USH2A mutation and specific driver mutation subtypes are associated with clinical efficacy of immune checkpoint inhibitors in lung cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFRL858R and EGFRΔ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‍‒‍1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‍‒‍2.63; P<0.0001), while classical activating mutations with EGFRT790M showed no difference compared to classical activating mutations without EGFRT790M in OS (adjusted HR, 0.96; 95% CI, 0.48‍‒‍1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‍‒‍1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‍‒‍0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‍‒‍0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‍‒‍8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‍‒‍6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRASG12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFRT790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.

Retinitis pigmentosa in Usher syndrome in India: Electronic medical records driven big data analytics: Report III

Purpose: To describe the clinical presentation and demographic distribution of retinitis pigmentosa (RP) in patients with Usher syndrome (USH). Methods: This is a cross?sectional observational hospital?based study including patients presenting between March 2012 and October 2020. In total, 401 patients with a clinical diagnosis of USH and RP in at least one eye were included as cases. The data were retrieved from the electronic medical record database. For better analysis, all 401 patients were reclassified into three subtypes (type 1, type 2, and type 3) based on the USH criteria. Results: In total, there were 401 patients with USH and RP, with a hospital?based prevalence rate of 0.02% or 2/10,000 population. Further, 353/401 patients were subclassified, with 121 patients in type 1, 146 patients in type 2, and 86 patients in the type 3 USH group. The median age at presentation was 27 years (IQR: 17.5–38) years. There were 246 (61.35%) males and 155 (38.65%) females. Males were more commonly affected in all three subtypes. Defective night vision was the predominant presenting feature in all types of USH (type 1: 43 (35.54%), type 2: 68 (46.58%), and type 3: 40 (46.51%) followed by defective peripheral vision. Patients with type 2 USH had more eyes with severe visual impairment. Conclusion: RP in USH is commonly bilateral and predominantly affects males in all subtypes. Patients with USH and RP will have more affection of peripheral vision than central vision. The key message of our study is early visual and hearing rehabilitation in USH patients with prompt referral to otolaryngologists from ophthalmologists and vice versa.

Prevalence of ophthalmic disorders among hearing-impaired school children in Guntur district of Andhra Pradesh

Purpose: To estimate the prevalence, causes, and risk factors for visual impairment (VI) among children of school for hearing-impaired (HI) in Guntur district of Andhra Pradesh, India. Methods: Children between 6 and 16 years of age available in all the 12 special schools for HI were examined. Visual acuity (VA) testing, ocular motility, and examination of anterior and posterior segment for all children were done. Those having VA of less than 6/12 in better eye underwent cycloplegic refraction. For definition of VI, as per World Health Organization (WHO), VA of better eye was considered. HI was also classified as mild, moderate, severe, and profound as per WHO definitions. Examination for systemic diseases and other associated disabilities was also done. Results: In all, 402 children underwent examination. Ophthalmic abnormality was seen in 64 children with a prevalence of 15.9% [95% confidence interval (CI) 14.9%–16.8%], and VI was seen in 29 children with a prevalence of 7.2% (95% CI 4.9%–10.2%). Refractive errors [29 (7.2%)], retinitis pigmentosa (RP) [16 (4%)], and squint [8 (2%)] were the major ophthalmic abnormalities. Thirty-five (54.7%) of the abnormalities were either preventable or treatable. The major cause of VI was refractive error (18) followed by RP (5). Twenty of them (69%) with VI in this study group were treatable. Twenty-two (75.9%) children with eye problem were newly diagnosed. The only risk factor for VI was being mentally challenged (odds ratio: 5.63; 95% CI: 1.89–16.8). Conclusion: The prevalence of ophthalmic abnormalities and VI in school for HI was high, and the majority of them were not detected so far. As most of them are easily treatable, it is highly recommended to conduct regular eye examinations in these schools.

Comportamiento epidemiológico del síndrome de Usher en Holguín, Cuba / Usher syndrome epidemiological behavior in Holguín, Cuba

Introducción: el síndrome de Usher es una enfermedad genética con un patrón de herencia autosómico recesivo. Se caracteriza por hipoacusia neurosensorial bilateral, de moderada a profunda, y retinosis pigmentaria progresiva acompañada de disfunción auditiva, en algunos casos. Es la segunda causa de discapacidad visual y auditiva en el mundo. En Cuba, presenta una alta prevalencia en la provincia de Holguín. Objetivo: determinar el comportamiento epidemiológico del síndrome de Usher en la provincia de Holguín. Método: se realizó un estudio descriptivo retrospectivo de una serie de casos. El universo fue de 53 afectados, con diagnóstico clínico de Síndrome de Usher, los que fueron atendidos en el Centro Provincial de Retinosis Pigmentaria de Holguín, desde enero del 2009 a diciembre del 2016. Las variables estudiadas fueron: sexo, grupo de edades, cantidad de familias afectadas, matrimonios consanguíneos y municipio a los que pertenecen. Resultados: el 60,4% de los casos se presentó en el sexo masculino, y el 30,2% de estos, entre los 50 y 59 años de edad. Los municipios con un mayor número de matrimonios consanguíneos afectados fueron Holguín y Mayarí, con un 23 % y 21% respectivamente. Conclusiones: la práctica social de la endogamia en estos municipios, justifica la frecuencia de esta dolencia en la provincia Holguín. Al realizar estudios posteriores, la caracterización clínica y molecular con un diagnóstico precoz, nos permite detectar posibles individuos heterocigotos, para un adecuado asesoramiento genético a las familias en riesgo. En el municipio Holguín, el sexo masculino mostró mayor número de afectados en la quinta década de vida.

Introduction: Usher syndrome is a genetic disease. Nowadays, is the second visual and hearing impairment in the world. Among population from Holguín, Cuba, prevails a high autosomal recessive inheritance pattern, characterized by moderate to profound bilateral sensorineural hearing loss, progressive retinitis pigmentosa, and dysfunction, in some cases. Objective: to determine epidemiological behavior of Usher syndrome in Holguin, Cuba. Method: a retrospective descriptive study was conducted. Universe was formed by 53 patients with a clinical diagnosis of Usher syndrome. Variables studied were: sex, age, affected families, consanguineous marriages and municipality. Results: 60.4% of cases were males, with 30.2% between 50 and 59 years old. The municipalities of Holguín and Mayarí were the most affected, with 23% and 21% of consanguineous marriages each. Conclusions: a greater number of affected people were males in their fifties, from Holguín municipality. Inbreeding social practice in these areas shows the increasing frequency of this disease in Holguín province. Clinical and molecular characterization studies will allow an early diagnosis, detection of possible heterozygous individuals and provide adequate genetic counseling to families at risk.

Genetic analysis of a family with Usher syndrome / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To analyze the clinical features of a Usher syndrome family and explore the pathogenic gene of the disease. <p>METHODS: A Chinese family with Usher syndrome was involved in our study. After informed consent, careful clinical examinations were taken and 4mL blood were obtained. The whole genome DNA was extracted and target-captured next generation sequencing of the proband was performed to identify suspected mutations. We used Sanger sequencing to verify the detected mutations in all the members of the family, as well as in 100 normal controls. <p>RESULTS: In addition to typical retinitis pigmentosa, the patients suffered from mild to moderate sensorineural deafness. Sequencing results revealed compound heterozygous mutations(c.2310_2311insA and c.8559-2A>G)of <i>USH2A</i> gene in the patients, and either of the mutations was found in normal relatives that had consanguinity with the patients. Both of the mutations were not found in other members of the family and normal individuals. <p>CONCLUSION: <i>USH2A</i> is the pathogenic gene of the disease in this family. The mutation c.8559-2A>G(IVS42)is a previously reported mutation, while the mutation c.2310_2311 insA(p.E771Rfs*8)is a novel mutation. The study has expanded the mutation spectrum of <i>USH2A</i> gene resulting in Usher syndrome.

Estrategia comunitaria de prevención primaria y diagnóstico precoz del síndrome Usher en la provincia Holguín / Community Strategy of Primary Prevention and Early Diagnosis of Usher Syndrome in Holguin Province

Introducción: el síndrome Usher es una enfermedad determinada genéticamente, con una gran heterogeneidad clínica y genética, está caracterizada por hipoacusia neurosensorial de moderada a severa, retinosis pigmentaria progresiva y puede acompañarse de alteraciones en la función vestibular. Por su alta prevalencia en Holguín y su significativa discapacidad visual y auditiva, se hace necesario un instrumento preventivo y de diagnóstico. Objetivos: proponer una estrategia comunitaria de prevención primaria en estas familias y de diagnóstico precoz de esta afección genética, caracterizar evolutiva y clínicamente a todos los afectados. Métodos: se realizó un estudio descriptivo, tipo serie de casos a 53 pacientes con diagnóstico clínico de síndrome Usher, que son atendidos en Centro Provincial de Retinosis Pigmentaria de la provincia Holguín, en el periodo del febrero de 2009 a diciembre de 2015. Se revisaron las historias clínicas, recogiendo en un instrumento diseñado para el estudio todos los datos de interés, que permitió caracterizar el universo de estudio y determinar las variables susceptibles de análisis. Resultados: se logró caracterizar clínicamente el 100% de los enfermos estudiados. El 80% presentó la retinosis pigmentaria en la primera infancia. De estos, 33 afectados se encuentran en familias consanguíneas para el 62,26%, el número de familias consanguíneas fue de 17 para el 44,73% y las no consanguíneas 21 para el 55,26%. Conclusiones: se propone esta estrategia comunitaria que ayudará en la atención primaria a realizar prevención primaria en familias de afectados y diagnóstico precoz a los afectados lo cual permitió brindar un adecuado asesoramiento genético a estas familias.

Introduction: Usher syndrome is a genetically determined disease with great clinical and genetic heterogeneity. It is characterized by sensorineural hearing loss from mild to severe, progressive retinitis pigmentosa and may be accompanied by alterations in the vestibular function. Because of its high prevalence in Holguin and significant visual and hearing impairment, a preventive and diagnostic tool is necessary. Objective: propose a Community strategy for primary prevention in these families and early diagnosis of this genetic condition. Characterize all clinically affected and describe the evolutionary characteristics. Method: a series of cases descriptive study was carried out in 53 patients with a clinical diagnosis of Usher Syndrome, who are treated at the Provincial Center for Pigmentary Retinosis of Holguín province from February 2009 to December 2015. Clinical records, collecting in an instrument designed for the study all the data of interest that allowed to characterize the universe of study and to determine the variables susceptible of analysis. Results: clinical characterization of 100% of the patients studied was achieved. 80% had retinitis pigmentosa in early childhood. Of them, 33 affected patients are involved in consanguineous families for 62.26%, there were 17 consanguineous families for 44.73% and outbred 21 for a 55.26%. Conclusions: this community strategy that will help in primary care to undertake primary prevention in families of patients and early diagnosis allowing those affected to provide appropriate genetic counseling to these families is proposed.

Caracterización clínica del síndrome de Usher. Provincia Holguín / Usher syndrome clinical characterization. Holguin province

Fundamento: El síndrome de Usher es una enfermedad determinada genéticamente, con una gran heterogeneidad clínica y genética; está caracterizada por hipoacusia neurosensorial de moderada a severa, retinosis pigmentaria progresiva y puede acompañarse de alteración vestibular. Por la alta prevalencia de esta enfermedad en la provincia de Holguín, se considera necesario este estudio. Objetivo: Caracterizar clínicamente todos los enfermos con diagnóstico clínico de síndrome de Usher en la provincia Holguín, en el período de enero del 2009 a enero del 2016. Metodología: Se realizó un estudio descriptivo, retrospectivo, tipo serie de casos, a los 53 pacientes con diagnóstico clínico de síndrome de Usher en la provincia Holguín. La muestra estuvo formada por los 53 enfermos residentes en la provincia. Se revisaron los registros del Centro Provincial de Retinosis Pigmentaria y las historias clínicas de estos pacientes; se recogieron los datos de interés en un instrumento que se confeccionó para ello. Las variables estudiadas fueron el sexo, la edad, edad del diagnóstico de la hipoacusia y severidad, edad del diagnóstico de la retinosis pigmentaria y los resultados de las pruebas audiológicas, lo que permitió conocer la función vestibular. Resultados: Se caracterizó clínicamente el 100 % de los enfermos estudiados. Predominó el sexo masculino (60,37 %). El 80 % presentó la retinosis pigmentaria en la primera infancia y la hipoacusia congénita profunda en 67,92 %. Las pruebas vestibulares demostraron que el 71,70 % presenta síndrome de Usher tipo II y el 28,30 % tiene el tipo I. Conclusiones: Predominó el sexo masculino, la hipoacusia precedió a la alteración visual. Se logró caracterizar clínicamente a estos afectados. Prevaleció el síndrome de Usher tipo II.

Background: Usher syndrome is a genetically determined disease with great clinical and genetic heterogeneity. This disease is characterized by sensorineural hearing loss of moderate to severe, progressive pigmentosa retinitis and may be accompanied by vestibular alteration. At the high prevalence of this disease in the province of Holguin, this study is considered necessary. Objective: To characterize all patients clinically with clinical diagnosis of Usher syndrome in Holguin province, in the period from January 2009 to January 2016. Methodology: A series types of retrospective cases, descriptive study with 53 patients with clinical diagnosis of Usher syndrome in Holguin province was conducted. The sample consisted of 53 patients residing in the province. Provincial records Pigmentosa Retinitis Pigmentosa Center and the medical records of these patients were reviewed, the data of interest are collected in an instrument that was drawn up for these. The variables studied were sex, age, age at diagnosis of hearing loss and severity, age of diagnosis of pigmentosa retinitis and the results of the audiological tests, allowing knowing the vestibular function. Results: It was possible to clinically characterize 100 % of the patients studied, predominantly male in a 60.37 %. 80 % had pigmentosa retinitis in early childhood and profound congenital hearing loss in 67.92 %. Vestibular tests showed that 71. 70 % have Usher syndrome type II and 28.30 % have the type I. Conclusions: mainly males, hearing loss preceded visual impairment. It was possible to clinically characterize those affected. It prevailed Usher syndrome type II.

Pénfigo foliáceo variedad seborreica: reporte de un caso / Pemphigus foliaceus seborrheic variety: a case report / Pénfigo foliáceo variedade seborreica: relato de caso

El pénfigo eritematoso o seborréico, también denominado síndrome de Senear-Usher es la variedad leve y localizada del pénfigo foliáceo, de baja incidencia. La mayor parte de los casos se han reportado en adultos entre la segunda y tercera década de la vida, promedio de 54 años, sin predominio entre razas o sexo. Su etiología se debe a la presencia de anticuerpos anti IgG contra la desmogleina 1 de los queratinocitos de la capa granulosa. Clínicamente se presenta en forma de placas eritematoescamosas o eritematocostrosas bien definidas, de aspecto y distribución seborreica (cara, cuello y tronco), que se exacerban a la exposición solar. Su diagnóstico clínico puede ser difícil, ya que se superpone clínicamente con el lupus eritematoso discoide y la dermatitis seborreica, por lo cual es importante tenerlo en cuenta como diagnóstico diferencial en lesiones infiltradas en dorso nasal y región malar en patrón de alas de mariposa. Se presenta el caso clínico de un paciente con pénfigo foliáceo variedad seborreica una entidad de baja incidencia.

Pemphigus erythematosus or seborrheic, also called Senear - Usher syndrome,is a mild, localized variety of pemphigus foliaceus, an entity of low incidence. Most cases have been reported in adults between second and third decades of life, average 54 years, no difference between race or sex. Etiology is due to the presence of IgG antibodies against desmoglein 1 in keratinocytes of the granular layer. Clinically, defined erythematous plaques, seborrheic distribution aspect (face, neck and trunk), which are exacerbated by sun exposure. Clinical diagnosis can be difficult as clinically overlaps with discoid lupus erythematosus and seborrheic dermatitis. So, it is important to be considered as differential diagnosis in infiltrated nasal lesions, dorsum and malar region butterfly pattern. We report a case of pemphigus foliaceus- seborrheic variety, a low incidence entity.

O pênfigo eritematoso do tipo seborréico, também chamada de síndrome Senear -Usher é variedade leve e localizada do pênfigo foliáceo , de baixa incidência , a maioria dos casos foram relatados em adultos entre a segunda e terceira década de vida , com idade media de 54 anos, sem predominância entre raças ou sexo. A sua etiologia é devido à presença de anticorpos anti - IgG de desmogleína 1 dos queratinócitos da camada granular . Clinicamente, apresenta-se como placas eritematosas ou eritematocostrosas bem definidos, de aspecto e distribuição seborreica (face, pescoço e tronco), que são agravadas pela exposição ao sol. Seu diagnóstico clínico pode ser difícil, pois se sobrepõe clinicamente com lúpus eritematoso discóide e dermatite seborreica, por isso é importante te-lo em mente como diagnóstico diferencial nas lesões infiltradas no dorso da nariz e região malar com asas de borboleta. Apresenta-se o caso de um paciente com pênfigo foliáceo do tipo seborreico uma entidade de baixa incidência com poucos casos relatados na literatura.

A Novel Frameshift Mutation of the USH2A Gene in a Korean Patient with Usher Syndrome Type II

Usher syndrome type II (USH2) is the most common form of Usher syndrome, characterized by moderate to severe hearing impairment and progressive visual loss due to retinitis pigmentosa. It has been shown that mutations in the USH2A gene are responsible for USH2. The authors herein describe a 34-year-old Korean woman with the typical clinical manifestation of USH2; she had bilateral hearing disturbance and progressive visual deterioration, without vestibular dysfunction. Molecular genetic study of the USH2A gene revealed a novel frameshift mutation (c.2310delA; Glu771LysfsX17). She was heterozygous for this mutation, and no other mutation was found in USH2A, suggesting the possibility of an intronic or large genomic rearrangement mutation. To the best of our knowledge, this is the first report of a genetically confirmed case of USH2 in Korea. More investigations are needed to delineate genotype-phenotype correlations and ethnicity-specific genetic background of Usher syndrome.

USH2A gene mutations spectrum in Chinese different from Westerner / 中华实验眼科杂志

Usher syndrome (USH) is the most common syndromic retinitis pigmentosa (RP),which is an autosomal recessive disorder.RP is highly clinically and genetically heterogeneous.A total of 12 loci including nine genes have been identifiedas causing various clinical subtypes of USH.The USH2A gene is thought to be involved in the pathogenesis of most USH2 cases.Moreover,mutations of the USH2A gene is also responsible for atypical USH and nonsyndromic retinitis pigmentosa.Some studies found that the mutation spectrum among Chinese RP patients might differ from European Caucasians.Herein,the further survey should be performed to ascertain the hot gene mutation spectrum.

A Case of Type 2 Usher Syndrome / 대한이비인후과학회지

The Usher syndrome is an autosomal recessive disorder that cause bilateral sensorineural hearing loss and progressive loss of vision. It is genetically heterogeneous and is the most frequent cause of hereditary deafness and blindness in human. There are three types of Usher syndrome that can be distinguished clinically and into different subtypes. Type 2 Usher syndrome is the most common form and less severe than Type 1. It is characterized by congenital, moderate to severe, high frequency sloping hearing loss, retinitis pigmentosa which is typically diagnosed in late adolescence, and normal vestibular function. Recently, we have experienced a case of clinically diagnosed Type 2 Usher syndrome in a 34 years old female. We report this case with a brief review of literature. This is the first Type 2 Usher Syndrome to be reported in the otolaryngologic field in Korea.

The Clinical Manifestations of Usher Syndrome in Korea

PURPOSE: To obtain useful information for counseling patients with Usher syndrome by analyzing the characteristics of its ophthalmologic manifestations. METHOD: The records of eight patients were reviewed for visual acuity, refractive error, Goldmann perimetry, electroretinogram, and other abnormalities. RESULTS: The best corrected visual acuity was 20/30 or better, bilaterally in six patients. All patients showed retinal findings characteristic of of retinitis pigmentosa. All seven patients who received Goldmann perimetry showed visual field defect. Furthermore, electroretinograms taken from seven patients were all extinguished. Six patients had myopic astigmatism, with one showing high myopia. Two patients showed exotropia. No correlation was found between the severity of the ophthalmologic problems and the level of the hearing loss or vestibular dysfunction. CONCLUSIONS: Visual acuity was relatively preserved in most patients. Usher syndrome can be accompanied by strabismus, myopia, and even high myopia.

A Case of Usher Syndrome / 대한이비인후과학회지

The usher syndrome (US) is an autosomal recessive disorder characterized by congenital bilateral sensorineural hearing loss and progressive visual loss secondary to retinitis pigmentosa. It is the most common cause of the hereditary combined deafness-blindness in the western world. Three different types of US are recognized by clinical criteria. The US type I has severe to profound hearing loss, vestibular dysfunction, and prepubertally diagnosed retinitis pigmentosa, while the US type II has moderate to severe hearing loss, normal vestibular function, and later onset of retinitis pigmentosa. The US type III has a progressive hearing loss and retinitis pigmentosa with variable vestibular involvement. The diagnosis is confirmed by medical history and thorough otoscopical, audiologic, vestibular, and ophthalmological examinations. We have recently experienced a case of the US type I and report this with a brief review of the related literature.

Características clínicas y genéticas del Síndrome de Usher / Clinical Characteristics of the Usher's syndrome

Con el objetivo de describir las características clínicas y genéticas del síndrome de Usher, se realizó un estudio descriptivo transversal en el Centro de Retinosis Pigmentaria de Camagüey, desde octubre de 1991 hasta Mayo de 1998, con siete pacientes con síndrome Usher. A través de entrevistas y confección de encuestas, incluyendo el árbol genealógico se recopilaron los datos necesarios; los cuales fueron procesados realizándose estadística descriptiva. El síndrome de Usher tipo II fue el más frecuente. El inicio de la hipoacusia y de las manifestaciones oftalmológicas más frecuentes fueron la ceguera nocturna y la fotofobia. Hubo consanguinidad en el 28, 57 % de las familias y los antecedentes patológicos se presentaron en tres familias (43%). La enfermedad es clínica y genéticamente heterogénea. Debe ser sospechada en todo paciente con retinosis pigmentaria e hipoacusia. El diagnóstico debe realizarse precozmente.

State the clinical and genetic characteristics of the Usher syndrome, a descriptive and transversal study was carried out at the Camagüey retinosis pigmentaria Center, since octuber 1991 until may 1998 with seven patients affected by Usher syndrome. By interviews and preparation of surveys, including the genealogical tree necessary data were collected. Esher syndrome type II was the most frequent. Hearing loss and ocular manifestations onset were variable. Nigth blindness and phoptofobia were to the more frequent of the ophptalmologic manifestations. Consaguinity within families and pathological antecedents were found in 28, 57% and 43% respectively. The disease is clinical and genetically heterogenous. It must he suspected in all patients with retinitis pigmentosa and hearing loss. The diagnosis may be done early.

Genetic Counselling in a Case of Usher Syndrome Type III.

Usher Syndrome is a recessive disease characterised by dual sensory impairment. We report a case of Usher Syndrome, probably of Type III, characterised by post-lingual progressive sensorineural hearing loss and retinitis pigmentosa who sought genetic counselling.

Localisation Of The Usher Syndrome Type I Gene In The French Acadian Population Of Louisiana To Chromosome 11p14-p15.1 By Linkage and Haplotype Analysis.

The Usher syndromes (USH) are autosomal recessive diseases characterised by congenital sensorineural hearing loss and progressive pigmentary retinopathy with or without vestibular dysfunction. At least three distinct loci causing type 1 Usher syndrome (USH1) have been reported, with the USHl locus found in the French-Acadian families of Louisiana (USHlC) mapping to chromosome 11p. In this study 16 microsatellite markers were used to refine the position of the USH1 locus in the French-Acadian population of Louisiana. Two-point linkage analysis showed no recombination between US1C and D11S419 (Zmax = 2.95), D11S902 (Zmax = 6.44), D11S921 (Zmax = 3.31), and D11S899 (Zmax = 5,46). A map of chromosome 11p14-15.1 based on microsatellite markers was developed for use in mapping USH1C. Multipoint linkage analysis gave Z = 6.5 at D11S899 with a one-lod confidence interval covering 5 cM interval. The closest flanking markers showing obligate recombinants are D11S861 and D11S928, which localises USH1C to a 9 cM interval. However, examination of the marker haplotypes in individuals affected by USH1C is consistent with the suggestion that the high icnidence of USH1 in this population is the result of a founder effect and places the USH1C locus in the 5cM interval bounded by D11S861 and D11S899.

Two Cases Usher's Syndrom in two Brothers

Usher's syndrome is an autosomal recessively inherited trait that characterized by a congenital nonprogressive sensorineural hearing impairment and progressive night-blinding disorder, retinitis pigmentosa, with cataract, psych psis, speech disorder, mental deficiency, and vestibular ataxia being variable additional findings. We experienced two cases of Usher's syndrome in two brothers, which has the hearing loss and night-blinding disorder that had been developed since in early childhood and 2nd decade respectively. Their ophthalmoscopic retinal and ERG findings are characteritic ones of retinitis pigmentosa. such as 1) bone corpuscle pigmentation in the periphery, narrow arteries, and a waxy, yellowish optic, disc, 2) non-recordable ERG, respectively. Their pure tone automatry confirmed the bilateral sensorineural hearing loss.