Angelman Syndrome due to familial translocation: unexpected additional results characterized by Microarray-based Comparative Genomic Hybridization.

BACKGROUND: The 15q11q13 region is subject to imprinting and is involved in various structural rearrangements. Less than 1% of Angelman Syndrome patients are due to translocations involving 15q11q13. These translocations can arise de novo or result from the segregation of chromosomes involved in a familial balanced translocation. RESULTS: A 5-year-old Mexican girl presented with developmental delay, minor dysmorphic features and history of exotropia. G-banding chromosome analysis established the diagnosis of Angelman Syndrome resulting from a familial translocation t(10;15) involving the 15q11.2 region. The available family members were studied using banding and molecular cytogenetic techniques, including Microarray-based Comparative Genomic Hybridization, which revealed additional unexpected results: a coincidental and smaller 15q deletion, asymptomatic duplications in 15q11.2 and Xp22.31 regions. CONCLUSIONS: This report demonstrates the usefulness of array CGH for a detailed characterization of familial translocations, including the detection of submicroscopic copy number variations, which would otherwise be missed by karyotype analysis alone. Our report also expands two molecularly characterized rare patient cohorts: Angelman Syndrome patients due to familial translocations and patients with 15q11.2 duplications of paternal origin.

Cytogenomic and phenotypic analysis in low-level monosomy 7 mosaicism with non-supernumerary ring chromosome 7.

We present the literature review of ring chromosome 7 and clinical, cytogenetic and fine molecular mapping of the first postnatal report of a male child with a non-supernumerary ring chromosome 7, r(7). The patient had dysmorphic features, developmental delay, dermatologic lesions with variable pigmentation, hypogenitalism, lumbar dextroscoliosis, cerebellar and ophthalmological abnormalities, and melanocytic congenital nevi. Cytogenetic analysis of peripheral blood and the nevus sample showed the presence of three different cell lines r(7), monosomy 7, and duplicated r(7) (idic r(7)), while findings on fibroblasts from both light and dark skin showed only mosaicism with r(7) and monosomy 7 cell lines in various proportions. FISH assay of the ring chromosome showed subtelomeric loss in both chromosome arms in all tissues studied. Analysis by genome-wide single-nucleotide polymorphism array showed a 0.8 Mb deletion in 7p22.3 (involving eight genes) and a 7.5 Mb deletion in 7q36 (involving 29 genes including some involved in genital and central nervous system development). The combination of results from our karyotypic and array analyses enabled us to establish an accurate genotype-phenotype relationship.

[Prenatal molecular diagnosis of a DMD carrier female fetus by chorionic villus sampling and linkage analysis]. / Diagnóstico prenatal molecular en un feto portador del alelo para distrofia muscular de Duchenne mediante biopsia de vellosidades coriónicas. Reporte de un caso y revisión bibliográfica.

BACKGROUND: Duchenne muscular dystrophy (DMD) is the most frequent inherited and lethal neuromuscular disorder in humans. Molecular prenatal diagnosis of DMD through amniocentesis is a real preventive reproductive option in our country, although experience with chorionic villus sampling is still limited (CVS). OBJECTIVE: Perform the first prenatal diagnosis in an obligate DMD carrier woman in Mexico by CVS. MATERIAL AND METHOD: CVS was performed in an obligate DMD carrier woman in which no partial intragenic deletions were present but a haplotype at-risk was identified. Cytogenetic analysis with GTG banding was performed and genomic DNA extraction from CVS sample was done without culture. Fetal gender assignment was achieved by ultrasonography at 12 weeks of gestation and confirmed by PCR amplification of two Y chromosome-linked loci (SRY and DYS389I/II). Identification of the DMD haplotype at-risk in the fetus was done through analysis of the intragenic markers pERT87.8/TaqI and pERT87.15/Xmnl. RESULTS: Absence of PCR products corresponding to Y chromosome-linked loci in DNA CVS sample was compatible with a female fetus; it was confirmed later by cytogenetic study and prenatal ultrasound follow-up. Linkage analysis reveals that the female fetus inherited the DMD haplotype at-risk. We did not identify any maternal DNA contamination in CVS molecular analysis and these results were postnatally confirmed in DNA obtained from buccal cells. CONCLUSION: Molecular prenatal diagnosis through chorionic villus sampling could be an early reproductive prevention strategy applicable to Duchenne/Becker muscular dystrophy carrier women in our country.

Cardiovascular spectrum in Williams-Beuren syndrome: the Mexican experience in 40 patients.

In this study, we have identified and evaluated the cardiovascular anomalies associated with Williams-Beuren syndrome in children.In a retrospective, lineal, and observational study, we reviewed the files of children who were seen from 1980 through 2005 (25 years) after a clinical diagnosis of Williams-Beuren syndrome.Forty children were diagnosed with this syndrome at the National Institute of Pediatrics in Mexico City. Of these, 32 (80%) were found to have congenital heart defects. The male-to-female ratio was 1.3:1 and ages ranged from 6 months to 15 years (mean, 4.4 years) at the time of diagnosis. All of the patients had morphologic and genetic characteristics typical of the syndrome.We emphasize the cardiovascular aspects from a clinical point of view. Supravalvular aortic stenosis was our most frequent finding, in 18 of 32 patients (56%); gradient differences in these patients ranged from 14 to 81 mmHg. Five patients showed combined lesions, the most frequent being supravalvular aortic stenosis in combination with pulmonary artery brachial stenosis, or with atrial and ventricular defects. Patients with incomplete atrioventricular defect and bicuspid aortic valve, as were seen at our hospital, have not to our knowledge been reported in other studies.One of the patients was scheduled for balloon dilation; another was scheduled for surgery; a 3rd patient was operated on twice for the placement of an aorto-aortic bridge; another underwent ventricular septal defect closure; and yet another underwent aortoplasty, this last dying shortly after surgery.

Growth, growth velocity and adult height in Mexican girls with Turner's syndrome.

This was a prospective, longitudinal and descriptive study of 117 Mexican girls with Turner's syndrome (TS) followed from diagnosis to 18 years old. Height, weight and growth velocity were evaluated every 4-6 months, and bone age was assessed annually. Adult height was reached in 87 girls. All the girls were treated during 1 year with conjugated estrogens at bone age of 12 years, and subsequently with mixed estrogen/progestogen. Growth retardation in girls with TS is apparent at birth (2.7 +/- 0.9 kg and 46.3 +/- 5.0 cm) and in childhood, but becomes most marked when puberty would normally occur. Mean growth velocity was less than 25th percentile from birth to 2 years, less than 10th percentile between 3-9 years, and less than 3rd percentile from 10 to 18 years of age. Final adult height was 136.9 +/- 5.5 cm, but it is affected by the particular karyotype: 46,Xi(Xq): 134.5 cm, 45,XO: 137.3 cm, and 45XO/46,XX: 139 cm.