147 research outputs found
A Novel MECP2 Mutation in a Boy with Neonatal Encephalopathy and Facial Dysmorphism
No full textMethly-CpG-binding protein 2 (MECP2) mutations cause Rett syndrome in females. Here we report on a male infant with neonatal encephalopathy, myoclonic jerks, and irregular breathing patterns caused by a novel frameshift mutation in the MECP2 gene. In addition he has facial dysmorphisms previously not described in these patients. (J Pediatr 2009; 155:140-3
Familial intellectual disability and autistic behavior caused by a small FMR2 gene deletion
No full textAlterations of the Fragile Mental Retardation 2 gene (FMR2, synonym AFF2) can result in non-specific, mild to borderline X-linked intellectual disability (XLID), and behavioral problems. The well-known molecular pathomechanism of this condition, also referred to as FRAXE, is a (CCG)(n) trinucleotide repeat expansion which leads to silencing of the FMR2 gene. However, deletions within the FMR2 gene may also be causative of the disorder. Here, we report on two brothers diagnosed with FRAXE in whom a small deletion in the FMR2 gene was detected by whole genome array comparative genomic hybridization (CGH). The deletion was also present in their clinically healthy mother and maternal uncle who was similarly affected, but not in a healthy older brother of the two patients. Our observation demonstrates that FMR2 gene deletions may contribute to the FRAXE phenotype. Therefore, we suggest that screening for FMR2 gene deletions using array CGH should be considered in patients with non-specific XLID and absent trinucleotide expansion. (C) 2011 Wiley-Liss, Inc
Overlap of Moebius and oromandibular limb hypogenesis syndrome with gastroschisis and pulmonary hypoplasia
No full textThe oromandibular limb hypogenesis syndromes (OLHS) represent a group of rare conditions characterized by congenital malformations involving the tongue, mandible, and limbs. There is considerable overlap between the syndromes gathered under the term OLHS, and a marked variability of face and limb anomalies as well as additional malformations. In this report we describe a girl with gastroschisis and pulmonary hypoplasia in addition to features of Moebius syndrome comprising hypoplasia of the tongue and mandible, brachydactyly of halluces, cranial nerve palsies with bilateral facial paralysis and an inability to execute horizontal eye movements. Karyotyping and array-based comparative genomic hybridization were normal. This observation confirms an overlap between Moebius syndrome and OLHS and widens the spectrum of associated malformations. Intrauterine environmental factors including vascular insufficiency, high maternal fever, and drug abuse are likely to play a crucial role in the pathogenesis of this condition. (C) 2009 Wiley-Liss, Inc
Code Flows: Visualizing Structural Evolution of Source Code
No full textUnderstanding detailed changes done to source code is of great importance in software maintenance. We present Code Flows, a method to visualize the evolution of source code geared to the understanding of fine and mid-level scale changes across several file versions. We enhance an existing visual metaphor to depict software structure changes with techniques that emphasize both following unchanged code as well as detecting and highlighting important events such as code drift, splits, merges, insertions and deletions. The method is illustrated with the analysis of a real-world C++ code system.
A disease causing deletion of 29 base pairs in intron 15 in the MKS1 gene is highly associated with the campomelic variant of the Meckel-Gruber syndrome
No full textMeckel-Gruber syndrome (MKS) is an autosomal recessive disorder causing severe defects in the developing central nervous system and other organs. Recently, mutations in the MKS1 gene have been identified as disease causing in individuals of Finnish MKS families. The primary aim of the present study was to assess the frequency of the 'Finnish founder mutation' (29 bp IVS15-7_35) in the MKS1 gene in 20 aborted fetuses with a diagnosis of MKS. The secondary aim was to screen for novel mutations in the coding sequence of the MKS1 gene of MKS fetuses and to obtain genotype-phenotype correlations where possible. Furthermore, we evaluated the carrier rate of a deletion of 29 bp in intron 15 of the MKS1 gene in a German population. To identify and characterize mutations in the MKS1 gene, sequence analyses and quantitative real time polymerase chain reaction studies were performed. We could identify the same type of mutation, a deletion of 29 bp in intron 15 of the MKS1 gene, in 8 out of the 20 cases studied. Six out of the eight cases with such a mutation displayed the campomelic variant of MKS. The carrier frequency among 519 healthy German individuals was 1:260. This deletion in the MKS1 gene is highly associated with a distinct subtype of the MKS, namely the campomelic variant. In individuals of European origin suffering from the campomelic MKS variant, the described deletion is highly likely to be causative. Regarding the results of our study, the incidence of MKS in Germany can be estimated as 1:135,000. In families with a known mutation in the MKS1 gene, it is now possible to offer an early prenatal testing, for example with chorionic villus sampling and mutation analysis
Identification of subtelomeric genomic imbalances and breakpoint mapping with quantitative PCR in 296 individuals with congenital defects and/or mental retardation
No full textAbstract Background Submicroscopic imbalances in the subtelomeric regions of the chromosomes are considered to play an important role in the aetiology of mental retardation (MR). The aim of the study was to evaluate a quantitative PCR (qPCR) protocol established by Boehm et al. (2004) in the clinical routine of subtelomeric testing. Results 296 patients with MR and a normal karyotype (500–550 bands) were screened for subtelomeric imbalances by using qPCR combined with SYBR green detection. In total, 17 patients (5.8%) with 20 subtelomeric imbalances were identified. Six of the aberrations (2%) were classified as causative for the symptoms, because they occurred either de novo in the patients (5 cases) or the aberration were be detected in the patient and an equally affected parent (1 case). The extent of the deletions ranged from 1.8 to approximately 10 Mb, duplications were 1.8 to approximately 5 Mb in size. In 6 patients, the copy number variations (CNVs) were rated as benign polymorphisms, and the clinical relevance of these CNVs remains unclear in 5 patients (1.7%). Therefore, the overall frequency of clinically relevant imbalances ranges between 2% and 3.7% in our cohort. Conclusion This study illustrates that the qPCR/SYBR green technique represents a rapid and versatile method for the detection of subtelomeric imbalances and the option to map the breakpoint. Thus, this technique is highly suitable for genotype/phenotype studies in patients with MR/developmental delay and/or congenital defects.</p
Räumliches und zeitliches Verteilungsmuster der Immediate Early Gene egr-l und c-fos in der murinen cerebellären Schnittkultur
No full textA 16q12 microdeletion in a boy with severe psychomotor delay, craniofacial dysmorphism, brain and limb malformations, and a heart defect
No full textInterstitial deletions of the proximal chromosome 16q are rare. To date, only six cases with molecularly well-characterized microdeletions within this chromosomal region have been described. We report on a patient with severe psychomotor delay, dysmorphic features, microcephaly and hypoplasia of the corpus callosum, epilepsy, a heart defect, and pronounced muscular hypotonia. Array comparative genomic hybridization (aCGH) revealed that the patient's features were likely caused by a 4.7 Mb de novo deletion on chromosome 16q12.1q12.2, which was confirmed by quantitative real-time PCR (qPCR). The psychomotor delay and craniofacial dysmorphism are more severe in our patient than previously reported patients. Unmasked recessive mutations in the ZNF423 and FTO genes on the remaining allele were excluded as the putative cause for this severe phenotype. In conclusion, the phenotypic spectrum of microdeletions in 16q12 is broad and comprises variable degrees of psychomotor delay and intellectual disability, craniofacial anomalies, and additional features, including heart defects, brain malformations, and limb anomalies. (C) 2011 Wiley Periodicals, Inc
An unbalanced translocation resulting in a duplication of Xq28 causes a Rett syndrome-like phenotype in a female patient
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