indicate changes in articulation in all three groups. Significant differences were found in anterior and medium phonemes between skeletal class I and II and only in the anterior phonemes between skeletal class I and III. There were no significant differences between II and III skeletal groups. Qualitatively different modifications and compensations between skeletal classes are reported. CONCLUSION: different degree of modification in consonant phonemes articulation is shown in class II and III patients when compared to class I skeletal subjects. These differences are related to the skeletal patterns.

Family aggregation of language impairment in an isolated Chilean population from Robinson Crusoe Island: LI aggregation in an isolated Chilean population

BACKGROUND It has been reported that the inhabitants of the Chilean Robinson Crusoe Island have an increased frequency of specific language impairment (SLI) or developmental language disorder (DLD). AIMS To explore the familial aggregation of DLD in this community. METHODS & PROCEDURES We assessed the frequency of DLD amongst colonial children between the ages of 3 and 8;11 years (50 individuals from 45 nuclear families). Familial aggregation rates of language disorder were calculated by assessing all available first-degree relatives (n = 107, 77 parents, 25 siblings, five half-siblings) of the probands. OUTCOMES & RESULTS We found that 71% of the child population performed significantly below expected in measures of phonological production or expressive and receptive morphology. The majority of these children presented with severe expressive and/or receptive language difficulties. One-quarter of language-disordered probands primarily had phonological difficulties. Family members of affected probands experienced a higher risk of language disorder than those of typically developing probands. This increased risk was apparent regardless of non-verbal IQ. CONCLUSIONS & IMPLICATIONS The study substantiates the existence of a familial form of speech and language disorder on Robinson Crusoe Island. Furthermore, we find that the familiarity is stable regardless of non-verbal IQ, supporting the recent movement to reduce the importance of non-verbal IQ criterion in DLD diagnoses.

Correction: Exome Sequencing in an Admixed Isolated Population IndicatesNFXL1 Variants Confer a Risk for Specific Language Impairment (PLoS Genet, 11(6), (2015))

Pía Villanueva, Ron Nudel, Alexander Hoischen, María Angélica Fernández, Nuala H. Simpson, Christian Gilissen, Rose H. Reader, Lillian Jara, María Magdalena Echeverry, Clyde Francks, Gillian Baird, Gina Conti-Ramsden, Anne O’Hare, Patrick F. Bolton, Elizabeth R. Hennessy, SLI Consortium, Hernán Palomino, Luis Carvajal-Carmona, Joris A. Veltman, Jean-Baptiste Cazier, Zulema De Barbieri, Simon E. Fisher, Dianne F. Newbury

PIAHO: una herramienta para la prevención de hábitos orales deletéreos (protocolo de incorporación apropiada de hábitos orales)

Purpose to present a tool to prevent bad oral habits ocurrance, this protocol is called PIAHO. Methods comparing the diagnoses obtained by PeNaF subjective test with nasal resistance diagnoses obtained by the objective test of rhinomanometry. It was explored the relationships between the incorporation of consistencies, tools and choice of positions during feeding and swallowing different types. Based on both, the results obtained and published research in Chilean population; as in the international literature review. Results a new strategy and guidelines for a early inclusion of consistencies and feeding tools, also focus in a good nasal hygiene. Conclusion to contribute to the prevention of orofacial myofunctional disorders and avoiding oral bad habits occurrence.