Influenza A (H1N1) in Hospitalized Children.

BACKGROUND: Influenza A (H1N1) is a contagious respiratory infection caused by the influenza A virus. In the majority of cases, H1N1 influenza is benign. However, it can be dangerous for infants and children with underlying chronic diseases. The severity of influenza depends on various factors, including the virulence of the virus strain, preexisting immunity level, and individual health conditions. The aim of this study is to describe the clinical profile of H1N1 influenza in hospitalized infants and children. METHODS: This is a prospective and descriptive study conducted from November 1, 2018, to January 31, 2024. In this study, we included all children under 14 years old hospitalized for suspected severe lower respiratory infection who had gone through virological testing. We used a multiplex polymerase chain reaction (PCR) kit: the Film Array-Respiratory Panel. Due to the depletion of multiplex PCR kits, this study continued using rapid influenza diagnostic tests based on immunochromatographic technique. RESULTS: We report 45 confirmed cases of H1N1 influenza, collected during the period from November 1, 2018, to January 31, 2024. The average age was 2 years and 4 months. The main reason for admission was respiratory distress found in all patients. In 53% of the cases, there was an associated comorbidity, including asthma (17 cases), prematurity (2 cases), congenital adrenal hyperplasia (2 cases), cystic fibrosis (1 case), undetermined etiology bronchial dilation (1 case), and Basedow's disease (1 case). The clinical presentation included viral bronchiolitis (17 cases), moderate asthma exacerbation (10 cases), severe asthma exacerbation (7 cases), pneumonia (9 cases), bronchial dilation exacerbation (1 case), and flu-like syndrome with adrenal insufficiency (1 case). Fever was present in 31 patients. Gastrointestinal symptoms such as diarrhea and vomiting were present in 20 cases. Three patients required intensive care, with 2 children being intubated and ventilated (one severe acute asthma and one severe viral bronchiolitis). Two cases were treated with oseltamivir. The average length of hospital stay was 7.5 days, ranging from 3 to 20 days. All cases showed favorable evolution. CONCLUSIONS: We conclude that preventive measures remain crucial, and influenza vaccination is highly recommended in cases of underlying morbidity.

Polymorphisms of Tumor Necrosis Factor Alpha in Moroccan Patients with Gastric Pathology: New Single-Nucleotide Polymorphisms in TNF-α(-193) (G/A).

Polymorphisms in tumor necrosis factor alpha (TNF-α) gene are emerging as key determinants of gastric diseases. The TNF-α(-308) (G/A) and TNF-α(-238) (G/A) single-nucleotide polymorphisms SNPs are the most extensively studied. However, all these studies are conducted in Caucasian and Asian populations. Thus, for the first time in Africa, we sought to investigate whether polymorphisms in TNF-α gene were associated with the development of gastric pathology in Morocco. Two SNPs located in the promoter region (positions -308 and -238) in TNF-α gene were genotyped in 244 individuals (170 patients and 74 healthy controls). Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression analysis. The TNF-α(-238) (G/A) genotype was significantly associated with a high risk of gastritis and gastric cancer (GC) (P = 0.001 and P = 0.002, resp.). Furthermore, a new polymorphism located in the promoter region at position -193 in TNF-α gene was identified. The distribution of this SNP was markedly different in patients suffering from ulcers. The association between TNF-α(-193) (G/A) genotype and high risk of ulcer was significant (P = 0.03). These results suggest that the TNF-α(-193) (G/A) allele has a protective function against gastric cancer by developing ulcer.

Orbital metastases from prostate adenocarcinoma: Case report and review of the literature.

Introduction: Prostate carcinoma metastasizes usually to lymph nodes and bone. Its metastases to the orbital cavity remain very rare. Observation: We report here the case of an 80-year-old man diagnosed with a non-metastatic prostate adenocarcinoma 9 months earlier, who was found to have an orbital metastasis revealed by a proptosis of his left eye. He received hormonal therapy, chemotherapy and radiotherapy. Discussion: Orbital metastases from prostate carcinoma have many similarities to other orbital metastases in their presentation. Their diagnosis is easily done when there is a history of a primary tumor. Presenting symptoms include proptosis, limitation of eye movements, diplopia and decreased vision. Conclusion: Through this case report and a review of literature, we discuss the incidence, the clinical presentation and the management of these tumors.

Leber's idiopathic stellate neuroretinitis: A clinical case.

Introduction: In 1916, Leber's idiopathic stellate neuroretinitis (LISN) was described by Theodore Leber as a rare disease characterized by optic disc swelling associated with a macular star. This fundus appearance can have multiple causes but the etiology of Leber's idiopathic stellate neuroretinitis remains unknown. Case report: A 40 year-old man consulted for a progressive decline in visual acuity and a blurred vision in his left eye. Corrected Visual acuity of the left eye was hand motion, Funduscopy of the left eye revealed a stellate maculopathy with loss of foveolar depression and a normal optic disc. The angiography confirmed an optic disc oedema. Laboratory investigations were normal. No infectious nor inflammatory etiology was found. Brain imaging was normal. Patient received 3 days of intravenous methylprednisolone at 10mg/kg/D for 3 days in a row and an oral relay was started with a progressive degression over 2 weeks. The evolution after treatment was satisfactory, the visual acuity 3 weeks after the intravenous injection of corticoids increased to 2/10. Discussion: Leber's idiopathic stellate neuroretinitis (LISN) is a disorder characterized by disc oedema, peripapillary and macular hard exudates and, often, the presence of vitreous cells. The changes in the optic nerve are the primary cause of reduced vision in this condition. The more common treatable causes must be excluded wich are cat scratch disease (CSD) and vascular disease. 50% of cases have no identifiable cause and are labeled idiopathic neuroretinitis. There is no consensus regarding optimal treatment. The prognosis of Leber's idiopathic stellate neuroretinitis is good in most cases. Conclusion: The cause of neuroretinitis must be aggressively pursued before a diagnosis of lebre's idiopathic neuroretinis can be retained in order to formulate an appropriate treatment strategy.

Sclerochoroidal calcification associated with chondrocalcinosis: A clinical case.

INTRODUCTION: Sclerochoroidal calcifications is a rare condition corresponding to senile plaques due to the deposition of calcium and phosphate in the sclera and choroid. It is an elderly patient's pathology. In most cases, it is idiopathic. However, some patients have systemic disorders leading to disturbances in phosphocalcic metabolism, which are at the origin of this disorder. A check-up is therefore necessary to detect them. OBSERVATION: We report the case of a 65 year old patient admitted to the ophthalmology department for a renewal of optical correction. The patient is known to have articular chondrocalcinosis on anti-inflammatory medication. Fundus examination revealed multiple white supra macular choroidal lesions with tumour-like appearance in both eyes. The ultrasound perfomed showed the calcic nature of the lesions. Fluorescein and indocyanine green angiograms showed no sign of activity or presence of neovessels.A complete metabolic work-up, mainly phosphocalcic, was ordered again and the systemic diagnosis of articular chondrocalcinosis was retained. DISCUSSION: Shields et al. first described, in 1997, a case of sclerochoroidal calcification in a patient with chondrocalcinosis and a normal metabolic profile. Few more have been added to the literature. It is generally considered to be predominantly bilateral and is most often seen as yellowish lesions. Two types of calcifications have been described to date, the plaque type and the pseudotumor type. Given the asymptomatic presentation, a fundus examination should be performed in patients with chondrocalcinosis. Generally, no treatment is necessary. CONCLUSION: Sclerochoroidal calcifications usually manifests as multiple discrete yellow placoid lesions in elderly asymptomatic patients. Visual prognosis for sclerochoroidal classification is good since the lesions tend to be away from the macula. They should not be confused with choroidal metastasis or achromic melanoma which require more extensive treatment.

Retinal angioma of Von hippel-lindau disease: A case report.

INTRODUCTION: Von Hippel-Lindau disease (VHL), also known as Von Hippel-Lindau syndrome, is a rare genetic disorder with multisystem involvement. It is characterised by the development of multiple vascularised tumours, particularly cerebellar, retinal and/or visceral. The disease can occur at any age and usually starts with retinal hemangioblastomas. CASE REPORT: We report the case of a 45-year-old female patient with no particular pathological history, who. consulted the ophthalmology department for a change of optical correction.The funds examination showed an uncomplicated bilateral hemangioma with no other associated signs. Fluorescein angiography confirmed the diagnosis by showing in the left eye a multiple retinal hemangioma visible in the mid-periphery facing the branches of the superior temporal arches. The brain MRI showed a multifocal hemangioblastoma in the posterior cerebral fossa. A renal ultrasound returned normal. The patient had undergone photocoagulation of the retinal lesions to avoid any complications. DISCUSSION: The German ophthalmologist Eugen von Hippel first described angiomas in the eye. The term Von Hippel-Lindau disease was first used in 1936; however, its use became common only in the 1970s.Tumours called hemangioblastomas are characteristic of von Hippel-Lindau syndrome. These growths are made of newly formed blood vessels and occurs in the periphery of the retina. Spontaneous progression occurs leading to visual impairment as a result of maculopathy or exudative retinal detachment.Early recognition and treatment of specific manifestations of VHL can substantially decrease complications and improve quality of life.Conventional treatment of the retinal hemangioblastomas is laser photocoagulation or cryotherapy depending on the location and size of the lesions. It must be based on the patient's visual symptoms and tumor progression. CONCLUSION: Management of patients with VHL disease often requires a multidisciplinary approach. The role of the ophthalmologist is important in the management of this condition since the ocular involvement may be indicative of the disease.

13q interstitial deletion in a moroccan child with hereditary retinoblastoma and intellectual disability: A case report.

Retinoblastoma is the most common malignant tumor of the eye in children (incidence:1/15,000 to 1/20,000 births), with a sex ratio of 1,5/1. Retinoblastoma, in its inherited form, is a disease caused by a syndrome of genetic predisposition to cancer. The RB1 gene, a tumor suppressor gene, is localized at 13q14. This case report shows the indication of the cytogenetic analysis in the management of patients with retinoblastoma, and the interest of a genetic counseling. We report the medical observation of a five and a half years old patient who was followed in the medical genetic's department for intellectual disability: associated with facial dysmorphia. The cytogenetic study objectified the presence of an interstitial deletion of the long arm of chromosome 13: 46, XX, del (13) (q14q22). A genetic counseling, with study of the karyotype of the parents is planned, specially to search for a balanced insertion: 13q14 insertion and deletion. In addition, the patient has been followed since the age of 9 months at the pediatric ophthalmology department for a bilateral retinoblastoma, in remission. A subject carry in constitutional mutation of the RB1 gene has a greater than 90% risk of developing retinoblastoma, and moreover has a genetic predisposition to secondary tumors. This medical observation shows the benefit of the constitutional cytogenetic study for patients with retinoblastoma, in particular in the event of bilateral retinoblastoma. The monitoring of psychomotor development must supplement the ophthalmological monitoring of these patients, with a systematic genetic counseling.

[Manifestation of congenital rubella syndrome: clinical and epidemiologic aspects]. / Les manifestations ophtalmologiques de la rubéole congénitale: aspects cliniques et épidémiologiques.

INTRODUCTION: Congenital rubella syndrome is an ensemble of congenital malformations which results from a primary viral infection in non-immunised pregnant women. The main ophthalmologic manifestation is cataract. It involves at the same time visual and vital prognosis and can be responsible for multiple handicaps. METHODS: We did a retrospective study of 16 infants (32 eyes) having undergone congenital cataract surgery compatible with congenital rubella syndrome in the Casablanca paediatric ophthalmology department between January 2001 and December 2005. All the patients underwent a complete ophthalmologic examination, otorhinolaryngologic, cardiovascular and neurological examinations, and paraclinic explorations. RESULTS: The results were compared with those reported in the literature. In our series, 25 eyes (78.12%) had a cataract of which 56% were nuclear, 13 eyes (40.62%) had microphthalmia. One case each of corneal dystrophy and iris coloboma were described. Congenital glaucoma was found in only one case. Pigmentary retinopathy was found in 12 eyes (37.5%). Seven patients (43.75%) had associated cardiac anomalies, 6 (37.5%) deafness, 5 (31.25%) psychomotor delay and 2 (12.5%) facial dysmorphy. CONCLUSION: Considering the permanent disabilities caused by congenital rubella syndrome, care should be taken with the follow-up of the pregnancies and an immunization program should be implemented for good control of the circulation of the virus.

Mutational heterogeneity in low-density lipoprotein receptor gene related to familial hypercholesterolemia in Morocco.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Until now, molecular data concerning FH in Morocco is still limited. To gain more information in this field and to assess the contribution of these three genes in the cause of FH determinism, we analyzed six unrelated Moroccan probands and twenty-five of their family's members. METHODS: After LDLR and APOB genotype analysis, we screened the LDLR gene for mutations using southern blot and PCR-sequencing analysis. We also screened the APOB gene for the two common mutations R3500Q and R3531C by PCR-mediated site-directed mutagenesis. The PCSK9 gene was analyzed by direct sequencing. RESULTS: We identified three novel mutations (C25X, IVS3+5G>T, D558A) and two mutations previously described (D151N, A480E) in the LDLR gene. The R3500Q and R3531C mutations are absent in our probands and for 1 proband, the implication of LDLR, APOB and PCSK9 genes was excluded, supporting the implication of a fourth gene in the determination of FH. CONCLUSION: These data are in agreement with our previous study that suggests a heterogeneous mutational spectrum of FH in Morocco.

Interlocked mismatch-aligned arrowhead DNA motifs.

BACKGROUND: Triplet repeat sequences are of considerable biological importance as the expansion of such tandem arrays can lead to the onset of a range of human diseases. Such sequences can self-pair via mismatch alignments to form higher order structures that have the potential to cause replication blocks, followed by strand slippage and sequence expansion. The all-purine d(GGA)n triplet repeat sequence is of particular interest because purines can align via G.G, A.A and G.A mismatch formation. RESULTS: We have solved the structure of the uniformly 13C,15N-labeled d(G1-G2-A3-G4-G5-A6-T7) sequence in 10 mM Na+ solution. This sequence adopts a novel twofold-symmetric duplex fold where interlocked V-shaped arrowhead motifs are aligned solely via interstrand G1.G4, G2.G5 and A3.A6 mismatch formation. The tip of the arrowhead motif is centered about the p-A3-p step, and symmetry-related local parallel-stranded duplex domains are formed by the G1-G2-A3 and G4-G5-A6 segments of partner strands. CONCLUSIONS: The purine-rich (GGA)n triplet repeat sequence is dispersed throughout the eukaryotic genome. Several features of the arrowhead duplex motif for the (GGA)2 triplet repeat provide a unique scaffold for molecular recognition. These include the large localized bend in the sugar-phosphate backbones, the segmental parallel-stranded alignment of strands and the exposure of the Watson-Crick edges of several mismatched bases.

[Bilateral optic neuropathy and non-Hodkin's lymphoma]. / Neuropathie optique bilatérale et lymphome non Hodgkinien.

UNLABELLED: While ocular lesion is commonly known in lymphoma, optic neuropathy is very rare : 1,3% of lymphomas affecting the central nervous systems. OBSERVATION: Authors report the case of a 75 year old patient treated in the haematology department for 8 years, for a large cell B phenotype stage IV lymphoma for which he received 7 chemotherapy courses (CHOP protocol). After a 4 year remission period, he presented a relapse with a rapid progressive bilateral impairment of visual acuity observed for a week before his admission. The ophthalmologic exam revealed no light perception and no afferent reflex on the right eye. There was light perception and weak afferent reflex on the left eye. The anterior segment was normal on both eyes and fundus examination revealed a bilateral stage I papillar oedema. The general exam showed a right facial palsy and an impairment of general condition. The orbital CT scan revealed a significant thickening of both optic nerves caused by lymphomatous infiltration. A chemotherapy with highly dosed IV and intrathecal methotrexate was performed. DISCUSSION: the optic neuropathy is usually associated with a generalized lymphoma with central nervous system involvement, but sometimes can precede the systemic spread of the disease. Apart from infiltration, the optic nerve can be compressed by an intracranial or orbital tumor. The optic neuropathy can also be caused by lymphomatous leptomeningitis.

[Evaluation of the iliac crest as anatomic landmark for spinal anaesthesia in pregnant women]. / Evaluation de la crête iliaque comme repère anatomique de l'anesthésie rachidienne chez la femme enceinte à terme.

OBJECTIVE: Estimate the relevance of the Tuffier line, which connects both iliac crests, in analyzing the location of the puncture point for spinal anaesthesia for pregnant women. STUDY DESIGN: Prospective. PATIENTS AND METHODS: The age, weight, height, body mass index (BMI) and uterine height, (HU) of 121 patients admitted in the delivery room in July 2005, were recorded. The intersection point of the Tuffier line with the rachis was recorded in seating and sleeping positions. The corresponding vertebral level was verified by counting spiny apophyses from C7. RESULTS: The Tuffier line crossed the spine at the expected level for 29.7% of the patients. The intersection point was below the expected in 6.6% of the cases and above in 63.7% of the cases. Only the weight and the BMI were significantly connected with stronger probability of error (p=0.001). CONCLUSION: The error level with this method is important and comparable to error level in the series published in patients who are not pregnant woman. The main risk is the spinal injury, since the level of ending of the spinal cord is variable. It seems safe to use another method of location, especially with patients experiencing excessive weight.

Solution structure of a DNA quadruplex containing the fragile X syndrome triplet repeat.

Both X-ray and NMR structural studies have defined the polymorphic nature of G-quadruplexes generated through mutual stacking of G.G.G.G tetrads by guanine rich telomeric sequences. Recently, the fragile X syndrome d(C-G-G)n triplet nucleotide repeat has been shown to form a stable quadruplex of undefined structure in monovalent cation solution. We have undertaken a structural characterization of the d(G-C-G-G-T3-G-C-G-G) undecanucleotide to elucidate the structural alignments associated with quadruplex formation by this oligomer which contains sequence elements associated with the fragile X syndrome triplet repeat. d(G-C-G-G-T3-G-C-G-G) in Na+ cation solution forms a quadruplex through dimerization of two symmetry related hairpins with the lateral connecting T3 loops positioned at opposite ends of the quadruplex. This novel NMR-molecular dynamics based solution structure contains internal G.C.G.C tetrads sandwiched between terminal G.G.G.G tetrads. Watson-Crick G.C base-pairs within individual hairpins dimerize through their major groove edges using bifurcated hydrogen bonds to form internal G(anti).C(anti).G(anti).C(anti) tetrads. Adjacent strands are anti-parallel to each other around the symmetric G-quadruplex which contains two distinct narrow and two symmetric wide grooves. By contrast, the terminal G-tetrads adopt G(syn).G(anti).G(syn).G(anti) alignments. The structure of the d(G-C-G-G-T3-G-C-G-G) quadruplex with its multi-layer arrangement of G.G.G.G and G.C.G.C tetrads greatly expands on our current knowledge of quadruplex folding topologies. Our results establish the pairing alignments that can be potentially utilized by the fragile X syndrome triplet repeat to form quadruplex structures through dimerization of hairpin stems. The formation of novel G.C.G.C tetrads through dimerization of Watson-Crick G.C base-pairs is directly relevant to the potential pairing alignments of helical stems in genetic recombination.

A K cation-induced conformational switch within a loop spanning segment of a DNA quadruplex containing G-G-G-C repeats.

We have identified a unique structural transition (in slow exchange on the NMR time scale) in the tertiary fold of the d(G-G-G-C-T4-G-G-G-C) quadruplex on proceeding from Na+ to K+ as counterion in aqueous solution. Both monovalent cation-dependent conformations exhibit certain common structural features, which include head-to-tail dimerization of two symmetry-related stem-hairpin loops, adjacent strands which are antiparallel to each other and adjacent stacked G(syn).G(anti). G(syn).G(anti) tetrads in the central core of the quadruplexes. The Na and K cation stabilized structures of the d(G-G-G-C-T4-G-G-G-C) quadruplexes differ in the conformations of the T-T-T-T loops, the relative alignment of G.C base-pairs positioned opposite each other through their major groove edges and potentially in the number of monovalent cation binding sites. We have identified potential K cation binding cavities within the symmetry-related T-T-T-G segments, suggesting the potential for two additional monovalent cation binding sites in the K cation-stabilized quadruplex relative to its Na cation-stabilized counterpart. Modeling studies suggest that the major groove edges of guanine residues in Watson-Crick G.C base-pairs could potentially be bridged by coordinated K cations in the d(G-G-G-C-T4-G-G-G-C) quadruplex in KCl solution in contrast to formation of G.C.G.C tetrads for the corresponding quadruplex in NaCl solution. Our results defining the molecular basis of a Na to K cation-dependent conformational switch in the loop spanning segment of the d(G-G-G-C-T4-G-G-G-C) quadruplex may have relevance to recent observations that specific K cation coordinated loop conformations within quadruplexes exhibit inhibitory activity against HIV integrase.

A diamond-shaped zipper-like DNA architecture containing triads sandwiched between mismatches and tetrads.

The present study reports on the solution structure of the guanine plus adenine rich d(A(2)G(2)T(4)A(2)G(2)) 12-mer sequence which forms a unique fold in moderate NaCl solution. Proton resonance assignments for this sequence, which contains a pair of AAGG repeats separated by a T(4) linker segment, were aided by site-specific (15)N-labeling of guanine and adenine bases, as well as site-specific incorporation of 2,6-diaminopurine and 8-bromoadenine for adenine, 8-bromoguanine, 7-deazaguanine and inosine for guanine, and uracil and 5-bromouracil for thymine. The solution structure, which was solved by a combined NMR and intensity-refined computational approach, consists of a diamond-shaped architecture formed through dimerization of a pair of d(A(2)G(2)T(4)A(2)G(2)) hairpins. This 2-fold symmetric structure contains a quadruplex core consisting of a pair of symmetry-related G(syn).G(syn).G(anti). G(anti) tetrads, where adjacent strands have both parallel and anti-parallel neighbors and connecting T(4) segments which form diagonal loops. Each of the G(syn).G(syn).G(anti).G(anti) tetrads forms a platform on which stacks a T(anti).[A(syn)-A(anti)] triad containing a novel A(syn)-A(anti) platform step and a reversed Hoogsteen A(syn).T(anti) pair. We observe both base-base and base-sugar stacking interactions, with the latter occuring at a sheared A-G step where the sugar of the A stacks on the purine plane of the G. Unexpectedly, the topology of this sheared A(anti)-G(syn) step has many similarities with the C(anti)-G(syn) step in left-handed Z-DNA. The T.(A-A) triad is sandwiched between the G-tetrad on one side and a reversed Hoogsteen A(anti).T(anti) pair on the other. This intercalative topology is facilitated by a zipper-like motif where the A(anti) residue of the triad is interdigitated within a stretched A(anti)-G(syn) step. Our structural study reports on new aspects of A-A platforms, base triads, zipper-like interdigitation and sheared base steps, together with base-base and base-sugar stacking defining a diamond-like architecture for the d(A(2)G(2)T(4)A(2)G(2)) sequence. One can anticipate that mixed guanine-adenine sequences will exhibit a rich diversity of polymorphic architectures that will provide unique topologies for recognition by both nucleic acids and proteins.

Dimeric DNA quadruplex containing major groove-aligned A-T-A-T and G-C-G-C tetrads stabilized by inter-subunit Watson-Crick A-T and G-C pairs.

We report on an NMR study of unlabeled and uniformly 13C,15N-labeled d(GAGCAGGT) sequence in 1 M NaCl solution, conditions under which it forms a head-to-head dimeric quadruplex containing sequentially stacked G-C-G-C, G-G-G-G and A-T-A-T tetrads. We have identified, for the first time, a slipped A-T-A-T tetrad alignment, involving recognition of Watson-Crick A-T pairs along the major groove edges of opposing adenine residues. Strikingly, both Watson-Crick G-C and A-T pairings within the direct G-C-G-C and slipped A-T-A-T tetrads, respectively, occur between rather than within hairpin subunits of the dimeric d(GAGCAGGT) quadruplex. The hairpin turns in the head-to-head dimeric quadruplex involve single adenine residues and adds to our knowledge of chain reversal involving edgewise loops in DNA quadruplexes. Our structural studies, together with those from other laboratories, definitively establish that DNA quadruplex formation is not restricted to G(n) repeat sequences, with their characteristic stacked uniform G-G-G-G tetrad architectures. Rather, the quadruplex fold is a more versatile and robust architecture, accessible to a range of mixed sequences, with the potential to facilitate G-C-G-C and A-T-A-T tetrad through major and minor groove alignment, in addition to G-G-G-G tetrad formation. The definitive experimental identification of such major groove-aligned mixed A-T-A-T and G-C-G-C tetrads within a quadruplex scaffold, has important implications for the potential alignment of duplex segments during homologous recombination.

Solution structure of a Na cation stabilized DNA quadruplex containing G.G.G.G and G.C.G.C tetrads formed by G-G-G-C repeats observed in adeno-associated viral DNA.

We have applied NMR and molecular dynamics computations including intensity based refinement to define the structure of the d(G-G-G-C-T4-G-G-G-C) dodecanucleotide in 100 mM NaCl solution. The G-G-G-C sequence is of interest since it has been found as tandem repeats in the DNA sequence of human chromosome 19. The same G-G-G-C sequence is also seen as islands in adeno-associated virus, a human parvovirus, which is unique amongst eukaryotic DNA viruses in its ability to integrate site-specifically into a defined region of human chromosome 19. The d(G-G-G-C-T4-G-G-G-C) sequence forms a quadruplex in Na cation containing solution through head-to-tail dimerization of two symmetry-related stem-hairpin loops with adjacent strands antiparallel to each other around the quadruplex. The connecting T4 loops are of the lateral type, resulting in a quadruplex structure containing two internal G.G.G.G tetrads flanked by G.C.G.C tetrads. The G(anti).G(syn).G(anti).G(syn) tetrads are formed through dimerization associated hydrogen bonding alignments of a pair of Hoogsteen G(anti).G(syn) mismatch pairs, while the G(anti).C(anti).G(anti).C(anti) tetrads are formed through dimerization associated bifurcated hydrogen bonding alignments involving the major groove edges of a pair of Watson-Crick G.C base-pairs. The quadruplex contains two distinct narrow and two symmetric wide grooves with extensive stacking between adjacent tetrad planes. The structure of the quadruplex contains internal cavities that can potentially accommodate Na cations positioned between adjacent tetrad planes. Three such Na cations have been modeled into the structure of the d(G-G-G-C-T4-G-G-G-C) quadruplex. Finally, we speculate on the potential role of quadruplex formation involving G.G.G.G and G.C.G.C tetrads during the integration of the adeno-associated parvovirus into its target on human chromosome 19, both of which involve stretches of G-G-G-C sequence elements.