Noor Muhammad

Genetic studies of autosomal recessive primary microcephaly in 33 Pakistani families: novel sequence variants in ASPM gene

Human autosomal recessive primary microcephaly (MCPH) is a rare genetic disorder in which affected individuals are born with reduced brain size. MCPH is genetically heterogeneous, with six loci and four genes reported to date. Mutations in the ASPM gene at the MCPH5 locus appear to be the most common cause of MCPH. For this study, 33 Pakistani families with primary microcephaly were enrolled. Genotyping using microsatellite markers linked to the six known MCPH loci showed the linkage of 18 families to the MCPH5 locus, two to the MCPH2 locus, two to the MCPH4 locus, and one to the MCPH6 locus. The remaining ten families were not linked to any of the known loci. Families linked to the MCPH5 locus were further subjected to screening of the ASPM gene with direct DNA sequencing. Two previously reported variants, 3978G>A (W1326X) and 9557C>G (S3186X), were observed in five Pakistani families. Four novel nonsynonymous sequence variants, 9118insCATT, 9238A>T (L3080X), 9539A>C (Q3180P), and 1260delTCAAGTC, were found to segregate within four families, but were not observed in 200 Pakistani control chromosomes. One of the variants, 9539A>C (Q3180P), occurred in the IQ 79 domain, but its functional significance awaits definition.

Novel mutations in natriuretic peptide receptor-2 gene underlie acromesomelic dysplasia, type maroteaux

BackgroundNatriuretic peptides (NPs) are peptide hormones that exert their biological actions by binding to three types of cell surface natriuretic peptide receptors (NPRs). The receptor NPR-B binding C-type natriuretic peptide (CNP) acts locally as a paracrine and/or autocrine regulator in a wide variety of tissues. Mutations in the gene NPR2 have been shown to cause acromesomelic dysplasia-type Maroteaux (AMDM), an autosomal recessive skeletal disproportionate dwarfism disorder in humans.MethodsIn the study, presented here, genotyping of six consanguineous families of Pakistani origin with AMDM was carried out using polymorphic microsatellite markers, which are closely linked to the gene NPR2 on chromosome 9p21-p12. To screen for mutations in the gene NPR2, all of its coding exons and splice junction sites were PCR amplified from genomic DNA of affected and unaffected individuals of the families and sequenced.ResultsSequence analysis of the gene NPR2 identified a novel missence mutation (p.T907M) in five families, and a splice donor site mutation c.2986 + 2 T > G in the other family.ConclusionWe have described two novel mutations in the gene NPR2. The presence of the same mutation (p.T907M) and haplotype in five families (A, B, C, D, E) is suggestive of a founder effect.

Chlorophyll derivatives can be an efficient weapon in the fight against dengue.

Dengue, a mosquito-borne viral infection, is one of the major public health concerns in the tropical and subtropical regions of the world. Approximately, 2.5 billion people across the world are at risk from dengue and 50 to 100 million new infections of dengue occur annually. There is yet no vaccine or medicine available against dengue, and treatment remains only supportive. Targeting its vector by a combination of biological and chemical approaches and management of breeding sites are currently the only existing approaches to control or eliminate dengue. Chlorophyll derivatives like chlorophyllin and pheophorbide have been reported as effective natural photosensitizers against larvae of several insects including flies. Chlorophyll derivatives were also reported effective against larval stages of freshwater snails as well as against certain parasites of fish. This article briefly discusses the possible application of chlorophyll derivatives in controlling dengue vectors and hence the disease itself. Chlorophyll derivatives can prove to be a good contributor in an integrated approach against dengue.

Digenic inheritance of an autosomal recessive hypotrichosis in two consanguineous pedigrees

Basit S, Wali A, Aziz A, Muhammad N, Jelani M, Ahmad W. Digenic inheritance of an autosomal recessive hypotrichosis in two consanguineous pedigrees.

Novel homozygous mutations in the WNT10B gene underlying autosomal recessive split hand/foot malformation in three consanguineous families.

Split-hand/split-foot malformation (SHFM), representing variable degree of median clefts of hands and feet, is a genetically heterogeneous group of limb malformations with seven loci mapped on different human chromosomes. However, only 3 genes (TP63, WNT10B, DLX5) for the seven loci have been identified. The study, presented here, described three consanguineous Pakistani families segregating SHFM in autosomal recessive manner. Linkage in the families was searched by genotyping microsatellite markers and mutation screening of candidate gene was performed by Sanger DNA sequencing. Clinical features of affected members of these families exhibited SHFM phenotype with involvement of hands and feet. Genotyping using microsatellite markers mapped the families to WNT10B gene at SHFM6 on chromosome 12q13.11-q13. Subsequently, sequence analysis of WNT10B gene revealed a novel 4-bp deletion mutation (c.1165_1168delAAGT) in one family and 7-bp duplication (c.300_306dupAGGGCGG) in two other families. Structure-based analysis showed a significant conformational shift in the active binding site of mutated WNT10B (p.Lys388Glufs*36), influencing binding with Fzd8. The mutations identified in the WNT10B gene extend the body of evidence implicating it in the pathogenesis of SHFM.

A novel missense mutation in the gene FZD6 underlies autosomal recessive nail dysplasia

Background  Inherited isolated nail anomaly manifesting with onychauxis and onycholysis is a rare condition, caused by mutations in the gene FZD6, encoding membrane‐bound Wnt receptor protein.

Chlorpyrifos and lambda cyhalothrin-induced oxidative stress in human erythrocytes: In vitro studies.

Pesticides are one of the most potentially harmful chemicals introduced into the environment, and their adverse impacts on non-target organisms can be significant. The present study was conducted to shed light on effects of locally used insecticides chlorpyrifos (CPF) and lambda cyhalothrin (LCT) on oxidative stress biomarkers in human erythrocytes. The activity of catalase (CAT), superoxide dismutase (SOD), and protein contents as well as the levels of malondialdehyde (MDA) and osmotic fragility (OF) were measured in human erythrocytes exposed to CPF at concentrations of 0, 100, 500, 1000, and 2000 ppm and LCT at concentrations of 0, 100, 300, 600, and 800 ppm for 1 h and 3 h at 37°C. MDA levels and OF of erythrocytes were significantly higher in erythrocytes incubated with CPF and LCT at increasing concentrations of both insecticides and increased incubation time. However, erythrocyte CAT and SOD activities were decreased at all concentrations of CPF and LCT tested. Protein oxidation products were decreased at lower doses of CPF (100 and 500 ppm); at higher doses (1000 and 2000 ppm), total protein content was increased compared with control. In contrast LCT was associated with decreased in protein contents at all the concentrations. These results clearly demonstrated that CPF and LCT can induce oxidative stress in human erythrocytes (in vitro).

Genetics of human isolated hereditary nail disorders

Human hereditary nail disorders constitute a rare and heterogeneous group of ectodermal dysplasias. They occur as isolated and/or syndromic ectodermal conditions where other ectodermal appendages are also involved, and can occur associated with skeletal dysplasia. ‘Nail disorder, nonsyndromic congenital’ (OMIM; Online Mendelian Inheritance in Man) is subclassified into 10 different types. The underlying genes identified thus far are expressed in the nail bed and play important roles in nail development and morphogenesis. Here, we review the current literature on nail disorders and present a coherent review on the genetics of nail disorders. This review will pave the way to identifying putative genes and pathways involved in nail development and morphogenesis.

Genetics of human isolated acromesomelic dysplasia.

Acromesomelic dysplasia is a type of skeletal malformation affecting distal and middle segments of the extremities. It occurs in both isolated (non-syndromic) and syndromic forms. In later case, it shows association with cardiac, respiratory, neurological and genital abnormalities. Acromesomelic dysplasia segregates in autosomal recessive mode. Mutations in three genes (GDF5, NPR2, BMPR1B) have been reported to cause different forms of acromesomelic dysplasia. In the present review, we have discussed clinical spectrum, genetics and signalopathies of isolated acromesomelic dysplasias.

Analysis of ferrite nanoparticles in the flow of ferromagnetic nanofluid

Theoretical analysis has been carried out to establish the heat transport phenomenon of six different ferromagnetic MnZnFe2O4—C2H6O2 (manganese zinc ferrite-ethylene glycol), NiZnFe2O4—C2H6O2 (Nickel zinc ferrite-ethylene glycol), Fe2O4—C2H6O2 (magnetite ferrite-ethylene glycol), NiZnFe2O4—H2O (Nickel zinc ferrite-water), MnZnFe2O4—H2O (manganese zinc ferrite-water), and Fe2O4—H2O (magnetite ferrite-water) nanofluids containing manganese zinc ferrite, Nickel zinc ferrite, and magnetite ferrite nanoparticles dispersed in a base fluid of ethylene glycol and water mixture. The performance of convective heat transfer is elevated in boundary layer flow region via nanoparticles. Magnetic dipole in presence of ferrites nanoparticles plays a vital role in controlling the thermal and momentum boundary layers. In perspective of this, the impacts of magnetic dipole on the nano boundary layer, steady, and laminar flow of incompressible ferromagnetic nanofluids are analyzed in the present study. Flow is caused by linear stretching of the surface. Fourier’s law of heat conduction is used in the evaluation of heat flux. Impacts of emerging parameters on the magneto—thermomechanical coupling are analyzed numerically. Further, it is evident that Newtonian heating has increasing behavior on the rate of heat transfer in the boundary layer. Comparison with available results for specific cases show an excellent agreement.