Homozygosity for the pathogenic RET hotspot variant p.Cys634Trp: A consanguineous family with MEN2A.

Multiple endocrine neoplasia type 2 (MEN2) is a dominantly inherited condition with defined correlations between the genetic variant and clinical presentations. The location of pathogenic variants in the RET gene is a significant determinant of disease presentation and is associated with variable gene activation. Heterozygous pathogenic variants in codon 634 result in earlier onset of medullary thyroid carcinoma and higher incidence of phaeochromocytoma.

The common TMC1 mutation c.100C>T (p.Arg34X) is not a significant cause of deafness in British Asians.

TMC1, a second-tier deafness gene below GJB2, is an appreciable cause of recessive nonsyndromic hearing loss (DFNB7/11) in North Africa, the Middle East, and parts of South Asia. Additionally, a single founder mutation, c.100C>T (p.

Low prevalence of DFNB1 (connexin 26) mutations in British Pakistani children with non-syndromic sensorineural hearing loss.

Objective: To determine the clinical sensitivity of DFNB1 genetic testing (analysis of the connexin 26 gene GJB2) for non-syndromic sensorineural hearing loss (SNHL) in British Pakistani children and extend to a comparison with British White children and literature data.

Design: Retrospective cohort study.

Setting: City of Bradford, UK.

FNA cytology of collagenous spherulosis: recognizing a benign breast lesion.

This paper describes our recent experience with one case of collagenous spherulosis of the breast which was diagnosed accurately by fine-needle aspiration (FNA) cytology. Histochemical and immunohistochemical studies were performed on the biopsy material. This curious lesion was found in association with benign proliferative breast processes but it can be found in association with both benign and malignant lesions in other organs and breast malignancies.

Enlarged parietal foramina caused by mutations in the homeobox genes ALX4 and MSX2: from genotype to phenotype.

Heterozygous mutations of the homeobox genes ALX4 and MSX2 cause skull defects termed enlarged parietal foramina (PFM) and cranium bifidum (CB); a single MSX2 mutation has been documented in a unique craniosynostosis (CRS) family. However, the relative mutational contribution of these genes to PFM/CB and CRS is not known and information on genotype-phenotype correlations is incomplete. We analysed ALX4 and MSX2 in 11 new unrelated cases or families with PFM/CB, 181 cases of CRS, and a single family segregating a submicroscopic deletion of 11p11.

Alx4 and Msx2 play phenotypically similar and additive roles in skull vault differentiation.

Alx4 and Msx2 encode homeodomain-containing transcription factors that show a clear functional overlap. In both mice and humans, loss of function of either gene is associated with ossification defects of the skull vault, although the major effect is on the frontal bones in mice and the parietal bones in humans. This study was undertaken to discover whether Alx4 and Msx2 show a genetic interaction in skull vault ossification, and to test the hypothesis that they interact with the pathway that includes the Fgfr genes, Twist1 and Runx2.

Parietal foramina with cleidocranial dysplasia is caused by mutation in MSX2.

The combination of skull defects in the form of enlarged parietal foramina (PFM) and deficient ossification of the clavicles is known as parietal foramina with cleidocranial dysplasia (PFMCCD). It is considered to be distinct from classical cleidocranial dysplasia (CCD) and is listed as a separate OMIM entry (168550). So far, only two families have been reported and the molecular basis of the disorder is unknown.

Quantitation of X-Y homologous genes in patients with schizophrenia by multiplex polymerase chain reaction.

Objectives: The genetic basis of schizophrenia is obscure. In an XX male patient with schizophrenia we previously showed that one X;Y translocation breakpoint was in pseudoautosomal region 1 (PAR1) with the effect that the proximal segment of PAR1 from the PAR1 boundary to acetylserotonin N-methyl transferase (ASMT) distally was triplicated in this patient. This study determined whether dosage imbalances of X-Y homologous regions in general are associated with schizophrenia.

The sympathoadrenal system mediates the blood pressure and cardiac effects of human coagulation factor XII-related "new pressor protein".

Objective: To investigate the major cardiovascular effects of human plasma "new pressor protein" (NPP) and how the adrenal medulla contributes to these effects.

Methods: NPP was injected into bioassay rats intravenously, and the effects on blood pressure and cardiac function were investigated. Acute adrenal medullectomy (2MDX), alpha- and beta-adrenergic blockade and plasma catecholamine levels were also used to evaluate the role of the sympathoadrenal system in mediating the NPP effects.

ZNF232: structure and expression analysis of a novel human C(2)H(2) zinc finger gene, member of the SCAN/LeR domain subfamily.

We have identified a novel zinc finger gene, ZNF232, mapped to human chromosome 17p12. The coding region of the gene is organized in three exons corresponding to a 417 amino acid long polypeptide containing a SCAN/LeR domain and five C(2)H(2)-type zinc fingers. ZNF232 is possibly a nuclear protein, as suggested by expression analysis of GFP/ZNF232 chimeric constructs.

Haploinsufficiency of the human homeobox gene ALX4 causes skull ossification defects.

Inherited defects of skull ossification often manifest as symmetric parietal foramina (PFM; MIM 168500). We previously identified mutations of MSX2 in non-syndromic PFM and demonstrated genetic heterogeneity. Deletions of 11p11-p12 (proximal 11p deletion syndrome, P11pDS; MIM 601224) are characterized by multiple exostoses, attributable to haploinsufficiency of EXT2 and PFM.

Potent 'new pressor protein' related to coagulation factor XII is potentiated by inhibition of angiotensin converting enzyme.

Background: 'New pressor protein' was observed after tryptic activation of human and rat plasma in vitro, which is done conventionally for prorenin measurements.

Results: It is potently pressor, heat labile, possesses enzyme activity, and has a relative molecular mass > 30 kDa with isoelectric point(s) 4.7-4.

Potent blood pressure raising effects of activated coagulation factor XII.

A new pressor protein (NPP) in trypsin-activated human plasma was recently reported, whose blood pressure raising effects in bioassay rats are potentiated 300% after treatment with angiotensin I converting enzyme inhibitors (captopril). Pure NPP showed good N-terminal sequence homology with coagulation factor beta FXIIa, and little of it was present in FXII-deficiency plasmas (> or = 99%, n = 4). The present experiments confirm this in four additional FXII-deficiency plasmas.

Retrieval of DNA sequences present at an extremely low frequency.

We describe a method for retrieving sequences with one or two point mutations of a given target sequence, which are present in a DNA population at a frequency of 1 in 466 x 10(3) and 1 in 28 x 10(3) molecules, respectively. By stringent hybridization to a stable, chemically immobilized probe, a large excess of unrelated fragments is removed, and the bound sequences are dissociated and amplified. By repeating the hybridization-amplification cycles twice, we achieved an estimated enrichment of 404,000-fold and 1612-fold, respectively, which was confirmed by cloning the resultant products and sequencing 35 clones.

The yeast Fre1p/Fre2p cupric reductases facilitate copper uptake and are regulated by the copper-modulated Mac1p activator.

Fre1p and Fre2p are ferric reductases which account for the total plasma membrane associated activity, a prerequisite for iron uptake, in Saccharomyces cerevisiae. The two genes are transcriptionally induced by iron depletion. In this communication, we provide evidence that Fre2p has also cupric reductase activity, as has been previously shown for Fre1p (Hassett, R.