| 1. |
- Jameel, Muhammad, et al.
(författare)
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A novel AP4M1 mutation in autosomal recessive cerebral palsy syndrome and clinical expansion of AP-4 deficiency
- 2014
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 15, s. 133-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Cerebral palsy (CP) is a heterogeneous neurodevelopmental disorder associated with intellectual disability in one-third of cases. Recent findings support Mendelian inheritance in subgroups of patients with the disease. The purpose of this study was to identify a novel genetic cause of paraplegic CP with intellectual disability in a consanguineous Pakistani family.METHODS:We performed whole-exome sequencing (WES) in two brothers with CP and intellectual disability. Analysis of AP4M1 mRNA was performed using quantitative real-time PCR on total RNA from cultured fibroblasts. The brothers were investigated clinically and by MRI.RESULTS:We identified a novel homozygous AP4M1 mutation c.194_195delAT, p.Y65Ffs*50 in the affected brothers. Quantitative RT-PCR analysis showed markedly reduced AP4M1 mRNA levels suggesting partial non-sense mediated mRNA decay. Several clinical and MRI features were consistent with AP-4 complex deficiency. However, in contrast to previously reported cases with AP4M1 mutations our patients show an aggressive behavior and a relatively late onset of disease.CONCLUSION:This study shows an AP4M1 mutation associated with aggressive behavior in addition to mild dysmorphic features, intellectual disability, spastic paraparesis and reduced head circumference. Our findings expand the clinical spectrum associated with AP-4 complex deficiency and the study illustrates the importance of MRI and WES in the diagnosis of patients with CP and intellectual disability.
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| 2. |
- Khan, Tahir Naeem, et al.
(författare)
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Novel missense mutation in the RSPO4 gene in congenital hyponychia and evidence for a polymorphic initiation codon (p.M1l)
- 2012
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 13, s. 120-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Anonychia/hyponychia congenita is a rare autosomal recessive developmental disorder characterized by the absence (anonychia) or hypoplasia (hyponuchia) of finger- and/or toenails frequently caused by mutations in the R-spondin 4 (RSPO4) gene. Methods: Three hypo/anonychia consanguineous Pakistani families were ascertained and genotyped using microsatellite markers spanning the RSPO4 locus on chromosome 20p13. Mutation screening of the RSPO4 gene was carried out by direct sequencing of the entire coding region and all intron-exon boundaries. Results: Mutations in the RSPO4 gene were identified in all families including a novel missense mutation c.178C>T (p.R60W) and two recurrent variants c.353G>A (p.C118Y) and c.3G>A (p.M1l). The c.3G>A variant was identified in unaffected family members and a control sample in a homozygous state. Conclusions: This study raises to 17 the number of known RSPO4 mutations and further expands the molecular repertoire causing hypo/anonychia. The c.353G>A emerges as a recurrent change with a possible founder effect in the Pakistani population. Our findings suggest that c.3G>A is not sufficient to cause the disorder and could be considered a polymorphism.
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| 3. |
- Raykova, Doroteya, et al.
(författare)
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Autosomal Recessive Transmission of a Rare KRT74 Variant Causes Hair and Nail Ectodermal Dysplasia : Allelism with Dominant Woolly Hair/Hypotrichosis
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4, s. e93607-
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Tidskriftsartikel (refereegranskat)abstract
- Pure hair and nail ectodermal dysplasia (PHNED) comprises a heterogeneous group of rare heritable disorders characterized by brittle hair, hypotrichosis, onychodystrophy and micronychia. Autosomal recessive (AR) PHNED has previously been associated with mutations in either KRT85 or HOXC13 on chromosome 12p11.1-q14.3. We investigated a consanguineous Pakistani family with AR PHNED linked to the keratin gene cluster on 12p11.1 but without detectable mutations in KRT85 and HOXC13. Whole exome sequencing of affected individuals revealed homozygosity for a rare c.821T> C variant (p.Phe274Ser) in the KRT74 gene that segregates AR PHNED in the family. The transition alters the highly conserved Phe274 residue in the coil 1B domain required for long-range dimerization of keratins, suggesting that the mutation compromises the stability of intermediate filaments. Immunohistochemical (IHC) analyses confirmed a strong keratin-74 expression in the nail matrix, the nail bed and the hyponychium of mouse distal digits, as well as in normal human hair follicles. Furthermore, hair follicles and epidermis of an affected family member stained negative for Keratin-74 suggesting a loss of function mechanism mediated by the Phe274Ser substitution. Our observations show for the first time that homozygosity for a KRT74 missense variant may be associated with AR PHNED. Heterozygous KRT74 mutations have previously been associated with autosomal dominant woolly hair/ hypotrichosis simplex (ADWH). Thus, our findings expand the phenotypic spectrum associated with KRT74 mutations and imply that a subtype of AR PHNED is allelic with ADWH.
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| 4. |
- Fulati, Alimujiang, 1981-, et al.
(författare)
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An intracellular glucose biosensor based on nanoflake ZnO
- 2010
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Ingår i: Sensors and actuators. B, Chemical. - : Elsevier. - 0925-4005 .- 1873-3077. ; 150:2, s. 673-680
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this study, an improved potentiometric intracellular glucose biosensor was fabricated with immobilization of glucose oxidase on a ZnO nanoporous material. The ZnO nanoporous material with a wall thickness around 200 nm was grown on the tip of a borosilicate glass capillary and used as a selective intracellular glucose sensor for the measurement of glucose concentrations in human adipocytes and frog oocytes. The results showed a fast response within 4 s and a linear glucosedependent electrochemical response over a wide range of glucose concentration (500 nM-10 mM). The measurements of intracellular glucose concentrations with our biosensor were consistent with the values of intracellular glucose concentrations reported in the literature. The sensor also demonstrated its capability by detecting an increase in the intracellular glucose concentration induced by insulin. We found that the ZnO nanoporous material provides sensitivity as high as 1.8 times higher than that obtained using ZnO nanorods under the same conditions. Moreover, the fabrication method in our experiment is simple and the excellent performance of the developed nanosensor in sensitivity, stability, selectivity, reproducibility and anti-interference was achieved. All these advantageous features of this intracellular glucose biosensor based on functionalised ZnO nanoporous material compared to ZnO nanorods demonstrate a promising way of enhancing glucose biosensor performance to measure reliable intracellular glucose concentrations within single living cells.
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| 5. |
- Khan, Tahir Naeem, et al.
(författare)
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Evidence for autosomal recessive inheritance in SPG3A caused by homozygosity for a novel ATL1 missense mutation
- 2014
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 22:10, s. 1180-1184
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary spastic paraplegias (HSPs) comprise a heterogeneous group of disorders characterized by progressive spasticity and weakness of the lower limbs. Autosomal dominant and 'pure' forms of HSP account for similar to 80% of cases in Western societies of whom 10% carry atlastin-1 (ATL1) gene mutations. We report on a large consanguineous family segregating six members with early onset HSP. The pedigree was compatible with both autosomal dominant and autosomal recessive inheritance. Whole-exome sequencing and segregation analysis revealed a homozygous novel missense variant c.353G>A, p.(Arg118Gln) in ATL1 in all six affected family members. Seven heterozygous carriers, five females and two males, showed no clinical signs of HSP with the exception of sub-clinically reduced vibration sensation in one adult female. Our combined findings show that homozygosity for the ATL1 missense variant remains the only plausible cause of HSP, whereas heterozygous carriers are asymptomatic. This apparent autosomal recessive inheritance adds to the clinical complexity of spastic paraplegia 3A and calls for caution using directed genetic screening in HSP.
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| 6. |
- Klar, Joakim, et al.
(författare)
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Abolished InsP3R2 function inhibits sweat secretion in both humans and mice
- 2014
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 124:11, s. 4773-4780
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Tidskriftsartikel (refereegranskat)abstract
- There are 3 major sweat-producing glands present in skin; eccrine, apocrine, and apoeccrine glands. Due to the high rate of secretion, eccrine sweating is a vital regulator of body temperature in response to thermal stress in humans; therefore, an inability to sweat (anhidrosis) results in heat intolerance that may cause impaired consciousness and death. Here, we have reported 5 members of a consanguineous family with generalized, isolated anhidrosis, but morphologically normal eccrine sweat glands. Whole-genome analysis identified the presence of a homozygous missense mutation in ITPR2, which encodes the type 2 inositol 1,4,5-trisphosphate receptor (InsP3R2), that was present in all affected family members. We determined that the mutation is localized within the pore forming region of InsP3R2 and abrogates Ca2+ release from the endoplasmic reticulum, which suggests that intracellular Ca2+ release by InsP3R2 in clear cells of the sweat glands is important for eccrine sweat production. Itpr2–/– mice exhibited a marked reduction in sweat secretion, and evaluation of sweat glands from Itpr2–/– animals revealed a decrease in Ca2+ response compared with controls. Together, our data indicate that loss of InsP3R2-mediated Ca2+ release causes isolated anhidrosis in humans and suggest that specific InsP3R inhibitors have the potential to reduce sweat production in hyperhidrosis.
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| 7. |
- Nawaz, Sadia, et al.
(författare)
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Non-bullous congentital ichthyosiform erythroderma associated with homozygosity for a novel missense mutation in an ATP binding domain of ABCA12
- 2012
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Ingår i: EJD. European journal of dermatology. - : John Libbey Eurotext. - 1167-1122 .- 1952-4013. ; 22:2, s. 178-181
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Tidskriftsartikel (refereegranskat)abstract
- A Mutations in the gene encoding the ABCA12 protein are associated with different subtypes of autosomal recessive congenital ichthyosis (ARCI), including Harlequin ichthyosis (HI), lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE). Disruption of ABCA12 lead to perturbed lipid transport in lamellar granules and a defective intercellular lipid layer of the stratum corneum. We have identified a large consanguineous Pakistani family affected by NCIE. Autozygosity mapping showed that affected individuals are homozygous for the ABCA12 gene region. Subsequent mutation screening revealed a homozygous c.4676G>T transition in all five affected family members. The mutation results in a novel p.G1559V substitution within the first nucleotide binding domain of ABCA12. The combined results support that an ABCA12 missense mutation, despite its location in a functional domain, may be associated with a mild ichthyosis phenotype. Furthermore, our findings increase the mutational spectrum in ABCA12 associated with ARCI of diagnostic and prognostic importance.
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| 8. |
- Ul Hassan Alvi, Naveed, et al.
(författare)
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Junction temperature in n-ZnO nanorods/(p-4H-SiC, p-GaN, and p-Si) heterojunction light emitting diodes
- 2010
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Ingår i: Solid-State Electronics. - : Elsevier Science B.V., Amsterdam.. - 0038-1101 .- 1879-2405. ; 54:5, s. 536-540
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Tidskriftsartikel (refereegranskat)abstract
- The junction temperature of n-ZnO nanorods/(p-4H-SiC, p-GaN, and p-Si) heterojunction light emitting diodes (LEDs) at built-in potential was modeled and experiments were performed at various temperatures (15-65 degrees C) to validate the model. As the LEDs operate near the built-in potential thats why it is interesting to investigate the temperature coefficient of forward voltage near the built-in potential (similar to V-o). The model and experimental values of the temperature coefficient of forward voltage near the built-in potential (similar to V-o) were compared. We measured the experimental temperature coefficient of the series resistance. By including the temperature coefficient of the series resistance in the model, the theoretical and experimental values become very close to each other. It was found that the series resistance has the main contribution in the junction temperature of our devices. We also measured the junction temperature above the built-in potential and found that the model deviates at higher forward voltage. From this observation we concluded that the model is applicable for low power devices, operated near the built-in potential.
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| 9. |
- Willander, Magnus, et al.
(författare)
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Intrinsic White Light Emission from Zinc Oxide Nanorods Heterojunctions on Large Area Substrates
- 2011
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Ingår i: Proceedings of SPIE Volume 7940. - Bellingham, Washington, USA : SPIE - International Society for Optical Engineering. - 9780819484772
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Zinc oxide (ZnO) and especially in the nanostructure form is currently being intensively investigated world wide for the possibility of developing different new photonic devices. We will here present our recent findings on the controlled low temperature chemical growth of ZnO nanorods (NRs) on different large area substrates. Many different heterojunctions of ZnO NRs and p-substrates including those of crystalline e. g. p-GaN, p-SiC or amorphous nature e. g. p-polymer coated plastic and p-polymer coated paper will be shown. Moreover, the effect of the p-electrode of these heterojunctions on tuning the emitted wavelength and changing the light quality will be discussed. An example using ZnO NR/p-GaN will be shown and the electrical and electro-optical characteristics will be analyzed. For these heterojunctions the effect of post growth annealing and its effect on the electroluminescence (EL) spectrum will be shown. Finally, intrinsic white light emitting diodes based on ZnO NRs on foldable and disposable amorphous substrates (plastic and paper) will also be presented.
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| 10. |
- Yaqoob, Muhammad Atif, et al.
(författare)
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On the Performance of Random Antenna Arrays for Direction of Arrival Estimation
- 2014
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Ingår i: [Host publication title missing]. - 2164-7038. ; , s. 193-199
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Konferensbidrag (refereegranskat)abstract
- A single antenna based virtual antenna array at the receiver can be used to find direction of different incoming radio signals impinging at the receiver. In this paper, we investigate the performance of random 3D virtual antenna arrays for DoA estimation. We have computed a Cramer-Rao Lower Bound (CRLB) for DoA estimation if the true antenna positions are not known, but these are estimated with an uncertainty. Position displacement is estimated with an extended Kalman filter (EKF) by using simulated data samples of acceleration and rotation rate which are corrupted by stochastic errors, such as, white Gaussian noise and bias drift. Furthermore, the effect of position estimation error on the DoA estimation performance is evaluated using the CRLB. The results show that the number of useful elements in the antenna array is limited, because the standard deviation of the position estimation error grows over time.
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