Tall stature and minor facial dysmorphisms in a patient with a 17.5 Mb interstitial deletion of chromosome 13 (q14.3q21.33): clinical report and review.

We present a 4-year-old boy with developmental delay and several into minor dysmorphic features due to an interstitial deletion of 17.5 Mb on the long arm of chromosome 13 [46,XY,del (13)(q14.3q21.

C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy.

Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle-age onset. In nine families, we identified heterozygous C-terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease activity but lose normal perinuclear localization.

Klinefelter's syndrome and Prader-Willi syndrome: a rare combination.

In this paper a review is presented of the rare combination of Klinefelter's syndrome and Prader-Willi syndrome (PWS) and a second case of this combination with a uniparental disomy (UPD) etiology of PWS is described. Patients outlined in all other 8 reports and the present case have a PWS phenotype. Virtually no information is available on the behavioral and psychopathological phenotype in this combination.

Homozygosity for a FBN1 missense mutation: clinical and molecular evidence for recessive Marfan syndrome.

Marfan syndrome (MFS) is known as an autosomal-dominant connective tissue disorder (MIM 154,700), involving primarily the skeletal, ocular and cardiovascular systems, and caused by mutations in the gene for fibrillin1 (FBN1). Here, we report on two cousins from a consanguineous family with a homozygous c.1,453C>T FBN1 mutation (p.

A novel microdeletion in 1(p34.2p34.3), involving the SLC2A1 (GLUT1) gene, and severe delayed development.

A de novo 4.1-megabase microdeletion of chromosome 1p34.2p34.

First case of compound heterozygosity in Na,K-ATPase gene ATP1A2 in familial hemiplegic migraine.

Familial hemiplegic migraine (FHM) is a rare autosomal-dominant subtype of migraine with aura, associated with hemiparesis during the aura. Here we describe a unique FHM family in which two novel allelic missense mutations in the Na,K-ATPase gene ATP1A2 segregate in the proband with hemiplegic migraine. Both mutations show reduced penetrance in family members of the proband.

Complex chromosome 17p rearrangements associated with low-copy repeats in two patients with congenital anomalies.

Recent molecular cytogenetic data have shown that the constitution of complex chromosome rearrangements (CCRs) may be more complicated than previously thought. The complicated nature of these rearrangements challenges the accurate delineation of the chromosomal breakpoints and mechanisms involved. Here, we report a molecular cytogenetic analysis of two patients with congenital anomalies and unbalanced de novo CCRs involving chromosome 17p using high-resolution array-based comparative genomic hybridization (array CGH) and fluorescent in situ hybridization (FISH).

A t(4;6)(q12;p23) translocation disrupts a membrane-associated O-acetyl transferase gene (MBOAT1) in a patient with a novel brachydactyly-syndactyly syndrome.

Here, we report a patient with a novel brachydactyly-syndactyly syndrome and a de novo translocation 46,XY,t(4;6)(q12;p23). We mapped the breakpoint and identified genes in the breakpoint region. One of the genes on chromosome 6, the membrane-associated O-acetyl transferase gene 1 (MBOAT1), was disrupted by the breakpoint.

The novel p.L1649Q mutation in the SCN1A epilepsy gene is associated with familial hemiplegic migraine: genetic and functional studies. Mutation in brief #957. Online.

Familial hemiplegic migraine (FHM) is a severe subtype of migraine with hemiparesis during attacks. We scanned 10 families with FHM without mutations in the CACNA1A (FHM1) and ATP1A2 (FHM2) genes. We identified the novel p.

Characterization of a recurrent 15q24 microdeletion syndrome.

We describe multiple individuals with mental retardation and overlapping de novo submicroscopic deletions of 15q24 (1.7-3.9 Mb in size).

Alternating hemiplegia of childhood: no mutations in the glutamate transporter EAAT1.

Alternating hemiplegia of childhood (AHC) is a severe brain disorder, mainly characterised by episodes of hemiplegia, progressive mental retardation, and other severe paroxysmal and permanent neurological symptoms. Clinically and genetically, there is some overlap with sporadic (SHM) and familial (FHM) hemiplegic migraine, a severe monogenic subtype of migraine. Although no mutations were detected in the FHM1 CACNA1A and FHM2 ATP1A2 genes in sporadic AHC patients, a mutation was found in the FHM2 ATP1A2 gene in a family with AHC.

Mutation frequencies of X-linked mental retardation genes in families from the EuroMRX consortium.

The EuroMRX family cohort consists of about 400 families with non-syndromic and 200 families with syndromic X-linked mental retardation (XLMR). After exclusion of Fragile X (Fra X) syndrome, probands from these families were tested for mutations in the coding sequence of 90 known and candidate XLMR genes. In total, 73 causative mutations were identified in 21 genes.

A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism.

Submicroscopic genomic copy number changes have been identified only recently as an important cause of mental retardation. We describe the detection of three interstitial, overlapping 17q21.31 microdeletions in a cohort of 1,200 mentally retarded individuals associated with a clearly recognizable clinical phenotype of mental retardation, hypotonia and a characteristic face.

Redox-active iron released during machine perfusion predicts viability of ischemically injured deceased donor kidneys.

Redox-active iron, catalyzing the generation of reactive oxygen species, has been implicated in experimental renal ischemia-reperfusion injury. However, in clinical transplantation, it is unknown whether redox-active iron is involved in the pathophysiology of ischemic injury of non-heart-beating (NHB) donor kidneys. We measured redox-active iron concentrations in perfusate samples of 231 deceased donor kidneys that were preserved by machine pulsatile perfusion at our institution between May 1998 and November 2002 using the bleomycin detectable iron assay.

Pex14p is not required for N-starvation induced microautophagy and in catalytic amounts for macropexophagy in Hansenula polymorpha.

We showed before that the two oppositely directed processes of peroxisome biogenesis and selective peroxisome degradation (macropexophagy) converge at the peroxisomal membrane protein Pex14p. Here we show that this protein is not required for peroxisome degradation during nitrogen starvation-induced general autophagy, thereby limiting its function to the selective degradation process. Pex14p is present in two forms, namely an unmodified (Pex14p) and a phosphorylated form (Pex14p(Pi)) that are differently induced during peroxisome proliferation.

Genetic biomarkers for migraine.

Biomarkers are physical signs or laboratory measurements that occur in association with a pathological process and have putative diagnostic and/or prognostic utility. In migraine, clinical, radiological, and biochemical biomarkers might be helpful to improve diagnosis, get insight in pathophysiology, and facilitate treatment choices. Genetic biomarkers are defined as genetic variations (mutations or polymorphisms) that can predict disease susceptibility, disease outcome, or treatment response.

Holoprosencephaly and preaxial polydactyly associated with a 1.24 Mb duplication encompassing FBXW11 at 5q35.1.

Holoprosencephaly (HPE) is the most common developmental defect affecting the forebrain and midface in humans. The aetiology of HPE is highly heterogeneous and includes both environmental and genetic factors. Here we report on a boy with mild mental retardation, lobar HPE, epilepsy, mild pyramidal syndrome of the legs, ventricular septal defect, vesicoureteral reflux, preaxial polydactyly, and facial dysmorphisms.

European Cytogeneticists Association Register of Unbalanced Chromosome Aberrations (ECARUCA); an online database for rare chromosome abnormalities.

During recent years a considerable improvement in diagnostic techniques has enabled cytogeneticists to find more and smaller chromosomal aberrations. However, accurate clinical knowledge about rare chromosome disorders is frequently lacking, mostly due to a significant decline in publishable cases. On the other hand, there is an increasing demand from parents and physicians for reliable information.

Loss-of-function mutations in euchromatin histone methyl transferase 1 (EHMT1) cause the 9q34 subtelomeric deletion syndrome.

A clinically recognizable 9q subtelomeric deletion syndrome has recently been established. Common features seen in these patients are severe mental retardation, hypotonia, brachycephaly, flat face with hypertelorism, synophrys, anteverted nares, cupid bow or tented upper lip, everted lower lip, prognathism, macroglossia, conotruncal heart defects, and behavioral problems. The minimal critical region responsible for this 9q subtelomeric deletion (9q-) syndrome has been estimated to be <1 Mb and comprises the euchromatin histone methyl transferase 1 gene (EHMT1).

A novel 2.3 Mb microduplication of 12q24.21q24.23 detected by genome-wide tiling-path resolution array comparative genomic hybridization in a girl with syndromic mental retardation.

We report on a female patient with severe mental retardation, dysmorphic features, deafness, spasticity, and behavioural problems in whom a 2.3 Mb duplication of 12q24.21q24.

Rapid pulmonary expression of acute-phase reactants after local lipopolysaccharide exposure in mice is followed by an interleukin-6 mediated systemic acute-phase response.

This study investigated local and systemic innate immune responses in lipopolysaccharide (LPS)-induced lung inflammation in mice. Intratracheal LPS exposure resulted in increased pulmonary mRNA expression for acute-phase reactants (APRs) alpha(1)-antitrypsin (alpha(1)-AT), alpha(1)-acid glycoprotein (AGP), and LPS-binding protein (LBP) from 4 hours post exposure. Although pulmonary serum amyloid P component (SAP) mRNA was not increased, systemic levels of SAP, AGP, and LBP were elevated from 24 hours post exposure.