SMN2 and NAIP gene dosages in Vietnamese patients with spinal muscular atrophy

Background: The SMN1 gene is now recognized as a spinal muscular atrophy (SMA)-causing gene, while SMN2 and NAIP have been characterized as a modifying factor of the clinical severity of SMA. Gene dosage of SMN2 is associated with clinical severity of SMA. But the relationship between gene dosage of NAIP and clinical severity of SMA remains to be clarified, although complete deletion of NAIP is frequent in type I patients.
Methods: To evaluate the contribution of the SMN2 and NAIP gene dosages to SMA, quantitative real-time polymerase chain reaction was used to measure copy numbers of SMN2 and NAIP in 34 Vietnamese SMA patients lacking SMN1 (13 type I, 11 type II and 10 type III patients).
Results: The SMN2 copy number in type I patients was significantly lower than that in type II–III patients, which was compatible with the previous reports. In contrast, 25 out of 34 patients had only zero or one copy of NAIP , while 50 out of 52 controls had two or more copies. For NAIP (+) genotype, six out of 13 type I patients, eight out of 11 type II patients and six out of 10 type III patients carried one NAIP copy.
Conclusions: The SMN2 copy number was related to the clinical severity of SMA among Vietnamese patients. The presence of one NAIP copy, that is, heterozygous NAIP deletion, was common in Vietnamese SMA, regardless of clinical phenotype.     

Deletion analysis of SMN1 exon 7 alone may be necessary and sufficient for the diagnosis of spinal muscular atrophy

The authors suggest a simplification for the current molecular genetic testing of spinal muscular atrophy (SMA). Deletion analysis of SMN1 exon 7 alone may be necessary and sufficient for the diagnosis of SMA. It is based on sole contribution of survival motor neuron 1 (SMN1) exon 7 to SMA pathogenesis.     

Surgical management of extreme lateral lumbar disc herniations: review of 138 cases

Extreme lateral disc herniations in the authors' series account for 10% of all lumbar herniations; 80% occurred at the L3, L4 and L4, L5 interspaces. The authors review the clinical findings in 138 patients and point to the characteristic features of the clinical syndrome. They compare the accuracy of various diagnostic studies and conclude that computed tomography is highly accurate and should be used before other diagnostic studies. Discography is still helpful as a confirmatory study in some cases, whereas myelography is particularly useful in disclosing other associated lesions. Analysis of the operative series revealed a high percentage of extruded fragments (60%) and a significant number of double herniations on the same side and at the same level (15%). These two findings may respectively preclude chemonucleolysis and microsurgery from the surgical management of extreme lateral herniations. Double herniations explain some discrepancies in the clinical picture and are emphasized as a potential source of error in diagnosis. The surgical technique allows exploration for herniations within the intervertebral canal as well as for extraforaminal herniations without sacrifice of the facet. Operative results are presented.     

Screening of the LIX1 gene in Japanese and Malaysian patients with SMA and/or SMA-like disorder

Background: The majority of spinal muscular atrophy (SMA) patients showed homozygous deletion or other mutations of SMN1. However, the genetic etiology of a significant number of SMA patients has not been clarified. Recently, mutation in the gene underlying cat SMA, limb expression 1 (LIX1), has been reported. Similarity in clinical and pathological features of cat and human SMA may give an insight into possible similarity of the genetic etiology. Patients and methods: In this study, we screened for a mutation in LIX1 using direct DNA sequencing in our SMA and/or SMA-like patients who retained SMN1. A total of 33 patients were enrolled in this study, of which 22 were Japanese and 11 were Malaysians. All these patients possessed at least two copies of SMN1. Results: We did not identify any pathogenic mutations in the coding regions or splice sites of LIX1 in the patients. In addition, we described a polymorphism within LIX1 intron 3, c.387 + 107A > T. We found that A-allele is significantly more frequent in SMA patients compared to normal individuals. Conclusion: Molecular genetic analysis of our SMA and/or SMA-like patients suggests that LIX1 is not associated with the development of their disorders. However, the number of patients analyzed in this study was very limited, and a larger study with bigger sample size is needed to confirm this result.     

A novel mutation at the N-terminal of SMN Tudor domain inhibits its interaction with target proteins

Abstract Although most patients with spinal muscular atrophy (SMA) are homozygous for deletion of the SMN1 gene, some patients bear one SMN1 copy with a subtle mutation. Detection of such an intragenic mutation may be helpful not only in confirming diagnosis but also in elucidating functional domains of the SMN protein. In this study, we identified a novel mutation in SMN1 of two Japanese patients with type I SMA. DHPLC and sequencing analysis revealed that they harbored a point mutation in SMN1 exon 3, 275G > C, leading to tryptophan-to-serine substitution at amino acid 92 (W92S) at the Nterminal of SMN Tudor domain. In-vitro protein binding assays showed that the mutation severely reduced interaction of the domain with SmB protein and fibrillarin, suggesting that it impairs the critical function of SMN. In conclusion, we reported here that a novel mutation, W92S, in the Tudor domain affects the interaction of SMN with the target proteins.     

Pozzolanic Activity Assessment of LUSI (LUmpur SIdoarjo) Mud in Semi High Volume Pozzolanic Mortar

LUSI mud obtained from the mud volcano in Sidoarjo, Indonesia, is a viable aluminosilicate material to be utilized as pozzolanic material. LUSI is an abbreviation of the local name of the mud, i.e., Lumpur Sidoarjo, meaning Sidoarjo mud. This paper reports the results of an investigation to assess the pozzolanic activity of LUSI mud, especially in semi high volume pozzolanic mortar. In this case, the amount of mud incorporated is between 30% to 40% of total cementitious material, by mass. The content of SiO₂ in the mud is about 30%, whilst the total content of SiO₂, Fe₂O₃ and Al₂O₃ is more than 70%. Particle size and degree of partial cement replacement by treated LUSI mud affect the compressive strength, the strength activity index (SAI), the rate of pozzolanic activity development, and the workability of mortar incorporating LUSI mud. Manufacturing semi high volume LUSI mud mortar, up to at least 40% cement replacement, is a possibility, especially with a smaller particle size of LUSI mud, less than 63 μm. The use of a larger percentage of cement replacement by LUSI mud does not show any adverse effect on the water demand, as the flow of the fresh mortar increased with the increase of percentage of LUSI mud usage.     

Spontaneous penetration of an antireflux prosthesis into the stomach

The Angelchik antireflux prosthesis is a ringlike device used in the surgical treatment of sliding hiatal hernia and gastroesophageal reflux. This article describes an unusual postoperative complication whereby the prosthesis had migrated into the lumen of the stomach.     

Spatial sensitivity of acousto-optic and optical near-infrared spectroscopy sensing measurements

Near-infrared spectroscopy (NIRS) is a popular sensing technique to measure tissue oxygenation noninvasively. However, the region of interest (ROI) is often beneath a superficial layer, which affects its accuracy. By applying focused ultrasound in the ROI, acousto-optic (AO) techniques can potentially minimize the effect of physiological changes in the superficial layer. Using absorption perturbation experiments in both transmission and reflection modes, we investigated the spatial sensitivity distributions and mean penetration depths of an AO system based on a digital correlator and two popular NIRS systems based on i. intensity measurements using a single source and detector configuration, and ii. spatially resolved spectroscopy. Our results show that for both transmission and reflection modes, the peak relative sensitivities of the two NIRS systems are near to the superficial regions, whereas those of the AO technique are near to the ROIs. In the reflection mode, when the ROI is deeper than 14 mm, the AO technique has a higher absolute mean sensitivity than the two NIRS techniques. As the focused ultrasound is moved deeper into the turbid medium, the mean penetration depth increases accordingly. The focused ultrasound can shift the peak relative sensitivity of the AO measurement toward its focused region.     

Effects of MTHFR c.677C>T,F2 c.20210G>A and F5 Leiden Polymorphisms in Gastroschisis

Background: Gastroschisis is a developmental disorder involving the extrusion of fetal intestines through a defect in the abdominal wall. The mechanism is presumed to be a dual vascular/thrombotic pathogenesis, where normal right umbilical vein involution forms a possible site for thrombosis adjacent to the umbilical ring. Purpose: The aim of this study was to demonstrate that the 3 common prothrombotic polymorphisms, MTHFR c.677C>T, F2 c.20210G>A, and F5 Leiden, were elevated in frequency in Indonesian gastroschisis patients. Material and Methods: Three genetic markers were investigated in 46 patients with gastroschisis and 89 ethnicity-matched controls for association studies using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) or TaqMan Genotyping Assays on genomic DNA. Results: MTHFR c.677C>T showed a significant association with gastroschisis (OR = 2.1, 95% CI = 1.13–3.86; p = .018) but no affected infants had risk alleles for either F2 c.20210G>A or F5 Leiden. Further, the frequency of MTHFR risk allele (T) in patients with maternal age <25 years is marginally significant higher than those in cases with maternal age ≥25 years (p = .069) with an OR of 2.7 (95% CI = 0.90–8.07). Conclusions: MTHFR is a common susceptibility factor for gastroschisis in Indonesia. The increased gastroschisis risk in offspring of younger maternal age suggests the thrombotic pathogenesis model. A founder effect is the most likely explanation for the rarity of the F2 and F5 Leiden polymorphisms in Indonesian population.