Poland-Möbius syndrome: a case report implicating a novel mutation of the PLXND1 gene and literature review.

Background: Möbius (Moebius) and Poland's syndromes are two rare congenital syndromes characterized by non-progressive bilateral (and often asymmetric) dysfunction of the 6 and 7 cranial nerves and hypoplasia of the pectoral muscles associated with chest wall and upper limb anomalies respectively. Manifest simultaneously as Poland-Möbius (Poland-Moebius) syndrome, debate continues as to whether this is a distinct nosological entity or represents phenotypic variation as part of a spectrum of disorders of rhomboencephalic development. Etiological hypotheses implicate both genetic and environmental factors.

Observations on the Natural History of Camurati-Engelmann Disease.

Camurati-Engelmann disease (OMIM 31300) is a rare cranio-tubular bone dysplasia characterized by osteosclerosis of the long bones and skull caused by dominantly-inherited mutations in the transforming growth factor beta 1 (TGFB1) gene. A wide variation in phenotype has been recognized, even within families carrying the same mutation. In addition, aspects of the natural history of the disorder, in particular whether it is always progressive or can remit spontaneously, remain uncertain.

Massively Parallel Sequencing of Genes Implicated in Heritable Cardiac Disorders: A Strategy for a Small Diagnostic Laboratory.

Sudden cardiac death (SCD) in people before the age of 35 years is a devastating event for any family. The causes of SCD in the young can be broadly divided into two groups: heritable cardiac disorders that affect the heart structure (cardiomyopathies) and primary electrical disorders (cardiac ion channelopathies). Genetic testing is vital as those suffering from cardiac ion channelopathies have structurally normal hearts, and those with cardiomyopathies may only show subtle abnormalities in the heart and these signs may not be detected during an autopsy.

Splice Site Variants in the and Genes: Transcript Analysis as a Tool in Supporting Pathogenicity.

Background: Approximately 75% of clinically definite long QT syndrome (LQTS) cases are caused by mutations in the , and genes. Of these mutations, a small proportion (3.2-9.

Two Novel GLDC Mutations in a Neonate with Nonketotic Hyperglycinemia.

Nonketotic hyperglycinemia, also known as glycine encephalopathy (OMIM #605899), is an autosomal recessive disorder of glycine metabolism resulting from a defect in the glycine cleavage system. We report two novel mutations of the glycine decarboxylase (GLDC) gene observed in a compound heterozygous state in a neonate of mixed Maori and Caucasian parentage: c.395C>T p.

Evaluation of Bioinformatic Programmes for the Analysis of Variants within Splice Site Consensus Regions.

The increasing diagnostic use of gene sequencing has led to an expanding dataset of novel variants that lie within consensus splice junctions. The challenge for diagnostic laboratories is the evaluation of these variants in order to determine if they affect splicing or are merely benign. A common evaluation strategy is to use in silico analysis, and it is here that a number of programmes are available online; however, currently, there are no consensus guidelines on the selection of programmes or protocols to interpret the prediction results.

Brain dopamine-serotonin vesicular transport disease presenting as a severe infantile hypotonic parkinsonian disorder.

Two male siblings from a consanguineous union presented in early infancy with marked truncal hypotonia, a general paucity of movement, extrapyramidal signs and cognitive delay. By mid-childhood they had made little developmental progress and remained severely hypotonic and bradykinetic. They developed epilepsy and had problems with autonomic dysfunction and oculogyric crises.

Array comparative genomic hybridization identifies a heterozygous deletion of exon 3 of the RYR2 gene.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a heritable cardiac disorder characterized by life-threatening ventricular tachycardia caused by exercise or acute emotional stress. The standard diagnostic screening involves Sanger-based sequencing of 45 of the 105 translated exons of the RYR2 gene, and copy number changes of a limited number of exons that are detected using multiplex ligation-dependent probe amplification (MLPA).

Methods: In the current study, a previously validated bespoke array comparative genomic hybridization (aCGH) technique was used to detect copy number changes in the RYR2 gene in a 43-year-old woman clinically diagnosed with CPVT.

Diagnostic Screening Workflow for Mutations in the BRCA1 and BRCA2 Genes.

Objectives: Screening for mutations in large genes is challenging in a molecular diagnostic environment. Sanger-based DNA sequencing methods are largely used; however, massively parallel sequencing (MPS) can accommodate increasing test demands and financial constraints. This study aimed to establish a simple workflow to amplify and screen all coding regions of the BRCA1 and BRCA2 (BRCA1/2) genes by Sanger-based sequencing as well as to assess a MPS approach encompassing multiplex polymerase chain reaction (PCR) and pyrosequencing.

SNP Analysis and Whole Exome Sequencing: Their Application in the Analysis of a Consanguineous Pedigree Segregating Ataxia.

Autosomal recessive cerebellar ataxia encompasses a large and heterogeneous group of neurodegenerative disorders. We employed single nucleotide polymorphism (SNP) analysis and whole exome sequencing to investigate a consanguineous Maori pedigree segregating ataxia. We identified a novel mutation in exon 10 of the SACS gene: c.

Array comparative genomic hybridization identifies a heterozygous deletion of the entire KCNJ2 gene as a cause of sudden cardiac death.

Background: Large gene rearrangements, not detectable by standard molecular genetic sequencing techniques, are present in a minority of patients with long QT syndrome. We aimed to screen for large rearrangements in genes responsible for long QT syndrome as part of the molecular autopsy of a 36-year-old woman who died suddenly and had a negative autopsy. A retrospective analysis of an ECG identified a long QT interval, but sequencing of known LQT genes was uninformative.

Diagnostic genetics at a distance: von hippel-lindau disease and a novel mutation.

Genetic testing at a distance is commonplace where members of a family with a segregating germline mutation are geographically separated. For the most part, this challenge is addressed through the intervention of health professionals in taking and/or processing blood samples for subsequent couriering of DNA to a referral laboratory. In some circumstances, however, the collecting of pivotal clinical material may involve direct patient involvement.