A deletion mutation in the βA1/A3 crystallin gene (CRYBA1/A3) is associated with autosomal dominant congenital nuclear cataract in a Chinese family

Congenital cataracts are an important cause of blindness worldwide. In a family of Chinese descent, a dominant congenital nuclear cataract locus was mapped to chromosome 17q11.1-12. The maximum LOD score, 2.49, at recombination fraction 0, was obtained for marker D17S1294. The results of both linkage and haplotype analyses defined a disease-gene to an 11.78-cM region harboring the gene coding for A1/A3 crystallin (CRYBA1/A3). Mutation analysis of the CRYBA1/A3 gene identified a 3-bp deletion in exon 4, which cosegregated with the disease risk in this family and was not observed in 100 normal chromosomes. This mutation resulted in the deletion of a highly conserved glycine at codon 91 (G91) and could be associated with an incorrect folding of A1/A3 crystallin. It highlights the physiological importance of crystallin and supports the role of CRYBA1/A3 in human cataracts formation.Y. Qi and H. Jia contributed equally to this work     

Localization of a gene for autosomal dominant osteopetrosis (Albers-Sch?nberg disease) to chromosome 1p21.

Albers-Schönberg disease, the classical form of osteopetrosis, is an autosomal dominant condition with generalized increased skeletal density due to reduced bone resorption. Characteristic radiological findings are generalized osteosclerosis, with, most typically, end-plate sandwichlike thickening of the vertebrae (Rugger-Jersey spine) and the bone-within-bone (endobones) phenomenon. We studied an extended kindred with Albers-Schönberg disease and found linkage with several markers from chromosome 1p21. The Albers-Schönberg gene is located in a candidate region of approximately 8.5 cM flanked by markers D1S486 and D1S2792. A maximum LOD score (Z(max)) of 4.09 was obtained in multipoint analysis at loci D1S239/D1S248. Possible linkage of osteopetrosis to this chromosomal region was analyzed because the CSF-1 gene, which is mutated in the op/op mouse model for osteopetrosis, is located in 1p21. However, SSCP and mutation analysis in patients did not reveal any abnormality, which excludes the CSF-1 gene as the disease-causing gene. This was confirmed by refined physical mapping of the CSF-1 gene outside the candidate region for the Albers-Schönberg gene. The identification of the molecular defect underlying Albers-Schönberg disease will therefore be dependent on the isolation of other genes from an 8.5-cM candidate region on chromosome 1p21.     

Identification of a novel CCM2 gene mutation in an Italian family with multiple cerebral cavernous malformations and epilepsy: A causative mutation?

Cerebral cavernous malformations (CCMs; OMIM 116860) are vascular anomalies mostly located in the central nervous system (CNS) and occasionally within the skin and retina.     

Segregation of a mutation in CNGB1 encoding the β-subunit of the rod cGMP-gated channel in a family with autosomal recessive retinitis pigmentosa

Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of retinal diseases leading to blindness. By performing full genome linkage analysis in a consanguineous French family affected with severe autosomal recessive RP, we have excluded linkage to known loci involved in RP and mapped a novel locus to chromosome 16q13-q21 (Zmax=2.83 at theta=0 at the D16S3089 locus). Two candidate genes KIFC3 and CNGB1 mapping to this critical interval have been screened for mutations. The CNGB1 gene, which encodes the beta-subunit of the rod cGMP-gated channel, is mutated in the family presented in this study.     

Changes in the sugarcane metabolome with stem development. Are they related to sucrose accumulation?

Sucrose content increases with internode development down the stem of sugarcane. In an attempt to determine which other changes in metabolites may be linked to sucrose accumulation gas chromatography-mass spectrometry was used to obtain metabolic profiles from methanol/water extracts of four samples of different age down the stem of cultivar Q117. Extracts were derivatized with either N-methyl-N-(trimethylsilyl) trifluoracetamide (TMS) or N-methyl N-(tert-butyldimethylsilyl) trifluoroacetamide (TBS) separately in order to increase the number of metabolites that could be detected. This resulted in the measurement of 121 and 71 metabolites from the TMS and TBS derivatization, respectively. Fifty-five metabolites were identified using commercial and publicly available libraries. Statistical analysis of the metabolite profiles resulted in clustering of tissue types. Particular metabolites were correlated with the level of sucrose accumulation, which as expected increased down the stem. Metabolites, such as tricarboxylic acid cycle intermediates and amino acids, were more abundant in the M2 sample (meristem to internode 2) that was actively growing and decreased in an apparently coordinated developmentally programmed manner in more mature internodes down the stem. However, other metabolites such as trehalose and raffinose showed positive correlations with sucrose concentration. Here we discuss the technique used to measure metabolites in sugarcane and the changes in metabolite abundance down the sugarcane stem.     

A novel missense mutation in the thyroid hormone receptor β gene in a kindred with resistance to thyroid hormone

Direct sequencing of exon 9 of the thyroid hormone receptor (TR) gene in a kindred with resistance to thyroid hormone revealed a substitution of threonine for methionine in codon 313 in one allele resulting from a T to C transition. This is a novel missense mutation that resides in one of the two mutational hot-spot regions of the TR gene suggesting altered triiodothyronine binding to this mutant receptor.     

A novel RAB7 mutation in a Chinese family with Charcot–Marie–Tooth type 2B disease

Charcot–Marie–Tooth type 2B (CMT2B) disease is a hereditary motor and sensory neuropathy subtype characterized by prominent loss of sensation, distal muscle weakness and wasting skin ulcers. Recurrent ulcers often require amputation of lower limbs. To date, only four mutations of the RAB7 gene, which encodes the small GTPase, have been associated with CMT2B. A Chinese family with CMT2B was identified. Direct DNA sequencing performed on the affected individuals in this family revealed a novel mutation (p.Asn161Ile) in RAB7. The mutation is located in a potential mutational hotspot region, implicating the importance of this region for RAB7 protein. This is the first report of RAB7 mutation in Asian population.     

A novel TNNI2 mutation causes Freeman–Sheldon syndrome in a Chinese family with an affected adult with only facial contractures

Distal arthrogryposes (DAs), a clinically and genetically heterogeneous group of disorders characterized by congenital contractures with predominant involvement of the hands and feet, can be classified into at least 12 different forms. These autosomal dominant disorders are of variable expressivity and reduced penetrance. Mutations in sarcomeric protein genes, including troponin I2 (TNNI2), troponin T3 (TNNT3), tropomyosin 2 (TPM2), embryonic myosin heavy chain 3 (MYH3), and myosin binding protein C1 (MYBPC1), have been identified in distal arthrogryposis type 1 (DA1, MIM 108120), type 2B (DA2B, MIM 601680) and type 2A (DA2A)/Freeman–Sheldon syndrome (FSS, MIM 193700). However, mutations causing FSS have only been reported in MYH3. Herein we describe a Chinese DA family whose members meet classical strict criteria for FSS, as well as one member of the family who has isolated facial features consistent with FSS. No disease-causing mutation was found in MYH3. Segregation of microsatellite markers flanking the TNNI2 and TNNT3 genes at 11p15.5 was compatible with linkage. Subsequent sequencing of TNNI2 revealed a novel mutation, c.A493T (p.I165F), located in the C-terminal region, which is critical for proper protein function. This mutation was found to cosegregate with the FSS phenotype in this family, and assessment using SIFT and PolyPhen-2 predicted a damaging effect. To the best of our knowledge, we report the first TNNI2 mutation in classical FSS and describe an atypical adult FSS case with only facial contractures resulting from somatic mosaicism. We infer that DA1, DA2B and FSS represent a phenotypic continuum of the same disorder and provide further genetic evidence for this hypothesis.     

Further evidence of autosomal dominant congenital zonular pulverulent cataracts linked to 13q11 (CZP3) and a novel mutation in connexin 46 (GJA3)

We describe a four-generation family with fully penetrant, autosomal dominant, congenital cataracts (ADCC), presenting with morphologically homogeneous "zonular pulverulent" cataracts (CZP) and typical early-onset phenotype. Linkage analysis was performed with a panel of polymorphic markers mapped to all genomic regions of ADCC susceptibility. Contiguous significant two-point lod scores were generated at autosomal region 13q11-q13 and further linkage and haplotype studies confined the disease locus to 13q11, supporting a previous linkage of CZP (specifically CZP3) to 13q11. Mutations in a gap-junction protein, connexin 46 (alphaa3 subunit or GJA3), have recently been reported as being linked to the 13q11 region. Mutational analysis of connexin 46 in our family revealed a C-->T at position 560 (P187L) of the cDNA sequence creating a novel MnlI restriction site that segregated with affected members of the pedigree. This family represents a second report of CZP3 linkage to 13q and is associated with a novel mutation in the connexin 46 (GJA3) gene.     

Brachydactyly type E in two sibs with increased bone density and mental retardation. A new autosomal recessive syndrome?

Brachydactyly type E in two sibs with increased bone density and mental retardation. A new autosomal recessive syndrome?: We report on two sibs, a boy and a girl, with syndromic brachydactyly type E. Parents were first cousins. Facial dysmorphia was characterized by a flat occiput, a large forehead, hypertelorism, a long triangular nose, an everted lower lip, downslanting palpebral fissures and strabismus. They had marked shortening of the third, fourth and fifth fingers and of the third, fourth, and fifth toes. IQ was 16 in the boy, 63 in the girl. In both sibs ophtalmologic examination showed strabismus, absence of cataract and normal fundus and radiological findings disclosed increased bone density involving the skull, the vertebrae and the corticalis of the long bones. Neither ectopic calcifications, nor exostosic, nor osteomalacia, and nor osteotis fibrosa cystica were present. Investigations revealed that plasma calcium, phosphate, vitamine D, parathyroid hormone (PTH), response to exogenous PTH, and Gs activity were normal as well as renal and thyroid function. Molecular genetic studies failed to identify mutations in the GNAS 1 gene, in the PTH receptor gene and in the HOX D13 gene. Analysis of 2q showed that there was no deletion 2q37. Other known syndromes with brachydactyly type E and mental retardation were excluded. In conclusion we suggest that these two sibs with a combination of brachydactyly, mental retardation and increased bone density have a specific autosomal recessive syndrome.     

Is community persistence related to diversity? A test with prairie species in a long-term experiment

Community persistence, or the ability of a community to maintain species composition and diversity through time, is a component of stability that is important to restoration. We ran a biodiversity–ecosystem functioning experiment for three years, and then stopped weeding it for 5–6 years, which allowed us to test whether increased plant species diversity and dissimilarity in height would lead to increased community persistence in the face of high invasion pressure by non-native species. Our approach was unique in that the experiment varied richness (one or four species) and evenness (three levels plus monocultures of the dominant species) using two separate dissimilarity types (having all tall species or having tall and short species combined) in six spatiotemporal blocks. Persistence was quantified as to how well positive productivity–diversity relationships, proportion of planted native species, and species richness remained unchanged over time. Thus, high persistence values indicate low levels of invasion and local extinction. We found that the positive relationship between diversity measures and productivity persisted after cessation of weeding. The proportion of planted species was 32% higher in mixture than in monoculture plots, indicating that monocultures were more heavily invaded by non-native species. Reduced evenness did not affect persistence measures in plots with dissimilar heights, but measures declined linearly with decreased evenness in plots with all tall species. Our results suggest that (1) persistence–diversity relationships are likely to vary with the traits of species becoming rare and going extinct, and (2) it is important to restore higher species diversity in restoration projects to favor the long-term persistence of planted species.     

The Duffy blood group is linked to the α-spectrin locus in a large pedigree with autosomal dominant inheritance of Charcot-Marie-Tooth disease type 1

Summary The -spectrin locus (SPTA) on chromsome 1 maps to 1q22–q25 and -spectrin specific probes detect restriction fragment length polymorphisms (RFLPs) with the endonucleases MspI and PvuII. The Duffy blood group (FY) has been mapped to the 1p21–q23 region. We found positive linkage between the -spectrin and the Duffy loci with a maximal Lod score of 3.81 at =0.0 using the computer program MLINK. This indicates that both loci are very closely linked and probably localized to 1q22–q23.     

A novel family 9 β-1,3(4)-glucanase from thermoacidophilic Alicyclobacillus sp. A4 with potential applications in the brewing industry

An endo-β-1,3(4)-glucanase gene, Agl9A, was cloned from Alicyclobacillus sp. A4 and expressed in Pichia pastoris. Its deduced amino acid sequence shared the highest identity (48%) with an endo-β-1,4-glucansae from Alicyclobacillus acidocaldarius that belongs to family 9 of the glycoside hydrolases. The purified recombinant Agl9A exhibited relatively wide substrate specificity, including lichenan (109%), barley β-glucan (100%), CMC-Na (15.02%), and laminarin (6.19%). The optimal conditions for Agl9A activity were pH 5.8 and 55°C. The enzyme was stable over a broad pH range (>60% activity retained after 1-h incubation at pH 3.8–11.2) and at 60°C (>70% activity retained after 1-h incubation). Agl9A was highly resistant to various neutral proteases (e.g., trypsin, α-chymotrypsin, and collagenase) and Neutrase 0.8L (Novozymes), a protease widely added to the mash. Under simulated mashing conditions, addition of Agl9A (20 U/ml) or a commercial xylanase (200 U/ml) reduced the filtration rate (26.71% and 20.21%, respectively) and viscosity (6.12% and 4.78%, respectively); furthermore, combined use of Agl9A (10 U/ml) and the xylanase (100 U/ml) even more effectively reduced the filtration rate (31.73%) and viscosity (8.79%). These characteristics indicate that Agl9A is a good candidate to improve glucan degradation in the malting and brewing industry.     

FGFR3 mutation in thanatophoric dysplasia type 1 with bilateral cystic renal dysplasia: coincidence or a new association?

Thanatophoric dysplasia (TD) is a lethal dwarfism condition due to missense mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Examination of TD patients reveals mainly the involvement of the skeletal system and the brain, but also renal and cardiovascular anomalies have been described. We report the prenatal detection of TD type 1 (TD1) associated with bilateral cystic renal dysplasia (CRD) Potter's type II, in which the molecular analysis reveals the typical Arg248Cys substitution in the FGFR3 gene. CRD has not been previously described in TD or other conditions due to FGFR3 mutations, but occurs in Apert syndrome (due to FGFR2 mutations). The possible involvement of renal developmental defect in FGFR3 mutations is discussed.     

How is extinction risk related to population-size variability over time? A family of models for species with repeated extinction and immigration

It is well known that for an isolated population, the probability of extinction is positively related to population size variation: more variation is associated with more extinction. What, then, is the relation of extinction to population size variation for a population embedded in a metapopulation and subjected to repeated extinction and recolonization? In this case, the extinction risk can be measured by the extinction rate, the frequency at which local extinction occurs. Using several population dynamics models with immigration, we find, in general, a negative correlation between extinction and variation. More precisely, with increasing length of the time series, an initially negative regression coefficient first becomes more negative, then becomes less negative, and eventually attains positive values before decreasing again to 0. This pattern holds under substantial variation in values of parameters representing species and environmental properties. It is also rather robust to census interval length and the fraction of missed individuals but fails to hold for high thresholds (population size values below which extinction is deemed to occur) when quasi extinction rather than true extinction is represented. The few departures from the initial negative correlation correspond to populations at risk: low growth rate or frequent catastrophes.     

Orientisargidae fam. n., a new Jurassic family of Archisargoidea (Diptera,Brachycera), with review?of?Archisargidae from China

A pair of fly impressions is described as a new species of a new genus, Orientisargus illecebrosus gen. et sp. n., referred to a new family Orientisargidae fam. n. within Archisargoidea of Brachycera, Diptera. The systematic position of Orientisargidae is discussed. Daohugosargus gen. n. is proposed for Sharasargus eximius KY Zhang et al., 2008. Uranorhagionidae is a junior synonym for Archisargidae. Meanwhile, Mostovskisarginae is a junior synonym for Uranorhagionidae. Mostovskisargus JF Zhang, 2010 and Strenorhagio KY Zhang et al., 2010 are synonymized with Uranorhagio KY Zhang et al., 2010. Uranorhagio includes three species: Uranorhagio asymmetricus (KY Zhang et al., 2010), comb. n., Uranorhagio daohugouensis KY Zhang et al., 2010 and Uranorhagio deviatus (KY Zhang et al., 2010), comb. n. Strenorhagio grimaldi KY Zhang et al., 2010 is synonymous with Uranorhagio deviatus. Mostovskisargus portentosus JF Zhang, 2010, Mostovskisargus signatus JF Zhang, 2010 and Strenorhagio conjugovenius KY Zhang et al., 2010 are synonymous with Uranorhagio asymmetricus. Brevisolva KY Zhang et al., 2010 is a junior synonym for Mesosolva Hong, 1983. A new specific name, Mesosolva zhangae nom. n., is proposed for Brevisolva daohugouensis KY Zhang et al., 2010. Mesosolva jurassica KY Zhang et al., 2010 should be synonymized under Mostovskisargus sinensis KY Zhang et al., 2010. Sinallomyia nom. n. is proposed for Allomyia Ren, 1998. The systematic positions for Helempis eucalla Ren, 1998, Helempis yixianensis Ren, 1998, Pauromyia oresbia Ren, 1998 and Sinallomyia ruderalis (Ren, 1998) are reassessed. These taxa belong to Archisargidae rather than to Tabanidae, Rhagionidae and Protempididae, respectively.     

Alona brandorffi sp. n. (Crustacea: Anomopoda: Chydoridae) – a new species from Brazil, related to A. verrucosa Sars, 1901

Alona brandorffi sp. n, related to A. verrucosa Sars, 1901 is described from Boa Vista, Brazil. Parthenogenetic females and males of A. brandorffi were studied. Examination of trunk limbs of A. brandorffi reveals several unusual modifications in structure, unique for the genus, such as very short setae on endites 2 and 3 of limb I, peculiar IDL setae, limb II with scrapers 7–8 with reduced distal part and only six, instead of seven setae in the filter plate, limb IV with only three, instead of four, setae on the inner lobe. The relationships and place of A. brandorffi within the genus Alona are discussed.