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Objectives: To report the benefits of genetic diagnosis in patients with retinoblastoma., Method: Observational study. Patients with retinoblastoma and their families were included. Demographic and clinical data were recorded. Blood and tumour samples were obtained. Next generation sequencing was performed on the samples. When deletion 13 q syndrome was suspected, cytogenetics microarray was performed (Cytoscan® HD, Affymetrix, Santa Clara, CA, USA), with a high density chip of 1.9 million of non-polymorphic probes and 750 thousand SNP probes., Results: Of the 7 cases were analysed 4 were male. The mean age at diagnosis was 21 months (range 5-36). Three cases had bilateral retinoblastoma, and 4 unilateral. None had family history. In all patients, blood was analysed, and a study was performed on the tissue from 2 unilateral enucleated tumours, in which 6 mutations were identified, all de novo. Just one was novel (c.164delC; case 1). One case of unilateral tumour revealed blood mosaicism, showing that his condition was inheritable, and that there is a high risk of developing retinoblastoma in the unaffected eye. The patient also has an increased risk of presenting with other primary tumours., Conclusion: Molecular diagnosis of RB1 in patients with retinoblastoma impacts on the decision process, costs, treatment, and prognosis of patients, as well as their families., (Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Genomic imprinting is a reversible phenomenon that affects the expression of genes depending on their parental origin. The best characterized human disorders resulting from an alteration of the imprinting process are Angelman and Prader-Willi syndromes. They are due to the lack of active maternal or paternal genes, respectively, from chromosome region 15q11q13. Most cases arise via interstitial deletions. We review evidence that other common cytogenetic alterations of this region, interstitial and supernumerary duplications, could be the reciprocal products of the deletions and are also affected by the imprinting phenomenon, given the predominance of maternally-derived duplications in patients ascertained due to developmental delays or autistic features.

Methylmalonic acidemia is an inborn error of metabolism known to be a cause of ketoacidosis and mental retardation. The less severe mut(-) form of the disorder, however, has been described with only mild to moderate cognitive deficits or, rarely, with normal neurodevelopment in asymptomatic cases. Nevertheless, there has been no detailed documentation of long-term neuropsychological function in the mut(-) form and relatively few IQ scores. We performed longitudinal developmental and neuropsychological assessments on a girl with symptomatic mut(-) methylmalonic acidemia whose biochemical abnormalities were in the moderately severe range and who had had recurrent episodes of ketoacidosis. At almost 12 years of age, her full scale IQ on the Wechsler Intelligence Scale, third edition, was 129 with very superior and superior scores on nonverbal and verbal skills, respectively. On the National Achievement Test she scored above the 99th percentile in the Basic Battery and is considered to be a gifted student. This outcome suggests that the spectrum of cognitive attainment in mut(-) methylmalonic acidemia is wide and that even a moderate degree of biochemical severity with ketoacidotic episodes may not result in cognitive deficit. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:192-195, 2000., (Copyright 2000 Wiley-Liss, Inc.)

Duplications of chromosome region 15q11q13 often occur as a supernumerary chromosome 15. Less frequently they occur as interstitial duplications [dup(15)]. We describe the clinical and molecular characteristics of three patients with de novo dup(15). The patients, two males and one female (ages 3-21 years), had nonspecific findings that included autistic behavior, hypotonia, and variable degrees of mental retardation. The extent, orientation, and parental origin of the duplications were assessed by fluorescent in situ hybridization, microsatellite analyses, and methylation status at D15S63. Two patients had large direct duplications of 15q11q13 [dir dup(15)(q11q13)] that extended through the entire Angelman syndrome/Prader-Willi syndrome (AS/PWS) chromosomal region. Their proximal and distal breaks, at D15S541 or D15S9 and between D15S12 and D15S24, respectively, were comparable to those found in the common AS/PWS deletions. This suggests that duplications and deletions may be the reciprocal product of an unequal recombination event. These two duplications were maternally derived, but the origin of the chromatids involved in the unequal crossing over in meiosis differs. In one patient, the duplication originated from two different maternal chromosomes, while in the other patient it arose from the same maternal chromosome. The third patient had a much smaller duplication that involved only D15S11 and parental origin could not be determined. There was no obvious correlation between phenotype and extent of the duplication in these patients.

We describe a newborn male with minor facial anomalies, pyloric stenosis, and a chromosome rearrangement that involves deletion and addition of material at 9p24.3. Routine studies showed a 46, XY, add (9) (p24) karyotype. Fluorescence in situ hybridization (FISH) with two different whole chromosome probes for chromosome 9 failed to identify whether the additional material was derived from that chromosome. FISH with single copy YAC probes from 9p24 (D9S1858, D9S1813 and D9S54) showed a more complex rearrangement involving a deletion at D9S1858 but not at D9S1813 or D9S54. Parental chromosome studies demonstrated an apparently identical 9p abnormality in the patient's mother. This report describes a familial chromosome rearrangement in an abnormal child and his normal mother and demonstrates the use and limitations of FISH in characterizing chromosomal abnormalities.