Genetic Screening of the Usher Syndrome in Cuba.

BACKGROUND: Usher syndrome (USH) is a recessive inherited disease characterized by sensorineural hearing loss, retinitis pigmentosa, and sometimes, vestibular dysfunction. Although the molecular epidemiology of Usher syndrome has been well studied in Europe and United States, there is a lack of studies in other regions like Africa or Central and South America. METHODS: We designed a NGS panel that included the 10 USH causative genes (MYO7A, USH1C, CDH23, PCDH15, USH1G, CIB2, USH2A, ADGRV1, WHRN, and CLRN1), four USH associated genes (HARS, PDZD7, CEP250, and C2orf71), and the region comprising the deep-intronic c.7595-2144A>G mutation in USH2A. RESULTS: NGS sequencing was performed in 11 USH patients from Cuba. All the cases were solved. We found the responsible mutations in the USH2A, ADGRV1, CDH23, PCDH15, and CLRN1 genes. Four mutations have not been previously reported. Two mutations are recurrent in this study: c.619C>T (p.Arg207∗) in CLRN1, previously reported in two unrelated Spanish families of Basque origin, and c.4488G>C (p.Gln1496His) in CDH23, first described in a large Cuban family. Additionally, c.4488G>C has been reported two more times in the literature in two unrelated families of Spanish origin. CONCLUSION: Although the sample size is very small, it is tempting to speculate that the gene frequencies in Cuba are distinct from other populations mainly due to an "island effect" and genetic drift. The two recurrent mutations appear to be of Spanish origin. Further studies with a larger cohort are needed to elucidate the real genetic landscape of Usher syndrome in the Cuban population.

Unusual de novo Partial Trisomy 17p12p11.2 due to Unbalanced Insertion into 5p13.1 in a Severely Affected Boy.

Gain of copy numbers can be due to different chromosomal rearrangements such as direct or indirect duplications, translocations, small supernumerary marker chromosomes, or insertions. In a 3-year-old boy with dysmorphic features and developmental delay, chromosome analyses revealed a derivative chromosome 5. Microdissection and reverse fluorescence in situ hybridization identified the in 5p13.1 inserted part as 17p12-p11.2 material. Thus the patient suffered from a rare combination of genomic disorder, that is, Charcot-Marie-Tooth disease type 1A and Potocki-Lupski syndrome. Parental studies indicated that the abnormality was de novo in origin. As the question how this rearrangement arose cannot be answered conclusively, formal genetic counseling is warranted, which includes a discussion regarding the possibility of gonadal mosaicism. In conclusion, this case highlights that chromosome 17p is genetically relatively instable, and thus it can lead to rare chromosomal conditions.

Epidemiology of prenatal genetic and environmental factors of mental retardation in cuba.

Introduction: One of the most sensitive disabilities in human beings is intellectual disability. In April, 2003, a 10-month study was completed of all persons in Cuba with mental retardation (MR), producing results that included epidemiological variables on a national scale. Objective: Through follow-up research, this paper describes and analyzes 4 prenatal factors associated with MR: Down syndrome (DS), fragile X syndrome (FXS), consanguinity, and maternal alcohol use during pregnancy, in order to provide recommendations for health system decision-makers on consolidating prevention strategies at the community level and improving individual attention to persons with MR. Materials & Methods: All studies were carried out on the basis of strict ethical principles. Data for the 4 prenatal factors was gleaned from the national study's database. Additional data on affected individuals was obtained through home visits. A previously developed screening instrument was used for clinical genetic analysis to classify possible MR causal factors as prenatal, perinatal, postnatal, psychosis, and unclassifiable. Prenatal included causal factors such as: genetic (by clinical genetic examination, metabolic screening in urine, and routine karyotypes); nonspecific (evidence of prenatal causal factor without diagnosis of genetic or environmental etiology); and environmental (prenatal medical history of biological, physical, or chemical teratogens, endocrine-metabolic diseases, or other maternal diseases known to affect fetal neurodevelopment). Frequency, prevalence, and percentages were reported using a descriptive statistical method. Impact of interventions and actions over time were also compared. Results: MR prevalence in Cuba is 1.25%, lower than the value of 2%-3% reported in developed countries. National prevalence of DS was found to be 4.3 per 10,000 population, representing 22.1% of persons with MR attributed to an ascertained genetic cause. FXS prevalence in a population of individuals of both sexes with MR, initially classified as nonspecific prenatal, psychosis, and unclassifiable, was 2.5 per 1,000 of that population; however, in males of the same population, prevalence was 3.7 per 1,000. At this first stage, such results indicate that this syndrome contributes biologically to the 1.46:1 male/female ratio among the 140,489 individuals with MR. Maternal alcohol use during pregnancy was found in 4.22% of persons with MR and consanguinity was present in 6.89% of the population with MR (10.9% of persons with mild prenatal MR and 14.2% with severe MR). This national data is subdivided by regions and provinces in this paper. Conclusions: Prevalence of MR in Cuba is lower than reference values for developed countries. Knowledge generated by this study about 4 specific causes of MR constitutes pioneering research in the Cuban context, contributing to the field of medical genetics. The results offer the basis for formulation of new scientific contributions related to MR genetics as well as preventive approaches to such genetic factors as consanguinity and to environmental factors such as maternal alcohol use during pregnancy, which affect or target embryo-fetal development of the nervous system.