scholarly journals The Study of a 231 French Patient Cohort Significantly Extends the Mutational Spectrum of the Two Major Usher Genes MYO7A and USH2A

2021 ◽  
Vol 22 (24) ◽  
pp. 13294
Author(s):  
Luke Mansard ◽  
David Baux ◽  
Christel Vaché ◽  
Catherine Blanchet ◽  
Isabelle Meunier ◽  
...  
Keyword(s):  
Massively Parallel Sequencing ◽  
Splice Variants ◽  
Usher Syndrome ◽  
Genetic Diagnosis ◽  
Autosomal Recessive Disorder ◽  
Severe Form ◽  
High Rate ◽  
Type I ◽  
Type Ii ◽  
Causal Genes

Usher syndrome is an autosomal recessive disorder characterized by congenital hearing loss combined with retinitis pigmentosa, and in some cases, vestibular areflexia. Three clinical subtypes are distinguished, and MYO7A and USH2A represent the two major causal genes involved in Usher type I, the most severe form, and type II, the most frequent form, respectively. Massively parallel sequencing was performed on a cohort of patients in the context of a molecular diagnosis to confirm clinical suspicion of Usher syndrome. We report here 231 pathogenic MYO7A and USH2A genotypes identified in 73 Usher type I and 158 Usher type II patients. Furthermore, we present the ACMG classification of the variants, which comprise all types. Among them, 68 have not been previously reported in the literature, including 12 missense and 16 splice variants. We also report a new deep intronic variant in USH2A. Despite the important number of molecular studies published on these two genes, we show that during the course of routine genetic diagnosis, undescribed variants continue to be identified at a high rate. This is particularly pertinent in the current era, where therapeutic strategies based on DNA or RNA technologies are being developed.

scholarly journals An Update on the Genetics of Usher Syndrome

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
José M. Millán ◽  
Elena Aller ◽  
Teresa Jaijo ◽  
Fiona Blanco-Kelly ◽  
Ascensión Gimenez-Pardo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Usher Syndrome ◽  
Severe Form ◽  
Vestibular Dysfunction ◽  
Type I ◽  
Type Ii ◽  
Genetic Origin ◽  
Vestibular Response

Usher syndrome (USH) is an autosomal recessive disease characterized by hearing loss, retinitis pigmentosa (RP), and, in some cases, vestibular dysfunction. It is clinically and genetically heterogeneous and is the most common cause underlying deafness and blindness of genetic origin. Clinically, USH is divided into three types. Usher type I (USH1) is the most severe form and is characterized by severe to profound congenital deafness, vestibular areflexia, and prepubertal onset of progressive RP. Type II (USH2) displays moderate to severe hearing loss, absence of vestibular dysfunction, and later onset of retinal degeneration. Type III (USH3) shows progressive postlingual hearing loss, variable onset of RP, and variable vestibular response. To date, five USH1 genes have been identified:MYO7A(USH1B),CDH23(USH1D),PCDH15(USH1F),USH1C(USH1C), andUSH1G(USH1G). Three genes are involved in USH2, namely,USH2A(USH2A),GPR98(USH2C), andDFNB31(USH2D). USH3 is rare except in certain populations, and the gene responsible for this type isUSH3A.

Cloning and Identification of Two Novel Splice Variants of Human PD-L2

2004 ◽  
Vol 36 (4) ◽  
pp. 284-289 ◽  
Author(s):  
Xian-Hui He ◽  
Yi Liu ◽  
Li-Hui Xu ◽  
Yao-Ying Zeng
Keyword(s):  
Posttranscriptional Regulation ◽  
Splice Variants ◽  
Expression Patterns ◽  
K562 Cells ◽  
Soluble Form ◽  
Acceptor Site ◽  
Type I ◽  
Type Ii ◽  
Variant Type ◽  
Frame Shift

Abstract PD-L2, a newly identified member of B7 family, plays a role in down-regulating T cell responses. The common PD-L2 mRNA (type I) is the splicing product containing all 6 exons. We report here the identification of two human PD-L2 splice variants in activated leukocytes. One splice variant (type II) is generated through splicing out exon 3 encoding Ig constant-like domain; it retains all other regions without a frame shift. The other variant (type III) is created by splicing out exon 3 to an alternative acceptor site 5 bp downstream of the canonical acceptor site, leading to a frame shift. Consequently, the translated protein should be a soluble form. Furthermore, type I isoform is expressed on the plasma surface whereas type II isoform showed a pattern of intracellular membrane distribution in the transiently transfected K562 cells. In addition, the expression patterns of PD-L2 splice variants are variable in different individuals and distinct cellular status. These results suggest that PD-L2 expression may be controlled by posttranscriptional regulation through alternative splicing, and modulation of PD-L2 isoform expression may influence the outcome of immune response.

Expression of fibronectin mRNA splice variants by rabbit lung in vivo and by alveolar type II cells in vitro

1996 ◽  
Vol 271 (6) ◽  
pp. L972-L980
Author(s):  
W. M. Maniscalco ◽  
R. H. Watkins ◽  
M. H. Campbell
Keyword(s):  
Gene Transcription ◽  
Splice Variant ◽  
Splice Variants ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
Injured Lung

Fibronectin (FN) is a multidomain glycoprotein with putative functions in tissue development and repair. In repair of alveolar injury, FN may promote the transition of type II epithelial cells to type I epithelial cells. Alternative splicing of FN mRNA, including the EIIIA and EIIIB exons, results in protein isoforms that have cell, tissue, and developmental specificity. The present work found that FN mRNA with the EIIIA exon was in fetal, adult, and oxidant-injured lung. The EIIIB splice variant, however, was restricted to fetal lung and adult lung recovering from oxidant injury. Because alveolar type II cells in vitro express FN, we examined the splice variants in two conditions that induce FN [transforming growth factor-beta 1 (TGF-beta 1) treatment and time in culture]. TGF-beta 1 increased both EIIIA and EIIIB mRNA abundance by 10-fold. Increased EIIIA isoform immunostaining was also noted. Type II cells that spontaneously express FN at 72 h in vitro had increased EIIIA and EIIIB mRNA and increased immunostaining for EIIIA. Nuclear runoff showed induction of FN gene transcription at 72 h in vitro. Together, these data show differential FN splice variant expression in lung, with EIIIB mRNA restricted to fetal and recovering oxidant-injured lung. Furthermore, the transition of type II cells to a type I-like cell is accompanied by increased FN gene transcription and induction of both EIIIA and EIIIB mRNA.

Neonatal Schwartz-Jampel syndrome type II: a rare case of peripheral origin of neonatal hypertonia

2021 ◽  
Vol 14 (7) ◽  
pp. e240397
Author(s):  
Arjun Verma ◽  
Nishant Banait ◽  
Pradeep Suryawanshi ◽  
Reema Garegrat
Keyword(s):  
Genetic Disorder ◽  
Receptor Gene ◽  
Genetic Diagnosis ◽  
Severe Form ◽  
Leukaemia Inhibitory Factor ◽  
Homozygous Mutation ◽  
Syndrome Type ◽  
Type Ii ◽  
Feeding Difficulties ◽  
Peripheral Origin

Neonatal Schwartz-Jampel syndrome type II is a rare and severe form of genetic disorder. Different from the classical appearance in infancy, neonatal presentation involves respiratory and feeding difficulties, along with characteristic pursed appearance of the mouth, myotonia, skeletal dysplasia and severe fatal hyperthermia. The clinical spectrum of this syndrome is so wide that it easily baffles with more common differentials. In this case report, a neonate born to third-degree consanguineous marriage with previous two abortions presented with respiratory difficulty, severe hyperthermia and feeding difficulty, which were daunting challenges to manage due to being refractory to standard line of management. Severe myotonia and gross dysmorphism were challenging dots to connect. Targeted exome sequencing was a ray of hope, which revealed homozygous mutation in the leukaemia inhibitory factor receptor gene on chromosome 5p13, confirming the genetic diagnosis for a fairly common spectrum of symptoms. The neonate later developed pneumoperitoneum and succumbed to underlying severe neonatal illness.

scholarly journals Types of Haemolytic Streptococci in Relation to Scarlet Fever (Second Report)

1927 ◽  
Vol 26 (4) ◽  
pp. 363-373 ◽  
Author(s):  
Fred Griffith
Keyword(s):  
Scarlet Fever ◽  
Severe Form ◽  
Type I ◽  
Type Ii ◽  
Fresh Blood ◽  
Type Iii ◽  
Type Iv ◽  
Differential Characters ◽  
Reliable Classification

A series of 222 strains has been analysed serologically and 156 have been found to react with one or other of four sera prepared with haemolytic streptococci of scarlatinal origin.Among the 156 strains the four chief types were distributed in the following proportions: 10 of Type I, 57 of Type II, 45 of Type III and 44 of Type IV.The remaining 66 strains of the series have not yet been classified; though they certainly include individualistic strains, there may be other types to be defined by further analysis.The four chief types are well defined and can generally be identified by direct agglutination. Cross-agglutination may cause confusion when suspensions are unstable, in which case resort must be made to agglutinin absorption. In addition, certain Type I strains may also agglutinate with Type III serum.Analysis of clinical data in a series of 100 cases shows clearly that a fairly severe form of scarlatina with greater tendency to complications is often caused by infection with Type II scarlatinal streptococcus; Type II has so far been found only in association with scarlet fever.There were nine instances where two or more members of the same family developed scarlatina; in six instances the same type was found in each patient and in three each patient yielded an unclassified strain. In one instance the strains from two members of the same family were different.Haemolytic streptococcus colonies on fresh blood agar present three chief varieties; there are minor differences between these dependent on the amount of moisture in the medium.There is a certain correlation between variety of colony and serological type. Type III colonies retain a soft consistency after two days' incubation, while the other types generally become tough and can be lifted from the medium as a whole.Rough and smooth colonies with differential characters analogous to those occurring in pneumococcus cultures have not been identified. An interesting change in appearance is the production of a clear dome-shaped watery or slightly mucinous colony (3rd variety) in a culture which ordinarily forms either more or less opaque or soft coherent colonies.There is evidence that the proportions of the four main types are likely to vary in different localities and in different outbreaks of scarlet fever in the same locality.The importance of a reliable classification of haemolytic streptococci is discussed.

scholarly journals 1305 FUNCTIONAL READOUT OF TMPRSS2-ERG TYPE I AND TYPE II SPLICE VARIANTS

2010 ◽  
Vol 183 (4S) ◽  
Author(s):  
Ying Hu ◽  
Taduru Sreenath ◽  
Albert Dobi ◽  
Shyh-Han Tan ◽  
Gyorgy Petrovics ◽  
...  
Keyword(s):  
Splice Variants ◽  
Type I ◽  
Type Ii

scholarly journals USH2 Caused by GPR98 Mutation Diagnosed by Massively Parallel Sequencing in Advance of the Occurrence of Visual Symptoms

2015 ◽  
Vol 124 (1_suppl) ◽  
pp. 123S-128S ◽  
Author(s):  
Hideaki Moteki ◽  
Hidekane Yoshimura ◽  
Hela Azaiez ◽  
Kevin T. Booth ◽  
A. Eliot Shearer ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Massively Parallel Sequencing ◽  
Usher Syndrome ◽  
Genetic Diagnosis ◽  
Massively Parallel ◽  
Parallel Sequencing ◽  
Visual Symptoms ◽  
Targeted Genomic Enrichment ◽  
Usher Syndrome Type

Objective: We present 2 patients who were identified with mutations in the GPR98 gene that causes Usher syndrome type 2 (USH2). Methods: One hundred ninety-four (194) Japanese subjects from unrelated families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes were used to identify the genetic causes of hearing loss. Results: We identified causative mutations in the GPR98 gene in 1 family (2 siblings). The patients had moderate sloping hearing loss, and no progression was observed over a period of 10 years. Fundus examinations were normal. However, electroretinograms revealed impaired responses in both patients. Conclusion: Early diagnosis of Usher syndrome has many advantages for patients and their families. This study supports the use of comprehensive genetic diagnosis for Usher syndrome, especially prior to the onset of visual symptoms, to provide the highest chance of diagnostic success in early life stages.

The use of Ellis pins (negative profile tip-threaded pins) in external skeletal fixation in dogs and cats

2003 ◽  
Vol 16 (04) ◽  
pp. 223-231 ◽  
Author(s):  
M. J. Pead ◽  
A. L. Beck
Keyword(s):  
High Rate ◽  
Type I ◽  
Type Ii ◽  
Chi Square ◽  
Exact Test ◽  
Risk Of Failure ◽  
Fisher’S Exact Test ◽  
Chi Square Test ◽  
Rate Of Failure

SummaryThe Ellis pin is commonly used in external skeletal fixators (ESFs) but some authors suggest that this pin suffers from a high rate of failure. The purpose of this study was to look for complications associated with four different pin types, in particular pin breakage, as well as pin loosening, radiolucency around pins and pin tract discharge. Fifty consecutive cases which had an ESF applied using Ellis pins were identified. Radiographs and case records were used to record case details, ESF design, duration of fixation, pin types used, and complications. Records from 31 dogs and 17 cats were examined (2 animals were removed from the study because of incomplete follow-up). There were 21 Type I, 7 Type I with a tied-in IM pin, 2 modified Type I, 2 modified Type I with a tied-in IM pin and 16 modified Type II ESFs. 160 Ellis pins, 30 centrally threaded positive profile pins, 4 end threaded positive profile pins and 46 smooth pins were used. Complications relating to one or more of the pins were seen in 65% of the fixators. None of the pins broke. There was a significant association between individual pin type and the number of pins showing loosening (p = 0.002) or radiolucency (p = 0.006), but not a significance in the association between pin type and discharge (Chi-Square test). When each pin was compared against each other pin, smooth pins were significantly more likely to be loose than Ellis pins (p <0.001), and centrally threaded positive profile pins were significantly more likely to result in radiolucency than Ellis pins (p = 0.01), using a Chi-square test. There was not any significant association between any other pin types for any complication using a Fisher’s Exact test. The study demonstrates that Ellis pins, when inserted correctly, are not at any greater risk of failure than other pin types, and that fewer complications may be associated with them than other pin designs.

Hearing Loss in Usher Syndrome Type II is Nonprogressive

2002 ◽  
Vol 111 (12) ◽  
pp. 1108-1111 ◽  
Author(s):  
Christoph F. V. Reisser ◽  
William J. Kimberling ◽  
Christian R. Otterstedde
Keyword(s):  
Hearing Loss ◽  
Hearing Aids ◽  
Visual Loss ◽  
Usher Syndrome ◽  
Autosomal Recessive Disorder ◽  
Syndrome Type ◽  
Type Ii ◽  
Subjective Impression ◽  
Communicative Abilities ◽  
Usher Syndrome Type

Usher syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss and progressive visual loss secondary to retinitis pigmentosa. In the literature, a possible progression of the moderate to severe hearing loss in Usher syndrome type II (Usher II) is controversial. We studied the development of the hearing loss of 125 patients with a clinical diagnosis of Usher syndrome type II intraindividually and interindividually by repeatedly performing complete audiological and neuro-otologic examinations. Our data show a very characteristic slope of the hearing curve in all Usher II patients and no clinically relevant progression of the hearing loss over up to 17 years. The subjective impression of a deterioration of the communicative abilities of Usher II patients must therefore be attributed to the progressive visual loss. The patients should be reassured that changes in their hearing abilities are unlikely and should be provided with optimally fitted modern hearing aids.

Usher syndrome

2021 ◽  
pp. 495-497
Author(s):  
Shanees. E
Keyword(s):  
Hearing Loss ◽  
Early Diagnosis ◽  
Vision Loss ◽  
Treatment Success ◽  
Usher Syndrome ◽  
Autosomal Recessive Disorder ◽  
Type I ◽  
Profound Hearing Loss ◽  
Balance Problems ◽  
Usher Syndrome Type

Usher syndrome is a condition that affects both hearing and vision; sometimes it also affects balance. The major symptoms of Usher syndrome are deafness or hearing loss and an eye disease called retinitis pigmentosa (RP). Most children with Usher syndrome are born with moderate to profound hearing loss, depending on the type. Less commonly, hearing loss from Usher syndrome appears during adolescence or later.1 Usher syndrome affects approximately 4 to 17 per 100,000 people,2,3 and accounts for about 50 percent of all hereditary deaf- blindness cases.4 . Usher syndrome is inherited as an autosomal recessive disorder. Usher syndrome is caused by mutations in specific genes. So far, Usher syndrome has been associated with mutations in at least ten genes. There are three types of Usher syndrome, type I, type II and type III 1. Diagnosis of Usher syndrome involves pertinent questions regarding the person’s medical history and testing of hearing, balance, and vision. Early diagnosis is important, as it improves treatment success. Genetic testing may help in diagnosing Usher syndrome. Presently, there is no cure for Usher syndrome. Treatment involves managing hearing, vision, and balance problems. Early diagnosis helps tailor educational programs that consider the severity of hearing and vision loss and a child’s age and ability.1 Usher Syndrome Awareness Day is observed in the third Saturday of September. Usher Syndrome Awareness Day seeks to bring attention and raise awareness of the most common genetic cause of combined deafness and blindness.5

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