Saliva DNA: An alternative biospecimen for single nucleotide polymorphism chromosomal microarray analysis in autism.

Chromosomal microarray analysis (CMA) is typically performed for investigation of autism using blood DNA. However, blood collection poses significant challenges for autistic children with repetitive behaviors and sensory and communication issues, often necessitating physical restraint or sedation. Noninvasive saliva collection offers an alternative, however, no published studies to date have evaluated saliva DNA for CMA in autism.

SNP chromosome microarray genotyping for detection of uniparental disomy in the clinical diagnostic laboratory.

Single nucleotide polymorphism (SNP) chromosome microarray is well established for investigation of children with intellectual deficit/development delay and prenatal diagnosis of fetal malformation but has also emerged for uniparental disomy (UPD) genotyping. Despite published guidelines on clinical indications for testing there are no laboratory guidelines published for performing SNP microarray UPD genotyping. We evaluated SNP microarray UPD genotyping using Illumina beadchips on family trios/duos within a clinical cohort (n=98) and then explored our findings in a post-study audit (n=123).

Whole Genome Sequencing, Focused Assays and Functional Studies Increasing Understanding in Cryptic Inherited Retinal Dystrophies.

The inherited retinal dystrophies (IRDs) are a clinically and genetically complex group of disorders primarily affecting the rod and cone photoreceptors or other retinal neuronal layers, with emerging therapies heralding the need for accurate molecular diagnosis. Targeted capture and panel-based strategies examining the partial or full exome deliver molecular diagnoses in many IRD families tested. However, approximately one in three families remain unsolved and unable to obtain personalised recurrence risk or access to new clinical trials or therapy.

FISH analysis of brain smears obtained at intraoperative diagnosis - An accurate and fast method to detect 1p/19q-codeletion in gliomas.

The importance of molecular testing of gliomas is highlighted in the 2016 revised 4th edition of the WHO Classification of Tumours of the Central Nervous System, which applies an integrated diagnosis of histological and molecular features. In this classification system, oligodendrogliomas (ODG) are defined as IDH-mutant and 1p/19q-codeleted. Fluorescence in situ hybridization (FISH) analysis of formalin-fixed paraffin-embedded (FFPE) tissue is a standard method of determining 1p/19q-codeletion.

A Paediatric Acute Promyelocytic Leukaemia Patient Harbouring a Cryptic PML-RARA Insertion due to a Complex Structural Chromosome 17 Rearrangement.

Acute promyelocytic leukaemia with PML-RARA fusion is usually associated with the t(15;17)(q24.1;q21.1) translocation but may also arise from complex or cryptic rearrangements.

Chromosomal rearrangements and novel genes in disorders of eye development, cataract and glaucoma.

Disorders of eye development such as microphthalmia and anophthalmia (small and absent eyes respectively), anterior segment dysgenesis where there may be pupillary and iris anomalies, and associated cataract and glaucoma, often lead to visual impairment or blindness. Currently treatment options are limited, as much is unknown about the molecular pathways that control normal eye development and induce the aberrant processes that lead to ocular defects. Mutation detection rates in most of the known genes are generally low, emphasizing the genetic heterogeneity of developmental ocular defects.

Two mosaic terminal inverted duplications arising post-zygotically: Evidence for possible formation of neo-telomeres.

Objective: To elucidate the structure of terminal inverted duplications and to investigate potential mechanisms of formation in two cases where there was mosaicism with cells of apparently normal karyotype.

Results: A karyotype [46,XY,inv dup(4)(p16.3p15.

Paternally inherited submicroscopic duplication at 11p15.5 implicates insulin-like growth factor II in overgrowth and Wilms' tumorigenesis.

Loss of imprinting at insulin-like growth factor II (IGFII), in association with H19 silencing, has been described previously in a subgroup of Beckwith-Wiedemann syndrome (BWS) patients who have an elevated risk for Wilms' tumor. An equivalent somatic mutation occurs in sporadic Wilms' tumor. We describe a family with overgrowth in three generations and Wilms' tumor in two generations, with paternal inheritance of a cis-duplication at 11p15.

Deletion at 14q22-23 indicates a contiguous gene syndrome comprising anophthalmia, pituitary hypoplasia, and ear anomalies.

Anophthalmia and pituitary gland hypoplasia are both debilitating conditions where the underlying genetic defect is unknown in the majority of cases. We identified a patient with bilateral anophthalmia and absence of the optic nerves, chiasm and tracts, as well as pituitary gland hypoplasia and ear anomalies with a de novo apparently balanced chromosomal translocation, 46,XY,t(3;14)(q28;q23.2).

Tumor protein D52 (TPD52) is overexpressed and a gene amplification target in ovarian cancer.

Recurrent chromosome 8q gain in ovarian carcinoma is likely to reflect the existence of multiple target loci, as the separate gain of chromosome bands 8q21 and 8q24 has been reported in independent studies. Since tumor protein D52 (TPD52) has been identified as a chromosome 8q21 amplification target in breast and prostate carcinoma, we compared TPD52 expression in normal ovarian epithelium (n = 9), benign serous adenomas (n = 11), serous borderline tumors (n = 6) and invasive carcinomas of the major histologic subtypes (n = 57) using immunohistochemistry. These analyses revealed that all normal ovarian epithelium samples and benign serous tumors were predominantly TPD52-negative, whereas TPD52 was overexpressed in most (44/57; 77%) ovarian carcinomas regardless of histologic subtype.

Axenfeld-Rieger malformation and distinctive facial features: Clues to a recognizable 6p25 microdeletion syndrome.

Deletion of distal 6p is associated with a distinctive clinical phenotype including Axenfeld-Rieger malformation, hearing loss, congenital heart disease, dental anomalies, developmental delay, and a characteristic facial appearance. We report the case of a child where recognition of the specific ocular and facial phenotype, led to identification of a 6p microdeletion arising from a de novo 6:18 translocation. Detailed analysis confirmed deletion of the FOXC1 forkhead gene cluster at 6p25.

Three patients with terminal deletions within the subtelomeric region of chromosome 9q.

We report on three male infants with de novo terminal deletions of chromosome 9q34.3. The clinical features are compared to the nine cases described in the literature.

Chromosome loops arising from intrachromosomal tethering of telomeres occur at high frequency in G1 (non-cycling) mitotic cells: Implications for telomere capture.

BACKGROUND: To investigate potential mechanisms for telomere capture the spatial arrangement of telomeres and chromosomes was examined in G1 (non-cycling) mitotic cells with diploid or triploid genomes. This was examined firstly by directly labelling the respective short arm (p) and long arm subtelomeres (q) with different fluorophores and probing cell preparations using a number of subtelomere probe pairs, those for chromosomes 1, 3, 4, 5, 6, 7, 9, 10, 12, 17, 18, and 20. In addition some interstitial probes (CEN15, PML and SNRPN on chromosome 15) and whole chromosome paint probes (e.

Use of two FISH probes provides a cost-effective, simple protocol to exclude an imprinting centre defect in routine laboratory testing for suspected Prader-Willi and Angelman syndrome.

From among the many suspected patients with Prader-Willi (PWS) or Angelman (AS) syndromes received for diagnosis in a routine genetics laboratory, we present our protocol for the exclusion of a possible, rare imprinting centre (IC) defect. Deletion detection utilising two FISH probes-SNRPN within the IC, and another probe outside the IC, on the same suspension remaining from the cytogenetic harvest, provides a simple, quick and cost-effective system for exclusion of an IC defect, for patients with an abnormal methylation analysis.

Apparently unrelated cytogenetic abnormalities among 462 probands referred for the detection of del(22q) by FISH.

Laboratory-based reports of the cytogenetic abnormalities detected during the course of testing for deletion del(22q) are scant. We report our findings from the testing with FISH of 462 patients suspected to have del(22q) between 1994 and 2000. Of these, 447 had a normal karyotype.