| 1. |
- Fröjmark, Anne-Sophie, et al.
(författare)
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Mutations in frizzled 6 cause isolated autosomal-recessive nail dysplasia
- 2011
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 88:6, s. 852-860
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Tidskriftsartikel (refereegranskat)abstract
- Inherited and isolated nail malformations are rare and heterogeneous conditions. We identified two consanguineous pedigrees in which some family members were affected by isolated nail dysplasia that suggested an autosomal-recessive inheritance pattern and was characterized by claw-shaped nails, onychauxis, and onycholysis. Genome-wide SNP array analysis of affected individuals from both families showed an overlapping and homozygous region of 800 kb on the long arm of chromosome 8. The candidate region spans eight genes, and DNA sequence analysis revealed homozygous nonsense and missense mutations in FZD(6), the gene encoding Frizzled 6. FZD(6) belongs to a family of highly conserved membrane-bound WNT receptors involved in developmental processes and differentiation through several signaling pathways. We expressed the FZD(6) missense mutation and observed a quantitative shift in subcellular distribution from the plasma membrane to the lysosomes, where the receptor is inaccessible for signaling and presumably degraded. Analysis of human fibroblasts homozygous for the nonsense mutation showed an aberrant response to both WNT-3A and WNT-5A stimulation; this response was consistent with an effect on both canonical and noncanonical WNT-FZD signaling. A detailed analysis of the Fzd(6)(-/-) mice, previously shown to have an altered hair pattern, showed malformed claws predominantly of the hind limbs. Furthermore, a transient Fdz6 mRNA expression was observed in the epidermis of the digital tips at embryonic day 16.5 during early claw morphogenesis. Thus, our combined results show that FZD6 mutations can result in severe defects in nail and claw formation through reduced or abolished membranous FZD(6) levels and several nonfunctional WNT-FZD pathways.
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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. |
- 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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| 4. |
- Nawaz, Saima, et al.
(författare)
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Polyaniline inside the pores of high surface area mesoporous silicon as composite electrode material for supercapacitors
- 2022
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Ingår i: RSC Advances. - : ROYAL SOC CHEMISTRY. - 2046-2069. ; 12:27, s. 17228-17236
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Tidskriftsartikel (refereegranskat)abstract
- Mesoporous silicon (mSi) obtained by the magnesiothermic reduction of mesoporous silica was used to deposit polyaniline (PANI) in its pores, the composite was tested for its charge storage application for high performance supercapacitor electrodes. The mesoporous silica as confirmed by Small Angle X-ray Scattering (SAXS) has a Brunauer-Emmett-Teller (BET) surface area of 724 m(2)g(-1) and mean pore size of 5 nm. After magnesiothermic reduction to mSi, the BET surface area is reduced to 348 m(2)g(-1) but the mesoporousity is retained with a mean pore size of 10 nm. The BET surface area of mesoporous silicon is among the highest for porous silicon prepared/reduced from silica. In situ polymerization of PANI inside the pores of mSi was achieved by controlling the polymerization conditions. As a supercapacitor electrode, the mSi-PANI composite exhibits better charge storage performance as compared to pure PANI and mesoporous silica-PANI composite electrodes. Enhanced electrochemical performance of the mSi-PANI composite is attributed to the high surface mesoporous morphology of mSi with a network structure containing abundant mesopores enwrapped by an electrochemically permeable polyaniline matrix.
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| 5. |
- Nawaz, Sadia, et al.
(författare)
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Report of a recurrent mutation in ARS (component B) gene with severe Mal de Meleda in a large consanguineous Pakistani family
- 2011
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Ingår i: Pakistan journal of medical sciences print. - 1682-024X .- 1681-715X. ; 27:3, s. 686-689
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To characterize the disease causing mutation in a large consanguineous Pakistani family with severe Mat de Meleda (MDM) or keratosis palmoplantaris transgrediens, a rare autosomal recessive skin disorder. Methodology: Single nucleotide polymorphism (SNPs) genotyping was performed using the Gene Chip Mapping 250K array (Affymetrix). Homozygosity mapping and sorting of genomic regions were performed with dedicated software called AutoSNPa. Selected regions were further investigated by genotyping with microsatellite markers derived from known and novel pOlymorphic repeats. Two-point LOD score calculation was performed by using the MLINK of Fast link computer package. All three coding exons of ARS (component B) gene were amplified by PCR and sequenced. Conclusion: Sequencing of all the coding exons of ARS (component B) gene in the affected individuals revealed a recurrent missense mutation in exon 3 at base pair 256 from Guanine to Alanine (256G>A) and as a result the amino acid Glycine is replaced by Arginine at position 86 (G86R). This finding will facilitate control of affected MDM births in the Pakistani families.
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| 6. |
- Nawaz, Sadia, et al.
(författare)
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WNT10A missense mutation associated with a complete odonto-onycho-dermal dysplasia syndrome
- 2009
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 17:12, s. 1600-1605
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Tidskriftsartikel (refereegranskat)abstract
- Wnt signalling is one of a few pathways that are crucial for controlling genetic programs during embryonic development as well as in adult tissues. WNT10A is expressed in the skin and epidermis and it has shown to be critical for the development of ectodermal appendages. A nonsense mutation in WNT10A was recently identified in odonto-onycho-dermal dysplasia (OODD; MIM 257980), a rare syndrome characterised by severe hypodontia, nail dystrophy, smooth tongue, dry skin, keratoderma and hyperhydrosis of palms and soles. We identified a large consanguineous Pakistani pedigree comprising six individuals affected by a complete OODD syndrome. Autozygosity mapping using SNP array analysis showed that the affected individuals are homozygous for the WNT10A gene region. Subsequent mutation screening showed a homozygous c.392C>T transition in exon 3 of WNT10A, which predicts a p.A131V substitution in a conserved alpha-helix domain. We report here on the first inherited missense mutation in WNT10A with associated ectodermal features.
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| 7. |
- Rasool, Mahmood, et al.
(författare)
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Autosomal recessive pure hair and nail ectodermal dysplasia linked to chromosome 12p11.1-q14.3 without KRTHB5 gene mutation
- 2010
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Ingår i: EJD. European journal of dermatology. - : John Libbey Eurotext. - 1167-1122 .- 1952-4013. ; 20:4, s. 443-446
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Tidskriftsartikel (refereegranskat)abstract
- Hair-nail ectodermal dysplasia (HNED; OMIM 602032) constitutes a rare subgroup of ectodermal dysplasias characterised by onychodystrophy, hypotrichosis and brittle hair. We identified a large consanguineous Pakistani family with four siblings affected by a congenital autosomal recessive form of the disease. Based on previous genetic findings in HNED we performed linkage analysis in the family using chromosome 12 markers. A genetic linkage analysis revealed a lod score of 2.92 ( = 0.0) at locus D12S368, indicating the disease gene to be located on chromosome 12. Candidate genes on chromosome 12, including the KRTHB5 gene and four additional keratin II genes, were sequenced in affected family members. Sequence analysis of the coding regions of keratin KRTHB5 gene, previously associated with a distinct clinical form of hair-nail dysplasia, revealed normal coding regions. Our study confirms linkage of a variant clinical form of hair-nail ectodermal dysplasia to chromosome 12 without any mutation in the coding sequences of the KRTHB5 gene. The results suggest this family to have either a non-coding mutation in the KRTHB5 gene, or a mutation in a yet unknown gene within the linked region on chromosome 12.
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| 8. |
- Saqlain, Muhammad, et al.
(författare)
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Risk variants of obesity associated genes demonstrate BMI raising effect in a large cohort.
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:9
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is highly polygenic disease where several genetic variants have been reportedly associated with obesity in different ethnicities of the world. In the current study, we identified the obesity risk or protective association and BMI raising effect of the minor allele of adiponectin, C1Q and collagen domain containing (ADIPOQ), cholesteryl ester transfer protein (CEPT), FTO alpha-ketoglutarate dependent dioxygenase (FTO), leptin (LEP), and leptin receptor (LEPR) genes in a large cohort stratified into four BMI-based body weight categories i.e., normal weight, lean, over-weight, and obese. Based on selected candidate genetic markers, the genotyping of all study subjects was performed by PCR assays, and genotypes and allele frequencies were calculated. The minor allele frequencies (MAFs) of all genetic markers were computed for total and BMI-based body weight categories and compared with MAFs of global and South Asian (SAS) populations. Genetic associations of variants with obesity risk were calculated and BMI raising effect per copy of the minor allele were estimated. The genetic variants with higher MAFs in obese BMI group were; rs2241766 (G = 0.43), rs17817449 (G = 0.54), rs9939609 (A = 0.51), rs1421085 (C = 0.53), rs1558902 (A = 0.63), and rs1137101 (G = 0.64) respectively. All these variants were significantly associated with obesity (OR = 1.03-4.42) and showed a high BMI raising effect (β = 0.239-0.31 Kg/m2) per copy of the risk allele. In contrast, the MAFs of three variants were higher in lean-normal BMI groups; rs3764261 A = 0.38, rs9941349 T = 0.43, and rs7799039 G = 0.40-0.43). These variants showed obesity protective associations (OR = 0.68-0.76), and a BMI lowering effect per copy of the protective allele (β = -0.103-0.155 Kg/m2). The rs3764261 variant also showed significant and positive association with lean body mass (OR = 2.38, CI = 1.30-4.34). Overall, we report six genetic variants of ADIPOQ, FTO and LEPR genes as obesity-risk markers and a CETP gene variant as lean mass/obesity protective marker in studied Pakistani cohort.
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