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W Kimberling

Publications and source records attributed to W Kimberling.

At least 19 recordsLinked to original sources
PubMed2000

Histopathologic features of the temporal bone in usher syndrome type I.

Temporal bones of 2 patients with Usher syndrome type I were examined using light microscopy. In both patients, findings from histopathologic examination of the cochlea were characterized by degeneration of the organ of Corti, which was most marked in the basal turn, atrophy of the stria vascularis, and a decrease in the number of spiral ganglion cells. The cochlear nerve appeared to be diminished. The sensory epithelium of the saccular and utricular maculae of patient 1 was normal for age. The left temporal bone of patient 2, classified as Usher syndrome genetic subtype USH1D or USH1F, demonstrated the typical signs of severe cochleosaccular degeneration. Present cases and cases from the literature were reviewed in search of an explanation for the above-described differences in histologic findings.

Aged↗
PubMed1999

The cochlear nuclei in two patients with Usher syndrome type I.

HYPOTHESIS: Does long-term sound deprivation lead to degeneration of the cochlear nuclei in two Usher type I patients? METHODS: The cochlear nuclei of these patients were morphometrically analyzed and compared with two age-matched controls. Routine autopsy of the brainstems was performed before the design of this study was known. During this procedure, the ventral cochlear nucleus (VCN) can easily be damaged. Five partially damaged VCN could nevertheless be analyzed for this study, including the right VCN of Usher patient 1 and both VCN of Usher patient 2. Using 15 microm thick serial paraffine sections of the cochlear nuclei, estimates of volume, neuronal densities, number of cells and mean cell diameter of the dorsal cochlear nucleus (DCN) and VCN were obtained. RESULTS: This study presents unique material of the cochlear nuclei in two patients with Usher syndrome type I. Data regarding volume and total cell number of the VCN are influenced by the absence of a part of the VCN. Results suggest a decrease in mean cell diameter of the VCN in Usher patients. Other parameters of the VCN and DCN, however, showed no major differences between Usher type I patients and controls. CONCLUSION: Only minor degenerative changes are apparent in the cochlear nuclei of two patients with Usher type I, who were deprived of acoustic stimuli since birth.

Aged↗
PubMed1999

Hearing impairment related to age in Usher syndrome types 1B and 2A.

OBJECTIVE: To evaluate hearing impairment in 2 common genetic subtypes of Usher syndrome, USH1B and USH2A. DESIGN: Cross-sectional analysis of hearing threshold related to age in patients with genotypes determined by linkage and mutation analysis. SETTING: Otolaryngology department, university referral center. PATIENTS: Nineteen patients with USH1B and 27 with USH2A were examined. All participants were living in the Netherlands and Belgium. MAIN OUTCOME MEASURE: Pure tone audiometry of the best ear at last visit. RESULTS: The patients with USH1B had residual hearing without age dependence, with minimum thresholds of 80, 95, and 120 dB at 0.25, 0.5, and 1 to 2 kHz, respectively. Mean thresholds of patients with USH2A were about 45 to 55 dB better than these minimum values. Distinctive audiographic features of patients with USH2A were maximum hearing thresholds of 70, 80, and 100 dB at 0.25, 0.5, and 1 kHz, respectively, only at younger than 40 years. Progression of hearing impairment in USH2A was 0.7 dB/y on average for 0.25 to 4 kHz and could not be explained by presbyacusis alone. CONCLUSIONS: The USH1B and USH2A can be easily distinguished by hearing impairment at younger than 40 years at the low frequencies. Hearing impairment in our patients with USH2A could be characterized as progressive.

Adult↗
PubMed1999

Mutation detection of PKD1 identifies a novel mutation common to three families with aneurysms and/or very-early-onset disease.

It is known that several of the most severe complications of autosomal-dominant polycystic kidney disease, such as intracranial aneurysms, cluster in families. There have been no studies reported to date, however, that have attempted to correlate severely affected pedigrees with a particular genotype. Until recently, in fact, mutation detection for most of the PKD1 gene was virtually impossible because of the presence of several highly homologous loci also located on chromosome 16. In this report we describe a cluster of 4 bp in exon 15 that are unique to PKD1. Forward and reverse PKD1-specific primers were designed in this location to amplify regions of the gene from exons 11-21 by use of long-range PCR. The two templates described were used to analyze 35 pedigrees selected for study because they included individuals with either intracranial aneurysms and/or very-early-onset disease. We identified eight novel truncating mutations, two missense mutations not found in a panel of controls, and several informative polymorphisms. Many of the polymorphisms were also present in the homologous loci, supporting the idea that they may serve as a reservoir for genetic variability in the PKD1 gene. Surprisingly, we found that three independently ascertained pedigrees had an identical 2-bp deletion in exon 15. This raises the possibility that particular genotypes may be associated with more-severe disease.

Adult↗
PubMed1997

An introduction to the genetics of normal and defective hearing.

The recent rapid development of molecular biology techniques applied to the genetics of normal and defective hearing shed a new light on old questions regarding hearing and deafness. Genes are DNA sequences that determine characteristics, normally by specifying the sequence of aminoacids in a protein. The majority of genes is located in the chromosomes (human chromosomes have perhaps 80,000 pairs of genes). In addition there are 37 mithochondrial genes which are inherited only from the mother. One method used to identify candidate genes based on their function or pattern of tissue expression involves the construction of cDNA libraries from the target organ or tissue, in this case from the cochlea. The construction and characterization of cochlear cDNA libraries from humans and other species provide an important resource for rapid identification of cochlear genes involved in normal hearing and hearing disorders. Studies of the molecular genetics of the inner ear are hampered by the relative inaccessibility of the cochlea, by the limited number of cochlear and vestibular cells, and by our inability to maintain many of these cell types in long-term cultures. Several rodent inner-ear cDNA libraries and a human foetal cochlear cDNA library have already been constructed. Human and rodent cochlea-subtracted cDNA libraries are very useful for identifying genes controlling the development and maintenance of hearing. cDNA libraries constructed at different stages of development, and subtracted from each other, could be instrumental in identifying genes important at each stage of cochlear development. In addition, these libraries have the potential of fostering the identification of other proteins unique to the cochlea and will contribute to the identification, characterization, and functional analysis of these cochlea-specific proteins. Another important application of cDNA libraries is in identifying hearing-loss genes. Once the candidate gene for a given type of hearing loss is cloned and decoded, the structure of its protein product can be determined. This will provide insights into the biochemical function of the gene product in normal cochlear tissue, and will show why the genetic mutation results in hearing loss, that is, the recent identification of the myosin VIIa gene in Usher type IB. In addition, through the use of homologous recombination and transgenic technology, in vivo mouse models of inner-ear genetic disorders can be created. To date, 350 different genetic conditions associated with hearing impairment have been described, and during the past five years several of the genes involved in these form have already been mapped and identified.

Animals↗
PubMed1997

Linkage of a gene causing high bone mass to human chromosome 11 (11q12-13)

The purpose of this paper is to report the linkage of a genetic locus (designated "HBM") in the human genome to a phenotype of very high spinal bone density, using a single extended pedigree. We measured spinal bone-mineral density, spinal Z(BMD), and collected blood from 22 members of this kindred. DNA was genotyped on an Applied Biosystems model 377 (ABI PRISM Linkage Mapping Sets; Perkin Elmer Applied Biosystems), by use of fluorescence-based marker sets that included 345 markers. Both two-point and multipoint linkage analyses were performed, by use of affected/unaffected and quantitative-trait models. Spinal Z(BMD) for affected individuals (N = 12) of the kindred was 5.54 +/- 1.40; and for unaffected individuals (N = 16) it was 0.41 +/- 0.81. The trait was present in affected individuals 18-86 years of age, suggesting that HBM influences peak bone mass. The only region of linkage was to a series of markers on chromosome 11 (11q12-13). The highest LOD score (5.21) obtained in two-point analysis, when a quantitative-trait model was used, was at D11S987. Multipoint analysis using a quantitative-trait model confirmed the linkage, with a LOD score of 5.74 near marker D11S987. HBM demonstrates the utility of spinal Z(BMD) as a quantitative bone phenotype that can be used for linkage analysis. Osteoporosis pseudoglioma syndrome also has been mapped to this region of chromosome 11. Identification of the causal gene for both traits will be required for determination of whether a single gene with different alleles that determine a wide range of peak bone densities exists in this region.

Absorptiometry, Photon↗
PubMed1995

Clinical findings in obligate carriers of type I Usher syndrome.

Seventeen obligate carriers from nine families with autosomal recessive Usher syndrome type I underwent otological, audiological, vestibular, and ophthalmological examination in order to identify possible manifestations of heterozygosity. Linkage studies were performed and six families showed linkage to chromosome region 11q13.5 while 3 families have so far failed to show linkage to the candidate regions. Eight obligate carriers had an abnormal pure-tone audiogram. Two different audiometric patterns could be distinguished when hearing loss was corrected for age and sex. Four carriers (24%) had significant sensorineural hearing loss (SNHL) which increased at higher frequencies. The other 13 carriers had SNHL of about 10 dB at 0.25 and 0.5 kHz, but less at higher frequencies. Vestibular findings were generally normal. Electro-oculography demonstrated a significant lower mean light peak/dark trough ratio in Usher type I carriers compared to normal control individuals. The methods used in this study were found not to be specific enough to clinically identify carriers of Usher type I syndrome. Nevertheless it is remarkable that a number of obligate carriers showed significant audiological and ophthalmological abnormalities.

Adult↗
PubMed1994

Autosomal dominant polycystic kidney disease in blacks: clinical course and effects of sickle-cell hemoglobin.

Autosomal dominant polycystic kidney disease (ADPKD) is a frequent cause of ESRD, but its frequency in blacks has not been well delineated and its course and the effects of sickle hemoglobin in this disease in blacks have not been previously reported. The occurrence of ADPKD in blacks and whites was determined in two ESRD populations: all ESRD patients seen over a 16-yr period in one area of Southeast Tennessee and all ESRD patients in 15 hemodialysis units in Tennessee and Atlanta, GA. The frequency of sickle hemoglobin was determined and compared in a group of nonrelated blacks with ESRD with and without ADPKD. The age at onset of ESRD and factors that might affect ADPKD such as gender, hypertension, and hemoglobin type were examined. ADPKD was a less frequent cause of ESRD in blacks than whites (1.4 versus 6.8%). However, after adjusting for the population rate, the incidence rates in blacks and whites were similar (0.48 and 0.47 of 100,000). There was a higher incidence of sickle hemoglobin in nonrelated blacks with ADPKD versus other black ESRD patients (50 versus 7.5%; P < 0.005). Blacks had an earlier onset of ESRD than whites (43.2 versus 55.4 yr; P < 0.0001), as did blacks with sickle-cell trait versus blacks without (38.2 versus 48.1 yr; P < 0.003). In this population, hypertension and gender had no effect on the onset of ESRD. ADPKD accounted for a smaller percentage of blacks than whites with ESRD because of the high percentage of blacks with renal disease from other causes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The distorted alpha 2-adrenoceptor genotype distribution in F2 populations of Dahl salt sensitive and resistant rats cross.

To examine the role of the alpha 2-adrenoceptor gene in the development of genetic hypertensive rats, we tested Dahl salt sensitive (S) and resistant rats (R) for the presence of a restriction fragment length polymorphism (RFLP) in that gene. An RFLP was found between the S and R rats with a human kidney cDNA alpha 2-adrenoceptor probe (alpha 2-C4) and Msp I restriction endonuclease. The alpha 2-C4 probe detected two alleles, S and R, of 3.0 and 2.8 kb in size. The two strains of rats were each homozygous for their corresponding allele. The inheritance of the alleles was investigated by crossbreeding S and R rats and subsequent brother/sister mating of F1 rats. Two hundred and fifteen F2 rats were produced by breeding 14 pairs of F1 rats. An atypical distribution of alpha 2-adrenoceptor genotypes was observed. We found a reduced number of the SS genotype in both males and females of the F2 generation. To investigate the mechanism of this distorted alpha 2-adrenoceptor genotype distribution in the F2 rats of S and R cross, we backcrossed the F1 rats to their S and R parents. The litter size and gender distribution were counted for each breeding colony. Analysis by chi-square test showed that there was no sex difference among the backcrosses. Also, there was no significant decrease in litter size. This excludes the possibilities of fetal demise of S homozygotes and intrauterine selection. Therefore the deficiency of SS genotype may be due to gene recombination or may not be due to the alpha 2-adrenoceptor gene itself, but to the effect of other genes closely linked to the alpha 2-adrenoceptor.

Animals↗
PubMed1992

Clinical variability and genetic heterogeneity within the Acadian Usher population.

A number of Usher syndrome (USH) families are found among the French-Acadians living in southwestern Louisiana. These families are descended from a few common ancestors, suggesting that USH may be homogeneous within this ethnic group. However, we report distinct phenotypic variability. Based on differences in psychomotor development and tests of auditory and vestibular function, Acadian individuals with both USH Type 1 and Type 2 can be identified. One additional family, with unusual findings, represents a third clinical phenotype. Linkage data strongly support these clinical observations.

Blindness↗
PubMed1992

Gene mapping of the Usher syndromes.

USH is an autosomal recessive group of diseases characterized by auditory impairment and visual loss owing to RP. Two common types of USH are known, types I and II. USH type I is characterized by a congenital severe to profound hearing impairment, absent vestibular function, and a progressive pigmentary retinopathy. Persons with type I do not find hearing aids useful, have delayed motor development, and experience progressive night blindness and peripheral visual loss, which usually begins in their second decade. USH type II is characterized by a congenital moderate to severe hearing loss with a down-sloping audiogram, normal vestibular function, and a progressive pigmentary retinopathy. Persons with USH2 find hearing aids beneficial, have normal psychomotor development, and experience progressive night blindness and peripheral visual loss, which usually begins in their third decade. Vestibular dysfunction is the best distinguishing hallmark to differentiate USH type I from type II. One USH type II gene (called USH2) has been assigned to chromosome 1q. One USH type I gene has been tentatively assigned to chromosome 14q. There are other USH genes that have not yet been localized.

Chromosome Mapping↗
PubMed1988

Dyslexia subtypes: genetics, behavior, and brain imaging.

This study was designed to identify inherited subtypes of specific dyslexia and to characterize these types by a variety of studies. A previous linkage study in large three-generation families resulted in a LOD score of 3.24 at a 13% recombination frequency between dyslexia and normal variations for the short arm of chromosome 15. The odds for linkage with chromosome 15 markers are better than 1,000 to 1. We estimate that 30% of an extended series of families show linkage to chromosome 15 polymorphisms. Other linkages remain to be identified. PET scanning is being used to examine measures of regional cerebral glucose metabolism during two types of reading by (adult) dyslexics and normal readers. MRI is also being used to examine pertinent brain structures. Behavioral tests are also in progress. The long-term goals of this study are to develop specific genetic and other diagnostic techniques that can be used to test children before beginning school and to develop sufficient understanding of the abnormal brain function of each subtype so that specific and effective remedial programs can be developed.

Brain↗
PubMed1987

Familial colon cancer in the Tel-Aviv area and the influence of ethnic origin.

The family history of colon cancer was investigated in 38,823 individuals (2,129 families) who comprised a control and an oncology patient series from Tel-Aviv and nearby areas. A significant increased risk for colon cancer was observed among first-degree relatives of colon cancer patients when compared to controls. When the patient sample was divided into two groups based on country and continent of birth--European (Ashkenazim) and other (nonAshkenazim)--the relatives of the nonAshkenazi subjects showed a greater relative risk for colon cancer (P less than 0.05). Colon cancer was found to be less frequent in nonAshkenazim than in Ashkenazim controls. These findings suggest that although the colon cancer frequency in the nonAshkenazi group is lower, the genetic component may be more important than for the Ashkenazi sample. The nonAshkenazi Jews may represent distinct subgroups that differ with respect to either primary genetic susceptibility to colorectal cancer and/or they may have been subjected to peculiar, environmental carcinogenic exposures when compared to their Ashkenazim brethren.

Adult↗
PubMed1986

Segregation analysis of hereditary nonpolyposis colorectal cancer.

Segregation analysis of eleven families comprising 2762 individuals indicated compatibility of the data with segregation of a major autosomal dominant gene for hereditary nonpolyposis colorectal cancer. It was estimated that between 71% and 79% of the gene carriers were susceptible and had age of onset that was normally distributed with mean about 47 and standard deviation about 10 years. There was a low frequency of sporadic cases at the older ages, a little less than four percent of nongene carriers being affected by age 80. No significant differences were found between the families exhibiting endometrial cancer (cancer family syndrome) and those not exhibiting endometrial cancer (hereditary site-specific nonpolyposis colonic cancer).

Adult↗
PubMed1985

Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II). I. Clinical description of resource.

Hereditary nonpolyposis colorectal cancer (HNPCC) is comprised of the following: the cancer family syndrome (CFS), or Lynch syndrome II, which shows early-onset proximal colonic cancer predominance and other associated extracolonic adenocarcinomas, particularly endometrial carcinoma; and hereditary site-specific colon cancer (HSSCC), or Lynch syndrome I, which shows all of the same characteristics, except for extracolonic cancer. Nine families with CFS and two with HSSCC provided the resource that was tested for biomarkers (see companion article). All families were meticulously evaluated for genealogy and cancer verification. Biologic specimens were obtained during field visits to areas of closest geographic proximity to the families. Cancer education and recommendations for surveillance/management were provided to patients and their physicians. Additionally, 40 families (about 3000 individuals) with either CFS or HSSCC have been ascertained. Syndrome cancers were restricted to direct-line relatives as opposed to nonbloodline relatives, arguing against involvement of environmental factors. One documented clinical feature was a predilection for proximal versus distal colonic cancer in both CFS and HSSCC kindreds. This has important clinical significance in that it clarifies the need for instituting effective surveillance earlier to detect the predominantly proximal colonic cancers.

Adolescent↗
PubMed1984

Hypertrophic form of peroneal muscular atrophy (PMA): unusual nerve conduction results.

A family with a hypertrophic form of peroneal muscular atrophy (PMA) was studied with typical clinical and electrophysiological abnormalities in the propositus and her child. The propositus' father was asymptomatic and slowing of nerve conduction velocities was limited to the peroneal nerves. Actual parentage was confirmed by 22 different serologic and electrophoretic marker systems.

Adolescent↗
PubMed1978

Serum IgM in retinitis pigmentosa: a genetic study.

Because of a published report that serum immunoglobulin M (IgM) was elevated in some cases of retinitis pigmentosa (RP), a genetic study was undertaken to determine if a particular pattern of inheritance was associated with elevated IgM. Seventy-five RP patients in 37 families were ascertained and classified by pattern of inheritance into six groups. Serum IgM was quantitated by the radial immunodiffusion technique. Fifty-one controls were also studied. Methods of adjusting the IgM values for sex, age, and race were derived, but only a sex adjustment was used, since no effect of age on IgM was found in this sample, and there were few data on race. There was no signifcant difference in mean IgM levels between RP patients and controls. The variance of the RP group was slightly greater than that of the controls. One-way analysis of variance of the six genetic categories of RP and controls was performed on the raw data and on the data after log transformation. The F-ratio was not significant, indicating that there was no difference in serum IgM levels among the seven groups. Possible reasons for the discrepancy in results between this study and the previous report are presented.

Female↗