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20p13 telomeric/subtelomeric deletions are clinically significant but are currently under-investigated. So far only five molecularly delineated cases have been reported in literature and no candidate genes have been sufficiently implicated. Here, we present six new deletion cases identified by chromosomal microarray analysis (CMA). We also review 32 cases combined from literature and databases. We found that most 20p13 deletion patients exhibit significant developmental delay. Dysmorphic features are common but a consistent pattern was not recognized. Reduced cognitive ability was frequent. Based on pathogenic deletions delineated in this study, we mapped the smallest overlapping region and identified two nervous system expressing genes (SOX12 and NRSN2) as candidate genes that may be involved in the developmental defects in 20p13 microdeletion., (© 2013 Wiley Periodicals, Inc.)

The 16p11.2 deletion is a recurrent genomic event and a significant risk factor for autism spectrum disorders (ASD). This genomic disorder also exhibits extensive phenotypic variability and diverse clinical phenotypes. The full extent of phenotypic heterogeneity associated with the 16p11.2 deletion disorder and the factors that modify the clinical phenotypes are currently unknown. Multiplex families with deletion offer unique opportunities for exploring the degree of heterogeneity and implicating modifiers. Here we reported the clinical and genomic characteristics of three 16p11.2 deletion carriers in a Chinese family. The father carries a de novo 16p11.2 deletion, and it was transmitted to the proband and sib. The proband presented with ASD, intellectual disability, learning difficulty, congenital malformations such as atrial septal defect, scoliosis. His dysmorphic features included myopia and strabismus, flat and broad nasal bridge, etc. While the father shared same neurodevelopmental problems as the proband, the younger brother did not show many of the proband's phenotypes. The possible unmasked mutation of TBX6 and MVP gene in this deleted region and the differential distribution of other genomic CNVs were explored to explain the phenotypic heterogeneity in these carriers. This report demonstrated the different developmental trajectory and discordant phenotypes among family members with the same 16p11.2 deletion, thus further illustrated the phenotypic complexity and heterogeneity of the 16p11.2 deletion., (Copyright © 2010 Wiley-Liss, Inc.)

In the distorted W-shaped mol-ecule of the title compound, C(17)H(12)N(6)O(3)S(2), a twofold axis passes through the carbonyl group. The mol-ecules stack in the crystal through π-π inter-actions [centroid-centroid distance = 3.883 Å] and weak C-H⋯N hydrogen-bonding inter-actions, forming a three-dimensional architecture.

In the title complex, [Zn(C(10)H(6)N(3)O(4))(2)(H(2)O)(2)], the Zn(II) atom is located on a twofold rotation axis and is coordinated by two trans-positioned N,O-bidentate and zwitterionic 5-carb-oxy-4-carboxyl-ato-2-(4-pyridinio)-1H-imidazol-1-ide (H(2)PIDC(-)) ligands and two water mol-ecules, defining a distorted octa-hedral environment. The complete solid-state structure can be described as a three-dimensional supra-molecular framework, stabilized by extensive hydrogen-bonding inter-actions involving the coordinated water mol-ecules, uncoordin-ated imidazole N atom, protonated pyridine N and carboxyl-ate O atoms of the H(2)PIDC(-) ligands.

Research has implicated mutations in the gene for neurexin-1 (NRXN1) in a variety of conditions including autism, schizophrenia, and nicotine dependence. To our knowledge, there have been no published reports describing the breadth of the phenotype associated with mutations in NRXN1. We present a medical record review of subjects with deletions involving exonic sequences of NRXN1. We ascertained cases from 3,540 individuals referred clinically for comparative genomic hybridization testing from March 2007 to January 2009. Twelve subjects were identified with exonic deletions. The phenotype of individuals with NRXN1 deletion is variable and includes autism spectrum disorders, mental retardation, language delays, and hypotonia. There was a statistically significant increase in NRXN1 deletion in our clinical sample compared to control populations described in the literature (P = 8.9 x 10(-7)). Three additional subjects with NRXN1 deletions and autism were identified through the Homozygosity Mapping Collaborative for Autism, and this deletion segregated with the phenotype. Our study indicates that deletions of NRXN1 predispose to a wide spectrum of developmental disorders.

In the title complex, [Fe(C(10)H(6)N(3)O(4))(2)(H(2)O)(2)], the Fe(II) atom is located on an inversion centre and is trans-coordinated by two N,O-bidentate 5-carb-oxy-2-(3-pyrid-yl)-1H-imidazole-4-carb-oxy-l-ate ligands and two water mol-ecules, defining a distorted octa-hedral environment. A two-dimensional network of N-H⋯O and O-H⋯O hydrogen bonds extending parallel to (110) helps to stabilize the crystal packing.

In the title complex, [Fe(C(10)H(6)N(3)O(4))(2)(H(2)O)(2)], the Fe(II) atom is located on a twofold rotation axis and is coordinated by two trans-positioned N,O-bidentate and zwitterionic 5-carboxy-2-(pyridinium-4-yl)-1H-imidazol-1-ide-4-carboxylate H(2)PIDC(-) ligands and two water mol-ecules in a distorted environment. In the crystal packing, a three-dimensional network is constructed via hydrogen-bonding involving the water mol-ecules, uncoordinated imidazole N atom, protonated pyridine N and carboxyl-ate O atoms.

The title compound, [Cd(NCS)(2)(C(13)H(10)N(4)OS)(2)](n), contains SCN(-) anions acting as end-to-end bridging ligands which utilize both S and N atoms to link cadmium(II) centers into one-dimensional double chains. The multidentate 5-(4-pyridyl)-2-(2-pyridylmethylsulfanyl)-1,3,4-oxadiazole ligands behave as monodentate terminal ligands, binding metal centers only through the N atoms of the 4-pyridyl groups. Two types of eight-membered rings are formed by two SCN(-) anions bridging Cd(II) centers, viz. planar and chair conformation, which are alternately disposed along the same chain. Finally, chains define a two-dimensional array through two different interchain pi-pi stacking interactions.

Angelman syndrome (AS) is a profound disorder notable for mental retardation and severe language deficits that results from lack of function of the maternally inherited copy of the UBE3A gene. Chromosome deletions of 15q11q13, paternal uniparental disomy (UPD), UBE3A gene mutations, and imprinting center defects are all commonly recognized mechanisms that disrupt the function of the maternal copy of the UBE3A gene. We report here two patients with different atypical etiologies of AS. The first patient is a 3-year-old boy with global developmental delay, severe speech deficits, seizures, and very happy disposition. Southern blot analysis for the maternal and paternal chromosome 15 methylation products showed a mosaic methylation pattern, suggesting an imprinting center defect. The second patient is a 4(1/2)-year-old boy with global developmental delay, no expressive language, microcephaly, seizures, and ataxic gait. Array-based comparative genomic hybridization (CGH) demonstrated a loss in copy number for two overlapping clones encompassing the UBE3A gene, indicating a partial deletion within UBE3A. His mother, who was adopted, had an identical pattern, suggesting that her deletion was probably on her paternally imprinted allele. These patients illustrate the expanding spectrum of molecular findings in AS, reinforce the need to maintain suspicion when clinical features suggest AS but initial testing is normal, and show the power of CGH as a tool to uncover partial UBE3A deletions.

Hearing loss is a common congenital disorder that is frequently associated with mutations in the Cx26 gene (GJB2). Three recent reports that found a large deletion in another DFNB1 gene, Cx30 (GJB6), suggest that this defect may cause nonsyndromic recessive hearing loss through either a homozygous deletion of Cx30, or digenic inheritance of a Cx30 deletion and a Cx26 mutation in trans. We designed a simple diagnostic strategy with multiplex PCR followed by direct sequencing to allow for the simultaneous detection of Cx26 mutations and Cx30 deletions, and evaluated its effectiveness as a clinical genetic test by examining 200 DNA samples. In the 108 samples from deaf subjects, two digenic mutations were identified in Cx26 and Cx30 (E47X/342 kb deletion and 167delT/342 kb deletion); 69 had only Cx26 mutations (29 biallelic, 40 singleton), including two novel frameshift mutations 511-512insAACG and 358-360delAG; and 37 had no detectable mutation in either Cx26 or Cx30. Our deletion mapping suggested that the proximal breakpoint of all reported Cx30 large deletions are between the nucleotide 444 and 627 at the Cx30 coding region within a maximal interval of 78 or 184 bp. This simultaneous examination of Cx26 and Cx30 is a practical and efficient diagnostic approach for patients with nonsyndromic congenital deafness., (Copyright 2003 Wiley-Liss, Inc.)

Fusion of virus members from the Paramyxoviridae family involves two glycoproteins. They are termed attachment glycoprotein (HN, H or G) and fusion protein (F). The F protein contains two highly conserved heptad-repeat (HR) regions, HR1 and HR2. Through conformational changes in the F protein, HR1 and HR2 are believed to form a stable six-helix coiled-coil bundle during the membrane-fusion process. However, no crystal structure has yet been documented for this state in the Newcastle disease virus (NDV, a member of the Paramyxoviridae family) F protein, despite the recent success on its F(0) crystal structure (Chen et al., 2001), which was thought to represent the pre-fusion conformation of F glycoprotein. In this study, a single-chain polypeptide constructed by linking two truncated HR regions of the NDV F protein has been expressed, purified and crystallized by means of the hanging- or sitting-drop vapour-diffusion method. Crystals in hexagonal and trapezoid forms with a resolution limit of 2.6 A were obtained. These crystals belonged to space group C2, with unit-cell parameters a = 66.4, b = 38.2, c = 102.0 A, beta = 100.2 degrees. Crystals in the rhombic form with a resolution limit of 2.5 A were also obtained. These crystals belonged to space group P2(1), with unit-cell parameters a = 59.0, b = 31.9, c = 62.3 A, beta = 117.0 degrees. This will add to the repertoire of viral fusion protein post-fusion state structures and help further the understanding of the molecular mechanism of enveloped virus fusion.

Recent work has demonstrated that the dog posterior cricoarytenoid (PCA) muscle is composed of three neuromuscular compartments: a vertical, an oblique, and a horizontal. In this study, the human PCA muscle was examined for evidence of neural compartments. Fifteen human PCA muscles were processed by Sihler's stain, which renders the muscle translucent while counterstaining the nerve supply. The results clearly show that in all specimens the nerve supply of the human PCA muscle is separated into at least two main branches: one supplies the horizontal compartment and a second further subdivides to innervate both the vertical and oblique compartments. In 10 of the specimens, these nerve branches arose as separate branches from the recurrent laryngeal nerve. In all specimens, the nerve branch to the horizontal compartment was either combined or connected with the nerve branch to the interarytenoid muscle. The results suggest that the different compartments of the PCA muscle have distinct functions. In addition, the strong connections with the interarytenoid nerve complicate reinnervation procedures to reanimate a paralyzed or transplanted larynx.

The nerve supply of the human interarytenoid (IA) muscle has been controversial for more than a century. In this study the contribution of the recurrent and superior laryngeal nerves to the IA was investigated in 10 adult human larynges. The larynges were obtained from autopsies and processed with the modified Sihler's technique which clears soft tissue while staining nerve. The IA muscles were dissected off the specimens and transilluminated to demonstrate their nerve supply. The results demonstrated that all 10 IA muscles were bilaterally innervated by both recurrent laryngeal nerves (RLNs) as well as branches of both superior laryngeal nerves (SLNs). These nerves combined within the IA muscles to form a dense anastomotic plexus which was highly variable between specimens. The exact nature of the internal SLN neurons, whether motor or sensory, their innervation targets, or their function, were not discernible. Additional anatomic findings were the presence of large neural communications directly between the SLN and RLN, and smaller neural connections from side to side. All of these results disagree with currently accepted descriptions of laryngeal neuroanatomy.

The posterior cricoarytenoid (PCA) muscle is known to be active during phonation and respiration. The presence of muscle compartments (bellies) that might subserve these functions was investigated in the canine PCA by anatomical dissection and muscle fiber histochemistry. Five PCA muscles were microdissected and the origins and insertions of all muscle bundles were recorded. An additional six PCA muscles were frozen, sectioned, and stained for adenosine triphosphatase (ATPase) activity. The total number of fast- and slow-twitch fibers were counted and their proportion was determined for each region of the muscle. The PCA muscle was found to contain three distinct neuromuscular compartments. The vertical compartment is oriented at 24 degrees from true vertical, inserts on the lateral aspect of the muscular process of the arytenoid, and is composed of 65% type 2 (fast) muscle fibers. The oblique is oriented at 44 degrees from vertical, inserts on the top of the muscular process of the arytenoid, and is composed of 77% type 2 muscle fibers. The horizontal is oriented at 63 degrees from vertical, inserts on the medial aspect of the muscular process of the arytenoid, and is composed of 59% type 2 muscle fibers. The cricoarytenoid joint is capable of three arcs of motion and the physical arrangement of each compartment appears to correspond to each of these motions. Moreover, the histochemical profiles show that the activity of the three bellies is quite different. These results suggest that the different compartments of the PCA perform distinctive motions during phonation and inspiration.

There is anatomical and histological evidence for three functionally distinct muscle bellies in the canine posterior cricoarytenoid (PCA) muscle. This study attempted to define the exact nerve branching pattern to each muscle belly in 10 dogs using a modification of Sihler's neural staining technique. The results are presented here as photographs and schematic nerve maps which illustrate the following points. 1. the final terminal branches within the PCA do correspond to the three bellies of the PCA; 2. the initial nerve branch to the PCA is usually composed of multiple fascicles which rearrange before their final branching to the three bellies; 3. there is tremendous variability of the nerve branching patterns including bilateral asymmetry within the same animal; 4. the terminal branching within each belly can be surprisingly complex and contain multiple anastomoses; 5. the fast- and slow-twitch bellies of the PCA have different terminal branching patterns. These results support the functional subdivision of the canine PCA into three distinct neuromuscular compartments. This microanatomical technique appears useful for studying the basic neuromuscular organization of laryngeal muscles and their developmental and pathological changes.

The paired posterior cricoarytenoid (PCA) muscle has three separate muscle bellies that differ in muscle fiber type (percentage of fast vs. slow twitch) and electromyelographic activity, and, in addition, produce different movements of the arytenoids when stimulated. An investigation of the innervation of the muscle was undertaken to demonstrate the existence of separate functional units. The intramuscular nerve supply of the PCA from five sacrificed dogs were microdissected. The intramuscular nerves of three additional dogs were removed and stained for acetylcholinesterase, which differentiates axons bound for fast- and slow-twitch muscle, and sensory end organs. Three separate fascicles are described entering the PCA muscle from a single branch of the recurrent laryngeal nerve. The three fascicles differ in axon type composition and in sensory, autonomic, and motor percentages, with the ratio of fast twitch to slow twitch varying from 0.78 to 1.5 to 1.7 (P less than .05). This variation supports separate functional capabilities for the three muscle bellies of the PCA.

Botulinum toxin was recently approved for treating several head and neck dystonias. Paralysis of neighboring muscles is the major complication of its use. Spread of toxin from the injected muscle has been suggested as an etiology. This study examines how botulinum toxin crosses muscle fascia by a novel method of quantifying muscular paralysis. Botulinum toxin (0.2 to 10 U) was placed onto the fascia of rat tibialis anterior (TA) muscles (n = 6). Toxin was also placed on dose-matched muscles that had their fascia surgically removed (n = 6). Twenty-four hours later, the nerve to the tibialis anterior was electrically stimulated to deplete the muscle fibers of glycogen. Toxin-paralyzed fibers retained their glycogen and appeared purple on periodic acid-Schiff (PAS) stain. Botulinum toxin easily passed through muscle fascia even at subclinical doses. The presence of fascia reduced the spread of botulinum toxin by 23%. These results suggest that spread of botulinum toxin can be prevented only by delivering small doses to the center of a target muscle.