Further delineation of the SATB2 phenotype.

SATB2 is an evolutionarily highly conserved chromatin remodeling gene located on chromosome 2q33.1. Vertebrate animal models have shown that Satb2 has a crucial role in craniofacial patterning and osteoblast differentiation, as well as in determining the fates of neuronal projections in the developing neocortex.

Macrocephaly, obesity, mental (intellectual) disability, and ocular abnormalities: alternative definition and further delineation of MOMO syndrome.

MOMO syndrome, previously defined as Macrosomia, Obesity, Macrocephaly, and Ocular abnormalities (OMIM 157980) is a rare intellectual disability syndrome of unknown cause. We describe two further patients with MOMO syndrome. Reported data of patients with MOMO syndrome and our own findings indicate that overgrowth does not appear to be a specific feature.

[Genetic analysis of a supernumerary derivative chromosome 15].

Objective: To detect and analyze a supernumerary derivative chromosome 15 with combined cytogenetic and molecular techniques, and to discuss the correlation between genomic copy number variations (CNVs) and clinical phenotypes.

Methods: G-banded chromosome analysis and multiplex ligation-dependent probe amplification (MLPA) were carried out. The whole genome of the patient was also analyzed with array-comparative genome hybridization(array-CGH).

A homozygous microdeletion within ADAMTSL4 in patients with isolated ectopia lentis: evidence of a founder mutation.

Purpose: The purpose of the study was to look for ADAMTSL4 mutations in a cohort of German patients with isolated ectopia lentis from nonconsanguineous families.

Methods: Mutation screening was performed by PCR amplification of the coding exons of ADAMTSL4 and subsequent sequencing.

Results: An identical homozygous deletion of 20 bp of coding sequence within exon 6 (NM_019032.

Supreme worth of clinical epidemiology in Africa:bancroftian Filariasis as just one case in point.

Clinical epidemiology is going to be the Discipline par excellence of the next century, if not the millennium. Coming as it does from one who has spent decades in clinical medicine and therapeutics, this is a bold statement. Clinical epidemiology answers the questions what? Where? How? When? Who? Why? And Which? In matters of health and disease.

Identification of the human/mouse syntenic common fragile site FRA7K/Fra12C1--relation of FRA7K and other human common fragile sites on chromosome 7 to evolutionary breakpoints.

Common fragile sites (CFSs) are expressed as chromosome gaps in cells of different species including human and mouse as a result of the inhibition of DNA replication. They may serve as hot spots for DNA breakage in processes such as tumorigenesis and chromosome evolution. Using multicolor fluorescence in situ hybridization mapping, the authors describe here human CFS FRA7K on chromosome band 7q31.

Common fragile sites are conserved features of human and mouse chromosomes and relate to large active genes.

Common fragile sites (CFSs) are seen as chromosomal gaps and breaks brought about by inhibition of replication, and it is thought that they cluster with tumor breakpoints. This study presents a comprehensive analysis using conventional and molecular cytogenetic mapping of CFSs and their expression frequencies in two mouse strains, BALB/c and C57BL/6, and in human probands. Here we show that induced mouse CFSs relate to sites of spontaneous gaps and breaks and that CFS expression levels in chromosome bands are conserved between the two mouse strains and between syntenic mouse and human DNA segments.

Biochemical data in ornithine transcarbamylase deficiency (OTCD) carrier risk estimation: logistic discrimination and combination with genetic information.

One-fifth of the gene mutations causing ornithine transcarbamylase deficiency cannot be detected. In such cases carrier risk estimation must refer to biochemical data-such as increased plasma glutamine concentration or increased orotidine excretion after allopurinol load -although these parameters do not yield a definite diagnosis. Here, I derive odds for carrier risk estimation from published data, i.

Supernumerary marker chromosome 7 and maternal uniparental disomy 7 in a boy with growth retardation and triangular face.

We report on a 12-month-old boy with pre and post-natal growth retardation, triangular face and mild psychomotor retardation. Karyotyping revealed a supernumerary marker chromosome (SMC) in 36% of cells. Using fluorescence in situ hybridization and BAC clones, the supernumerary marker chromosome was found to be a highly deleted chromosome 7 with breakpoints within the pericentric euchromatin (partial trisomy 7).

Recurrent chromosomal aberrations in INK4a/ARF defective primary lymphomas predict drug responses in vivo.

Predicting responsiveness to anticancer therapy based on molecular findings at diagnosis is important to optimize treatment decisions. Although clinical outcome correlates with distinct mutations in some cancer entities, treatment responses within these lesion-stratified subgroups still remain heterogeneous, underscoring the need for additional prognosticators. We previously demonstrated that defined genetic defects at the INK4a/ARF locus, which encodes the tumor suppressors p16INK4a and ARF, not only accelerated lymphomagenesis in the Emu-myc transgenic mouse but also interfered with treatment sensitivity.

First-trimester screening: an overview.

An improvement in prenatal screening for chromosomal defects has been achieved by combining sonography and biochemical markers. Analyzing markers taken from maternal blood such as pregnancy-associated plasma protein A and free beta-human chorionic gonadotropin in combination with the ultrasound marker nuchal translucency provides detection rates of 90% for the most important chromosomal anomalies. In addition, nuchal translucency is a marker for severe heart defects.

High-resolution analysis of chromosomal imbalances using the Affymetrix 10K SNP genotyping chip.

Array-based comparative genome hybridization is a powerful tool for detecting chromosomal imbalances at high resolution. However, the design and setup of such arrays are time consuming and expensive and thus worthwhile only when large numbers of arrays will be processed. To provide a feasible solution, we have developed an algorithm that renders the publicly available Affymetrix 10K SNP genotyping chip useful for high-resolution analysis of chromosomal imbalances.

Subtelomere FISH in 50 children with mental retardation and minor anomalies, identified by a checklist, detects 10 rearrangements including a de novo balanced translocation of chromosomes 17p13.3 and 20q13.33.

Submicroscopic or subtle aneusomies at the chromosome ends, typically diagnosed by subtelomere fluorescence in situ hybridization (FISH), are a significant cause of idiopathic mental retardation (MR). Some 20 subtelomere studies, including more than 2,500 subjects, have been reported. The studies are not directly comparable because different techniques and patient ascertainment criteria were used, but an analysis of 14 studies showed that aberrations were detected in 97 out of 1,718 patients (5.

Familial pancreatic cancer.

The dismal prognosis of ductal pancreatic adenocarcinoma is mainly attributable to advanced tumor stages at the time of diagnosis. Meanwhile, familial pancreatic cancer is an established hereditary tumor entity that is responsible for approximately 3% of pancreatic cancer (PC) cases. Therefore, analysis of the family history may help to identify individuals at increased risk of developing PC.

Clinical, cytogenetic and molecular investigation in a fetus with Wolf-Hirschhorn syndrome with paternally derived 4p deletion. Case report and review of the literature.

Wolf-Hirschhorn (4p-) syndrome (WHS), caused by partial deletion of the short arm of chromosome 4, has been extensively described in children and young adults. Knowledge on fetuses with WHS is still limited due to the small number of published cases. We report on a fetus with prenatally diagnosed severe intrauterine growth retardation, reduced thoracal diameter, clubfeet deformity and midface hypoplasia including slight microretrognathia indicative for fetal karyotyping.

Hypertrichosis, hyperkeratosis, abnormal corpus callosum, mental retardation and dysmorphic features in three unrelated females.

We report three unrelated patients with hypertrichosis, mild to moderate mental retardation, and dysmorphic facial features including low anterior hairline, thick arched eyebrows, nose with broad tip and columella below alae nasi, short philtrum, thick drooping lower lip and simple posteriorly rotated ears. They also had rough skin with hyperkeratotic plaques. Feet and finger tips were broad.

Retinoblastoma, pinealoma, and mild overgrowth in a boy with a deletion of RB1 and neighbor genes on chromosome 13q14.

We report on a 10-year-old boy with a normal karyotype and a chromosome 13q14 deletion of the retinoblastoma gene (RB1) by fluorescence in situ hybridization (FISH). He showed subtle signs of overgrowth, including macrocephaly, hepatomegaly, and inguinal hernia. The boy also had cryptorchism and mild developmental delay.

Familial optic atrophy with white matter changes.

We report two brothers who suffer from infantile onset optic atrophy and blindness. MRI of the brain demonstrated periventricular white matter changes in both children. Neurological and developmental examination are normal.

Mutational spectrum in German patients with phenylalanine hydroxylase deficiency.

We report on the spectrum and frequency of mutations in the phenylalanine hydroxylase (PAH) gene in 226 German families with PAH deficiency, most of them from Southern Germany. A total of 88 mutations were identified in 428 out of 438 mutant PAH alleles including one novel stop mutation L293X (c.878T>A).

Computer aided analysis of additional chromosome aberrations in Philadelphia chromosome positive acute lymphoblastic leukaemia using a simplified computer readable cytogenetic notation.

Background: The analysis of complex cytogenetic databases of distinct leukaemia entities may help to detect rare recurring chromosome aberrations, minimal common regions of gains and losses, and also hot spots of genomic rearrangements. The patterns of the karyotype alterations may provide insights into the genetic pathways of disease progression.

Results: We developed a simplified computer readable cytogenetic notation (SCCN) by which chromosome findings are normalised at a resolution of 400 bands.

Molecular cytogenetic characterization of a 10p14 deletion that includes the DGS2 region in a patient with multiple anomalies.

We report on a prenatally diagnosed four-month-old boy with DiGeorge-like phenotype and a deletion of chromosome 10pter --> 14. Fluorescence in situ hybridization (FISH) experiments using phage artificial chromosome (PAC) and yeast artificial chromosome (YAC) clones indicated that the chromosomal breakpoint was located at the proximal boundary of the DiGeorge syndrome 2 (DGS2) critical region. The patient demonstrated a high forehead, high arched eyebrows, short palpebral fissures, sparse eyelashes, prominent nose with bulbous tip, small mouth, receding chin, round ears with deficient helices, cardiac defects atrial septal defect (ASD), ventricular septal defect (VSD), mild brachytelephalangy, mild syndactyly, hypoplastic left kidney, undescended testes, muscular hypertonia, dorsally flexed big toes, and developmental delay.

Gene finding in genetically isolated populations.

The struggle to identify susceptibility genes for complex disorders has stimulated geneticists to develop new approaches. One approach that has gained considerable interest is to focus on genetically isolated populations rather than on the general population. There remains much controversy and theoretical debate over the feasibility and advantages of such populations, but recent results speak in favor of the feasibility of this approach, and will be reviewed here.