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We report on scaled finFETs built with a novel routing scheme wherein devices are connected via buried power rails (BPRs) from both wafer sides, with tight variability and matching control. On the wafer’s frontside (FS), M1 lines (FSM1) are connected through V0 vias to M0A lines which are then linked to BPR lines by vias called VBPR while also contacting directly the device’s S/D-epi. As for gate wiring, to enable in this work its access from both wafer sides, gate is also connected to BPR via V0 landing on it and on a neighboring M0A line set only on field-oxide. A single-step metallization for M0A and VBPR is preceded by in situ preclean(s) optimized for improved BPR-VBPR contact interface and ${R}_{\text {ext}}$ , as confirmed electrically and by physical analysis. After FS processing, wafer flipping, bonding, and extreme thinning, highly scaled, ~323 nm deep nano-through-Si-vias (nTSVs) land on BPR, with tight overlay control and unchanged BPR resistance [26%–29% lower with improved tungsten (W)-fill], connecting them to the first backside (BS) metal level (BSM1). By moving the power delivery network to the BS (BSPDN), besides alleviating FS routing congestion, considerably smaller dynamic and static IR drop values are predicted from on- chip power heat maps generated for a low power 64-bit CPU at 2-nm design rules: 82% and 96% less worst-case values versus a reference configuration, respectively. P/NMOS show similar or even superior ${I}_{ \mathrm{\scriptscriptstyle ON}}$ – ${I}_{ \mathrm{\scriptscriptstyle OFF}}$ after BS processing and extra anneal(s) added for ${V}_{T}$ recovery, mobility and bias temperature instability (BTI) improvement—up to 8%/15% higher ${I}_{ \mathrm{\scriptscriptstyle ON}}$ linked to anneal selection.

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4−/−mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases.

Abstract

Mutations in the FGD1gene have been shown to cause Aarskog–Scott syndrome AAS, or faciodigitogenital dysplasia OMIM305400, an Xlinked disorder characterized by distinctive genital and skeletal developmental abnormalities with a broad spectrum of clinical phenotypes. To date, 20 distinct mutations have been reported, but little phenotypic data are available on patients with molecularly confirmed AAS. In the present study, we report on our experience of screening for mutations in the FGD1gene in a cohort of 60 European patients with a clinically suspected diagnosis of AAS. We identified nine novel mutations in 11 patients detection rate of 18.33, including three missense mutations p.R402Q; p.S558W; p.K748E, four truncating mutations p.Y530X; p.R656X; c.806delC; c.1620delC, one inframe deletion c.20202022delGAG and the first reported splice site mutation c.19353A>C. A recurrent mutation p.R656X was detected in three independent families. We did not find any evidence for phenotype–genotype correlations between type and position of mutations and clinical features. In addition to the wellestablished phenotypic features of AAS, other clinical features are also reported and discussed. © 2010 WileyLiss, Inc.

The Prader–Willi syndrome (PWS) is a genetically determined developmental disorder caused by abnormalities of the proximal region of chromosome 15q11-13. In a previous study, we reported that psychotic episodes, occurring in 16% of persons with PWS, had an onset in adolescence, never occurred in persons with paternal deletion, and were exclusively associated with maternal uniparental disomy (UPD) or imprinting abnormalities (IM). In order to gain a better understanding of the psychopathology and to further refine the psychiatric diagnosis, we describe in more detail the psychopathological manifestations of six adults with a history of psychotic episodes. All these individuals had a detailed psychiatric examination, including the use of the operational criteria (OPCRIT) checklist. An identifiable subtype of psychotic disorder was associated with PWS. Characteristics include early age of onset, acute onset, polymorphous, and shifting symptomatology and a need for psychiatric hospitalization. The presence of precipitating stress factors and a prodromal phase with physiological symptoms was reported in all patients. Current diagnostic categories do not allow an unequivocal psychiatric diagnosis. © 2004 Wiley-Liss, Inc.

Greig cephalopolysyndactyly (GCPS) (OMIM 175700) is an autosomal dominant disorder characterized by a distinct combination of craniofacial, hand and foot malformations. In this report, clinical and radiological findings of 12 patients with GCPS derived from 4 independent families and 3 sporadic cases with documented GLI3 mutations are presented with particular emphasis on inter- and intrafamilial variability. In a particularly instructive family in which 9 members of 4 generations could be studied clinically and molecularly, a missense mutation (R625W) is transmitted and shows a partially penetrant pattern. In a branch of the family, the GCPS phenotype skips a generation via a normal female carrier without clinical signs providing evidence that GCPS does not always manifest full penetrance as generally supposed. © 2003 Wiley-Liss, Inc.

We describe a three-generation family with clinical and radiological findings of osteopoikilosis in five and melorheostosis in one individual. The co-occurrence of both rare bone disorders suggests that both conditions might be related as suggested previously by Butkus et al. [1997: Am J Med Genet 72:43–46] and Nevin et al. [1999: Am J Med Genet 82:409–414]. The findings in this family strengthen the hypothesis that osteopoikilosis is an autosomal dominant condition and that an early postzygotic second hit mutation in the second allele results in melorheostosis. © 2003 Wiley-Liss, Inc.

We report a 13-week-old female fetus with early onset fetal akinesia deformation sequence (FADS) and hydranencephaly. In a previous pregnancy, the same ultrasonographic findings were noted at 13 weeks. Fetopathological examination of both female fetuses confirmed FADS with severe arthogryposis, multiple pterygia, and muscular hypoplasia. Neuropathological examination showed massive cystic dilatation of the cerebral ventricles (hydranencephaly) with calcification of the basal ganglion and brain stem and a proliferative vasculopathy throughout the central nervous system. The findings in the two female siblings document the earliest echographic diagnosis of hydranencephaly, Fowler type, and this observation further supports autosomal recessive inheritance of this distinct type of hydranencephaly. © 2002 Wiley-Liss, Inc.

We report the second trimester prenatal diagnosis of severe symmetrical limb deficiencies with posterior fossa cyst and cardiac anomaly in a female fetus. Fetopathological examination revealed additional anomalies: renal-hepatic-pancreatic dysplasia, cleft palate, and Müllerian duct anomaly. The spectrum of congenital malformations in the present observation is difficult to classify into a single syndrome entity and presents an overlap with several syndromes: Roberts syndrome, Goldston syndrome, and renal-hepatic-pancreatic dysplasia. © 2001 Wiley-Liss, Inc.

This was a retrospective study on the results of interphase fluorescence in situ hybridization (FISH), performed routinely for chromosome 21 and on ultrasonographic indications for chromosomes 13, 18, X and Y in a series of 5049 amniotic fluid samples. Interphase FISH for chromosome 21 was performed in 5049 consecutive amniotic fluid samples for the rapid prenatal diagnosis of Down syndrome. Aneuploidy for four other chromosomes (13, 18, X and Y) was tested following ultrasonographic indications. Karyotypes from standard cytogenetic analysis were compared to the FISH results. Using conventional cytogenetics 3.6% (183/5049) chromosomal anomalies were detected. After exclusion of familial chromosome rearrangements, i.e. balanced autosomal reciprocal or Robertsonian translocations (30/5049) and inversions (19/5049), 2.65% chromosomal anomalies (134/5049) were diagnosed. Of this group 0.18% (9/5049) were chromosomal rearrangements not detectable by FISH and 2.47% (125/5049) were numerical chromosomal anomalies detectable by interphase FISH for chromosomes 13, 18, 21, X and Y. With routine interphase FISH for chromosome 21 and FISH on echographic indication for the other four chromosomes we detected 107/125 of these numerical chromosomal anomalies, i.e. 85.6%. All 70 cases of trisomy 21 were detected by FISH and confirmed with conventional cytogenetics (sensitivity=100%) and there were no false-positive results (specificity=100%). Maternal cell contamination of amniotic fluid samples occurred in 1.27% (64/5049) of samples; 0.26% (13/5049) of these samples were uninformative by FISH due to maternal cell contamination (12/5049) or absence of nuclei in one sample (1/5049). In this group of 5049 samples we found that FISH is a reliable technique for the rapid prenatal diagnosis of trisomy 21. The number of uninformative cases due to maternal cell contamination was low. The strategy to perform FISH for chromosome 21 in all samples and only on ultrasonographic indication for the four other chromosomes (13, 18, X and Y) followed by standard cytogenetics is effective. Copyright © 2002 John Wiley & Sons, Ltd.

We present further evidence for autosomal recessive inheritance of the bilateral tibial agenesis/ectrodactyly dysostosis. A consanguineous Turkish couple gave birth to three children with malformations. The first, a boy, died neonatally of pulmonary hypertension with congenital alveolar capillary dysplasia and also had tibial agenesis and ectrodactyly. A second child, a girl, died after birth with the same abnormality of the lungs without skeletal malformations. After the birth of three unaffected children, echographic examination at 15 weeks of gestation in the sixth pregnancy documented agenesis of tibiae and symmetrical ectrodactyly of hands and feet. Autopsy did not show additional malformations, and lung development was normal for gestational age. This observation also confirms the autosomal recessive inheritance pattern of congenital alveolar capillary dysplasia. © 2001 Wiley-Liss, Inc.

We present a patient with heterotaxy and a de novo, apparently balanced reciprocal translocation with breakpoints at 6q21 and 20p13. Another patient with heterotaxy was previously reported with a de novo balanced translocation involving chromosome band 6q21. The breakpoints in both patients on 6q21 were found to be located in the same chromosomal region spanning maximally 2 Mb. We speculate that the two breakpoints lead to the disruption of the function of a single gene, either directly or through long distance effects. Alternatively, the present observation suggests additional heterogeneity in heterotaxy in humans. © 2001 Wiley-Liss, Inc.

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This study presents a family with a syndromic form of X-linked mental retardation in which four males in two generations present severe mental retardation, slowly progressive spastic paraplegia, facial hypotonia, and maxillary hypoplasia. Multipoint linkage analysis with 24 highly polymorphic markers indicated two possible candidate regions: Xp21.1–Xq21.3 (flanking markers DXS1214 and DXS990) and Xq23–Xq27.1 (flanking markers DXS8020 and DXS984). The two known loci for X-linked mental retardation and spastic paraplegia are excluded: proteolipid protein in Xp21 and L1 cell adhesion molecule in Xq28. Therefore, the syndrome in this family appears to represent a previously undescribed X-linked spastic paraplegia-mental retardation syndrome. Am. J. Med. Genet. 94:1–4, 2000. © 2000 Wiley-Liss, Inc.

In this contribution we review current knowledge of the chromosome 22q11 deletion syndrome, with special emphasis on the clinical characteristics, including physical features, cognitive-behavioral spectrum, and psychiatric complications. Am. J. Med. Genet. (Semin. Med. Genet.) 97:128–135, 2000. © 2000 Wiley-Liss, Inc.

We report on a 31-year-old mentally retarded woman with minor facial anomalies and a heteromorphic chromosome 9 with tandem duplication of the 9p11-q13 pericentromeric region. To the best of our knowledge, this is the first report of tandem duplication of this region. An identical chromosome 9 morphology was found in the healthy and phenotypically normal sister of the proposita. The usefulness of double-color FISH techniques and the presumed mechanism accounting for the origin of the chromosomal anomaly and for the phenotypic discordance observed between the two sisters are discussed. Am. J. Med. Genet. 93:192–197, 2000. © 2000 Wiley-Liss, Inc.

The catalyst V2O5/TiO2 (anatase) is an important industrial catalyst for the partial oxidation of hydrocarbons. Its catalytic properties are probably related to a specific interface and surface overlayer structure. Model catalysts of V2O5/TiO2 were prepared by depositing thin V2O5 layers on anatase single-crystal minerals by means of d.c. reactive magnetron sputtering. Azimuthal x-ray photoelectron diffraction (XPD) measurements were performed, recording the Ti 2p3/2, O 1s and V 2p3/2 photoelectron peaks. All azimuthal scans displayed diffraction maxima along the major axes of TiO2, including the V 2p scan, which indicates epitaxy between substrate and sputtered layer. This paper presents single scattering calculations based on several literature models for the structure of vanadium oxide upon anatase. These models have been tested for the presence of intensity maxima along TiO2 major axes in their theoretical azimuthal Ti 2p, O 1s and V 2p intensity patterns. Comparison of simulations and experiment points to a flattened VO layer upon the anatase substrate as the better model. Copyright © 2000 John Wiley & Sons, Ltd.

The catalyst V2O5/TiO2(anatase) is an important industrial catalyst for the partial oxidation of hydrocarbons. Its catalytic properties are probably related to a specific interface and surface overlayer structure. Model catalysts of V2O5/TiO2were prepared by depositing thin V2O5layers on anatase single‐crystal minerals by means of d.c. reactive magnetron sputtering. Azimuthal x‐ray photoelectron diffraction (XPD) measurements were performed, recording the Ti 2p3/2, O 1s and V 2p3/2photoelectron peaks. All azimuthal scans displayed diffraction maxima along the major axes of TiO2, including the V 2p scan, which indicates epitaxy between substrate and sputtered layer. This paper presents single scattering calculations based on several literature models for the structure of vanadium oxide upon anatase. These models have been tested for the presence of intensity maxima along TiO2major axes in their theoretical azimuthal Ti 2p, O 1s and V 2p intensity patterns. Comparison of simulations and experiment points to a flattened VO layer upon the anatase substrate as the better model. Copyright © 2000 John Wiley & Sons, Ltd.

Ninety-six adults with Down syndrome (DS) from an institutional setting of 591 mentally retarded were investigated systematically with respect to cytogenetic diagnosis, mental functioning and dementia, ophthalmological and audiological abnormalities, and thyroid function. Seventy of the 96 DS patients (73%) were older than 40 years. Only 4.2% were females. Trisomy 21 was found in 86% and mosaic trisomy 21 in 13%. Eighty-two percent of the patients were moderately or severely mentally retarded, 15% were profoundly retarded, and only 3% mildly retarded. Nineteen percent of the patients had dementia. This number increased to 42% of the patients above the age of 50 years. Epileptic seizures were present in 16.7% of all patients, and in 50% of the patients with dementia. Only 17% of the patients in the present study had normal visual acuity, one-third had at least moderately reduced vision. This number increased significantly with age: in the age group 50–59 years almost half of the patients had moderate to severe vision loss. Seventy percent of the patients had moderate, severe, or very severe hearing loss, which was undiagnosed before systematic hearing testing was performed. Increased (48%) or decreased (1%) TSH level was found in 49% of the patients examined for thyroid functions. We suggest a regular screening of all adults with DS to diagnose early dementia, epilepsy, hypothyroidism, and early loss of visual acuity and hearing, with special attention to the group of patients who are severely to profoundly mentally retarded and those with advanced age. Cytogenetic studies are necessary to confirm the clinical diagnosis and are essential for genetic counseling purposes. Am. J. Med. Genet. 85:376–384, 1999. © 1999 Wiley-Liss, Inc.

Dyskeratosis congenita (DC) is a rare inherited disorder characterised by the early onset of reticulate skin pigmentation, nail dystrophy, and mucosal leucoplakia. In over 80% of cases bone marrow failure develops and this is the main cause of early mortality. The DC1 gene responsible for the X linked form (MIM 305000) of dyskeratosis congenita has been mapped to Xq28. In order to narrow the candidate gene region, genetic linkage analysis was performed in eight X linked pedigrees using a set of markers spanning Xq28. A maximum lod score of 5.31 with no recombinations was achieved with marker DXS1073. Two recombination events were identified; one of these uses X chromosome inactivation pattern analysis to determine carrier status and haplotype analysis to fine map the recombination breakpoint. The fine mapping of these recombination events has enabled the candidate gene region for X linked dyskeratosis congenita to be defined as the 1.4 Mb interval between Xq3274 and DXS1108.

The PAX2 gene is mutated in patients with ocular colobomas, vesicoureteral reflux (VUR), and kidney anomalies (renal-coloboma syndrome, OMIM 120330). The three abnormalities which make up this syndrome also occur in isolation, but the causal genes are not known. PAX2 encodes a transcription factor of the paired box class of DNA binding proteins, important for the development of the urogenital tract, optic nerve and adjacent retina, inner ear, and CNS. In this paper we have investigated the prevalence of PAX2 mutations in patients with ocular colobomas, microphthalmos, or retinal anomalies, either in isolation or with associated urogenital anomalies. Using PCR-SSCP, most or all exons of PAX2 were examined in blood DNA from 99 patients who have either ocular anomalies alone or a combination of ocular and urogenital conditions. PAX2 mutations were not detected in patients with ocular colobomas, either in isolation or with associated abnormalities, except in one patient with typical renal-coloboma syndrome. We conclude that PAX2 mutations are unlikely to be common in patients with ocular colobomas in isolation or in patients with ocular colobomas and associated anomalies, except for patients with typical renal-coloboma syndrome where PAX2 is known to be the aetiological cause.

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We describe a patient with a de novo chromosomal aberration with karyotype 46,XY,10q+, presenting clinical features of partial duplication of distal chromosome 10q. Further studies using microsatellites and FISH showed a triplication of distal chromosome 10q. The rearrangement involved both maternal homologues and the middle chromosomal 10q fragment of the triplication was inverted, similar to previously reported chromosomal triplications. Chromosomal triplications may be more frequent than assumed and may share a common molecular mechanism.

We report 2 families with X‐linked infantile spasms syndrome (X‐linked West syndrome). Data from clinical examination, biochemical analysis, neuroimaging, and neuropathology are discussed. In these families, genetic linkage analysis was able to locate the disease gene to the distal part of the short arm of the X chromosome, between Xpter and Xp11.4. This is the first report of linkage with genetic markers in this disorder. Although most cases are sporadic, further unraveling of the genetic background of the familial cases might greatly improve our understanding of infantile spasms.

Two families with nonspecific X-linked mental retardation (XLMR) are presented. In the first family, MRX49, 5 male patients in 2 generations showed mild to moderate mental retardation. Two-point linkage analysis with 28 polymorphic markers, dispersed over the X-chromosome, yielded a maximal LOD score of 2.107 with markers DXS7107 and DXS8051 at θ = 0.0, localizing the MRX49 gene at Xp22.3-p22.2, between Xpter and marker DXS8022. Multipoint linkage analysis showed negative LOD values over all other regions of the chromosome. In the second family, MRX50, 4 males in 2 generations showed moderate mental retardation. Pairwise linkage analysis with 28 polymorphic markers yielded a LOD score of 2.056 with markers DXS8054, DXS1055, and DXS1204, all at θ = 0.0. Flanking markers were DXS8012 and DXS991, situating the MRX50 gene at Xp11.3-Xp11.21, in the pericentromeric part of the short arm of the X chromosome. Am. J. Med. Genet. 73:474–479, 1997. © 1997 Wiley-Liss, Inc.

Serum levels of pregnancy zone protein were measured in children with growth hormone deficiency and in girls with Turner syndrome, before and during treatment with recombinant human growth hormone and in healthy controls. The pregnancy zone protein serum levels in growth hormone deficiency patients before treatment were significantly higher than in controls (median value 2420 μg/l vs 434 μg/l; p≤0.001). In Turner syndrome patients they were within the normal range. The administration of rhGH to both growth hormone deficiency and Turner syndrome patients resulted in a significant decrease in the serum pregnancy zone protein levels by approximately 50%. The addition of 50 ng·kg−1·d −1ethinylestradiol to the growth hormone treatment in Turner syndrome patients led to an increase in pregnancy zone protein concentrations in four out of five patients. Elevated pregnancy zone protein levels were also found in two children with growth hormone resistance (Laron type dwarfism). In one patient with placental growth hormone deficiency, pregnancy zone protein serum levels during pregnancy were within the normal range. These results suggest that the serum pregnancy zone protein levels are down-regulated by growth hormone.

Abstract: We present a family with autosomal-dominant inheritance of renal insufficiency caused by renal hypoplasia in six individuals. In all affected individuals, signs of optic disk dysplasia were detected, but most patients were asymptomatic. A heterozygous missense mutation in the PAX2 gene causing a Gly75 to Ser substitution was present in all affected individuals. A second, unrelated patient presented with ocular complaints related to optic disk dysplasia, and had a history of vesico-ureteral reflux. A heterozygous hexanucleotide duplication in the PAX2 gene was detected leading to the duplication of GluThr at positions 74 and 75. The mutations in these two families are the first mutations in the PAX2 gene that do not lead to a truncated protein. Mechanistically, these mutations are expected to result in abnormal folding of the PAX2 protein. These observations further expand the spectrum of clinical features associated with PAX2 mutations, and suggest that a distinct genetic disorder can be identified in patients with renal dysplasia through a careful eye examination. As the ocular manifestations in this syndrome are variable anomalies of retinal and optic disk dysplasia, we prefer the term “papillo-renal syndrome”.

Genomic clones containing the exons coding for the bait domain of human pregnancy zone protein and α2macroglobulin were isolated and fragments containing the bait exons were sequenced. It is shown that the bait domains of both α2macroglobulin and pregnancy zone protein are encoded by two exons, with conserved exon/intron boundaries. A genetic polymorphism showing either a Met or a Val residue as the sixth amino acid of the pregnancy zone protein bait domain was detected with the rare Met allele showing a gene frequency of 0.065.

Hydronephrosis caused by pelvi-ureteric junction obstruction (PUJO) is a frequent urological malformation assumed to result from a deficient development of the ureteric bud. The exact etiology of pelvi-ureteric junction stenosis is unknown, but there is convincing evidence for a genetic cause, with linkage analysis predicting a hereditary hydronephrosis locus on chromosome 6p. We encountered a patient with a de novo autosomal t(6;19)(p21;q13.1) and attendant bilateral multicystic renal dysplasia (MRD), bilateral PUJO resulting in massive hydronephrosis, and an associated von Mayer-Rokitansky-Küster disorder. On the basis of the presumption that in this patient the putative hydronephrosis gene might be disrupted by the translocation, we sought to isolate DNA from the breakpoint regions as the initial step in a strategy to identify genes affected by the t(6;19). Using sequential rounds of fiuorescence in situ hybridization (FISH) with cosmids selected from a detailed integrated map of the long arm of chromosome 19, we have identified a cosmid clone that spans the breakpoint. The position of the breakpoint was further localized by Southern blot analysis. Using a vectorette PCR approach, rearranged DNA fragments were isolated and, by comparative nucleotide sequence analysis, these were shown to contain ectopic sequences. A cosmid clone containing these ectopic sequences was isolated and shown by CASH (chromosome assignment using somatic cell hybrids) and FISH (fluorescence in situ hybridization) analysis to map to the short arm of chromosome 6 and to span the breakpoint found in the MRD patient. The isolated cosmid clones are useful reagents for analysis of other MRD patients and for the search for genes at or flanking the breakpoints.

Genomic clones containing the exons coding for the bait domain of human pregnancy zone protein and α 2macroglobulin were isolated and fragments containing the bait exons were sequenced. It is shown that the bait domains of both α 2macroglobulin and pregnancy zone protein are encoded by two exons, with conserved exon/intron boundaries. A genetic polymorphism showing either a Met or a Val residue as the sixth amino acid of the pregnancy zone protein bait domain was detected with the rare Met allele showing a gene frequency of 0.065.

In this work, the intensity of the CH(A²Δ) chemiluminescence, I(CH*), as well as the concentrations of ground state C2H radicals and O atoms were measured as a function of the reaction time in a variety of helium-diluted C2H2/O/H mixtures in an isothermal flow reactor at temperatures of 290, 410, 520, 590, 675, and 925 K and at a total pressure of 2 Torr. The species concentrations [O] and [C2H] were measured using molecular beam sampling−threshold ionization mass spectrometry (MB-TIMS). At each temperature, the intensity I(CH*) was found to be directly proportional to the [C2H][O] concentration product, over a range of two decades, irrespective of the initial mixture composition or the reaction time. Using the NO + O → NO2* chemiluminescence as a calibration standard, CH* formation rates were derived from the measured I(CH*), and the values of the rate coefficient k2a of the CH*-forming reaction channel C2H + O → CH(A²Δ) + CO (r2a) were thus derived from the slopes of the I(CH*) versus [C2H][O] plots. The results, for 290 K < T < 925 K, can be represented by the Arrhenius expression k2a = 2.4 × 10^-11 exp[−230/T(K)] cm³ molecule^-1 s^-1; the possible systematic error is a factor of 2, due to the uncertainty of the C2H calibration factor. The value at 290 K, 1.1 × 10^-11, is in fair agreement with our recent result obtained in an independent pulse laser photolysis/chemiluminescence experiment. The addition of methane was found to suppress I(CH*) in quantitative agreement with the C2H formation mechanism in C2H2/O/H systems elucidated earlier by us. It is argued that the fast reaction r2a is a major if not the dominant CH* source also in hot hydrocarbon flames.

MSX1 mutations have been reported in four unrelated families with autosomal dominant tooth agenesis. In one family, some individuals also had cleft lip and/or palate. We have identified a novel MSX1 mutation (559 C → T, resulting in Gln187Stop) in three individuals of one family. © 2004 Wiley‐Liss, Inc.

This report describes the prenatal findings in monozygotic twins with Costello syndrome. At 16 weeks one twin had 9 mm of nuchal oedema: coarctation of the aorta was diagnosed after birth. At 22^5/7 weeks relative macrocephaly, mild pyelectasia and moderate polyhydramnios were noted in both twins. In the following 4 weeks the polyhydramnios increased significantly without visualisation of filling of the stomach. Between 27^5/7 and 30^2/7 weeks a total of 9 l amniotic fluid was drained and at 30^4/7 weeks prelabor premature rupture of membranes (PPROM) occurred followed by premature labor and delivery. The neonatal period was complicated by growth retardation, deglutition problems, hypotonia, cardiac and respiratory problems. Both twins died on Day 57 because of respiratory insufficiency. Copyright © 2002 John Wiley & Sons, Ltd.

This report describes the prenatal findings in monozygotic twins with Costello syndrome. At 16 weeks one twin had 9 mm of nuchal oedema: coarctation of the aorta was diagnosed after birth. At 225/7weeks relative macrocephaly, mild pyelectasia and moderate polyhydramnios were noted in both twins. In the following 4 weeks the polyhydramnios increased significantly without visualisation of filling of the stomach. Between 275/7and 302/7weeks a total of 9 l amniotic fluid was drained and at 304/7weeks prelabor premature rupture of membranes (PPROM) occurred followed by premature labor and delivery. The neonatal period was complicated by growth retardation, deglutition problems, hypotonia, cardiac and respiratory problems. Both twins died on Day 57 because of respiratory insufficiency. Copyright © 2002 John Wiley & Sons, Ltd.

We describe a familial mental retardation syndrome in a 30 year old, moderately mentally retarded female and her 59 year old maternal aunt. Both presented the distinct association of (1) a non-progressive neurological syndrome with ataxia and hypotonia, (2) similar craniofacial appearance with a narrow forehead, prominent supraorbital ridges and tendency to synophrys, deeply set eyes with short, upward slanting palpebral fissures, short philtrum, and large mouth, (3) hypergonadotrophic hypogonadism, and (4) retinal dystrophy with onset in early adulthood.

We report on a family with asplenia syndrome in one and total anomalous pulmonary venous connection (TAPVC) in the other sib. Both conditions are rare, may have a genetic cause and belong to a spectrum of laterality disorders. This suggests that both asplenia syndrome and TAPVC in this family are the clinical expression of a single genetic disorder.

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