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1.
Urol Pract ; 9(5): 371-378, 2022 Sep.
Article in English | MEDLINE | ID: mdl-37145727

ABSTRACT

INTRODUCTION: There is a need to better understand the role of postoperative care via telemedicine (TM). We evaluated patient satisfaction and outcomes of postoperative face-to-face (F2F) versus TM visits for adult ambulatory urological surgeries in an urban academic center. Methods:This was a prospective, randomized controlled trial. At surgery, patients undergoing ambulatory endoscopic procedures or open surgery were randomized 1:1 to a postoperative F2F or TM visit. After the visit, a telephone survey assessing satisfaction was administered. Primary outcome was patient satisfaction; secondary outcomes were time and cost savings, and 30-day safety outcomes. Results:A total of 197 patients were approached; 165 (83%) consented and were randomized-76 (45%) to F2F and 89 (54%) to TM cohorts. There were no significant differences in baseline demographics between the cohorts. Both cohorts were equally satisfied with their postoperative visit (F2F 98.6% vs TM 94.1%, p=0.28) and found their visit to be an acceptable form of health care (F2F 100% vs TM 92.7%, p=0.06). The TM cohort saved a significant amount of time (TM 66.2% spent <15 minutes vs F2F 43.1% spent 1-2 hours, p <0.0001) and money (44.1% TM saved $5-$25 vs 43.1% F2F spent $5-$25, p=0.041) associated with travel. There were no significant differences in 30-day safety outcomes between the cohorts. Conclusions:TM for postoperative visits after ambulatory adult urological surgery saves patients time and money without compromising satisfaction or safety. TM should be offered as an alternative to F2F for routine postoperative care for certain ambulatory urological surgeries.

2.
Urology ; 153: 156-163, 2021 07.
Article in English | MEDLINE | ID: mdl-33497720

ABSTRACT

OBJECTIVE: To assess prescribing and refilling trends of narcotics in postoperative urology patients at our institution. Although the opioid epidemic remains a public health threat, no series has assessed prescribing patterns across urologic surgery disciplines following discharge. METHODS: All urologic surgeries were retrospectively reviewed from May 2017-April 2018. Demographics, comorbidities, and postoperative pain management strategies were analyzed. Narcotics usage following surgery were reported in total morphine equivalents (TME). Opioid refill rate was characterized by medical specialty and stratified by urologic discipline. RESULTS: 817 cases were reviewed. Mean age and TME at discharge was 57±15.6 years and 35.43±19.5 mg, respectively. 13.6% (mean age 55±15.9) received a narcotic refill following discharge (mean TME/refill 37.7±28.9 mg). A higher proportion of patients with a pre-operative opioid prescription received a refill compared to opioid naïve patients (38.2% vs 21.6%, P < .01). Refill rate did not differ between urologic subspecialties (P = .3). Urologists were only responsible for 20.4% of all refills filled, despite all patients continuing follow-up with their surgeon. Procedures with the highest rates of post-operative refills were in oncology, male reconstruction/trauma and endourology. Patients with a history of chronic pain (OR 1.9, CI 1.1-3.3) preoperative narcotic prescription (OR 1.6, CI 1.0-2.6), and higher ASA score (OR 1.8, CI 1.6-2.8) were more likely to obtain a postoperative opioid prescription refill. CONCLUSION: Approximately 1 in 7 postoperative urology patients receive a postoperative narcotics refill; however, nearly two-thirds receive refills exclusively from non-urologic providers. Attempts to avoid overprescribing of postoperative narcotics need to account for both surgeon and nonsurgeon sources of opioid refills.


Subject(s)
Analgesics, Opioid/administration & dosage , Pain Management , Pain, Postoperative , Urologic Surgical Procedures/adverse effects , Female , Health Personnel/classification , Health Personnel/statistics & numerical data , Humans , Male , Middle Aged , Needs Assessment , Pain Management/methods , Pain Management/standards , Pain Management/statistics & numerical data , Pain, Postoperative/diagnosis , Pain, Postoperative/drug therapy , Pain, Postoperative/epidemiology , Pain, Postoperative/etiology , Patient Discharge/statistics & numerical data , Practice Patterns, Physicians'/standards , Quality Improvement/organization & administration , United States/epidemiology , Urologic Surgical Procedures/methods , Urologic Surgical Procedures/statistics & numerical data
3.
J Urol ; 197(4): 1092-1098, 2017 04.
Article in English | MEDLINE | ID: mdl-27866958

ABSTRACT

PURPOSE: There is controversy regarding the performance of concomitant anti-incontinence procedures at the time of pelvic organ prolapse repair. Data support improvement in stress urinary incontinence with a concomitant sling but increased adverse events. We assessed trends in preoperative stress urinary incontinence evaluation, concomitant anti-incontinence procedure at pelvic organ prolapse surgery and postoperative anti-incontinence procedures at our institution before and after the 2011 FDA (U.S. Food and Drug Administration) Public Health Notification pertaining to vaginal mesh. MATERIALS AND METHODS: We retrospectively reviewed the records of patients who underwent pelvic organ prolapse surgery from 2009 to 2015. Preoperative workup included assessment of subjective stress urinary incontinence and/or evaluation for leakage with reduction of pelvic organ prolapse on physical examination, urodynamics or a pessary trial. The percentages of concomitant and postoperative anti-incontinence procedures were compared before and after the 2011 FDA notification. RESULTS: A total of 775 women underwent pelvic organ prolapse repair. The percentage of anti-incontinence procedures at pelvic organ prolapse repair decreased from 54.8% to 38.0% after the FDA notification (p = 0.002) while the incidence of preoperative objective stress urinary incontinence on examination, urodynamics and pessary trials remained constant. The incidence of postoperative anti-incontinence procedures within 1 year of the index surgery remained low. CONCLUSIONS: We found a decrease in the incidence of concomitant anti-incontinence procedures at the time of pelvic organ prolapse repair following the 2011 FDA notification despite no significant decline in subjective stress urinary incontinence or demonstrable stress urinary incontinence on preoperative evaluation. Further analysis is warranted to assess the impact of the FDA notification on treatment patterns in women with pelvic organ prolapse and stress urinary incontinence.


Subject(s)
Pelvic Organ Prolapse/surgery , Urinary Incontinence, Stress/surgery , Female , Humans , Middle Aged , Pelvic Organ Prolapse/complications , Postoperative Complications/etiology , Procedures and Techniques Utilization/statistics & numerical data , Retrospective Studies , Surgical Mesh/adverse effects , Urinary Incontinence, Stress/complications , Urologic Surgical Procedures/methods
4.
J Endourol ; 30(9): 970-4, 2016 09.
Article in English | MEDLINE | ID: mdl-27301268

ABSTRACT

PURPOSE: Primary ureteroscopic intervention for kidney or ureteral stones occasionally encounters difficulty with passage of the ureteroscope in the initial procedure. These patients require a second procedure after stenting. We aim to define the contemporary failure rate of primary ureteroscopy (URS) and identify predictive factors that necessitate prestenting. This will assist in preoperative patient counseling, informed consent, and clinical decision-making. MATERIALS AND METHODS: We conducted a multi-institutional retrospective review of 535 unstented patients undergoing primary URS from August 2011 to August 2013. The primary outcome was gaining access to the unstented ureter. RESULTS: The failure rate for accessing the unstented ureter was 7.7% (41/535). The median age of females with primary ureteroscopic failure was significantly lower than in females who had successful ureteroscopic access (34 vs 52 years; p = 0.0041). There was no difference in the median age of males with access vs failure (58 vs 57 years; p = 0.3683). Proximal ureteral stones had the highest failure rate for ureteral access at 18.28% (p = 0.006). On multivariable logistic regression, proximal ureteral stone location remained a significant predictor of failure when compared to renal stones (odds ratio [OR] 3.14, p = 0.006). When including only ureteral stones in the multivariable analysis, stone location in the proximal ureter compared to the distal ureter remained the only significant predictor of access failure (OR 0.24, p = 0.015). CONCLUSIONS: A low overall rate of ureteral access failure in unstented patients is shown. Young female patients and proximal ureteral stones were less likely to be accessed primarily. This study provides information that will help urologists counsel their patients preoperatively regarding their likelihood of failing primary URS necessitating a second procedure. This will also help the patient to make an informed decision during the consent process and may guide urologists on selective prestenting in higher risk patients.


Subject(s)
Kidney Calculi/surgery , Ureteral Calculi/surgery , Ureteroscopy/methods , Adult , Age Factors , Aged , Female , Humans , Kidney Calculi/pathology , Male , Middle Aged , Retrospective Studies , Sex Factors , Stents , Treatment Failure , Treatment Outcome , Ureteral Calculi/diagnosis , Ureteral Calculi/pathology , Ureteroscopes
5.
Can J Urol ; 22(2): 7758-62, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25891344

ABSTRACT

Percutaneous nephrolithotomy (PCNL) is the standard treatment for patients with large stone burdens, but can be associated with significant complications. Flexible ureteroscopy is an alternative approach that is less invasive, but often requires multiple procedures. Typically, many factors play a role in the decision to perform PCNL or ureteroscopy. The challenge is that it is difficult to predict which stone burdens will be able to be cleared ureteroscopically. We describe our approach using initial prone ureteroscopy with the transition to standard prone PCNL if required.


Subject(s)
Kidney Calculi/pathology , Kidney Calculi/therapy , Ureteroscopy/methods , Adult , Aged , Female , Humans , Lithotripsy, Laser , Male , Middle Aged , Nephrostomy, Percutaneous , Patient Positioning , Retrospective Studies , Treatment Outcome
6.
Scand J Urol ; 48(5): 426-35, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24611795

ABSTRACT

OBJECTIVE: In countries with widespread prostate cancer screening there has been strong stage migration, but little is known about changes within clinical risk categories. Such data are important for the proper interpretation of studies that recruited cases in an earlier era. The purpose of this study was to examine stage migration between and within clinical risk categories. MATERIAL AND METHODS: Using the population-based National Prostate Cancer Register (NPCR) of Sweden, changes in the distribution of prostate-specific antigen (PSA), Gleason score, tumor stage and volume overall between and within clinical risk categories were examined in 120 228 prostate cancer cases diagnosed from 1998 to 2011. RESULTS: Between 1998 and 2011, there was a two-fold increase in the proportion of low-risk prostate cancer (stage T1/T2, Gleason score 2-6 and PSA <10 ng/ml), from 14% to 28%, and more than a two-fold decrease in the proportion of metastatic disease, from 25% to 11%. The proportion of men in the low-risk category with T1c tumors increased two-fold, from 36% to 71%, and PSA levels between 4 and 6 ng/ml increased from 24% to 38%; T2 tumors decreased from 39% to 20% and PSA between 8 and 10 ng/ml decreased from 24% to 15%. The proportion of men with less than 25% of cores involved with cancer increased from 41% to 52% between 2003-2006 and 2007-2011. CONCLUSIONS: Low-risk cases today have substantially lower tumor volume and PSA levels than low-risk cases diagnosed in 1998, indicating that outcomes in studies that recruited cases in previous decades represent worst case scenarios.


Subject(s)
Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/pathology , Aged , Humans , Male , Middle Aged , Neoplasm Staging , Registries , Risk Assessment , Sweden/epidemiology , Time Factors
7.
Urology ; 81(6): e36-7, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23540862

ABSTRACT

Ectopic ureters are rare congenital mesonephric duct malformations with a higher prevalence in women than men. In women, ectopic ureters are often associated with a duplicated collecting system, whereas in men, ectopic ureters usually drain a single system and are associated with renal dysplasia and obstruction. Presentation and diagnosis generally occurs in the pediatric age group. Herein, we present an unusual case of delayed diagnosis of ectopic insertion of the upper pole ureter in a completely duplicated left kidney causing massive hydroureteronephrosis in an adult man.


Subject(s)
Hydronephrosis/etiology , Ureter/abnormalities , Ureter/diagnostic imaging , Adult , Humans , Magnetic Resonance Imaging , Male , Nephrectomy , Tomography, X-Ray Computed , Ureter/surgery
8.
J Heart Lung Transplant ; 31(9): 1003-8, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22789135

ABSTRACT

BACKGROUND: Common genetic variations influence rejection, infection, drug metabolism, and side effect profiles after pediatric heart transplantation. Reports in adults suggest that genetic background may influence post-transplant renal function. In this multicenter study, we investigated the association of genetic polymorphisms (GPs) in a panel of candidate genes on renal function in 453 pediatric heart transplant recipients. METHODS: We performed genotyping for functional GPs in 19 candidate genes. Renal function was determined annually after transplantation by calculation of the estimated glomerular filtration rate (eGFR). Mixed-effects and Cox proportional hazard models were used to assess recipient characteristics and the effect of GPs on longitudinal eGFR and time to eGFR < 60 mL/min/1.73m(2). RESULTS: Mean age at transplantation was 6.2 ± 6.1 years. Mean follow-up was 5.1 ± 2.5 years. Older age at transplant and black race were independently associated with post-transplant renal dysfunction. Univariate analyses showed FASL (C-843T) T allele (p = 0.014) and HO-1 (A326G) G allele (p = 0.0017) were associated with decreased renal function. After adjusting for age and race, these associations were attenuated (FASL, p = 0.075; HO-1, p = 0.053). We found no associations of other GPs with post-transplant renal function, including GPs in TGFß1, CYP3A5, ABCB1, and ACE. CONCLUSIONS: In this multicenter, large, sample of pediatric heart transplant recipients, we found no strong associations between GPs in 19 candidate genes and post-transplant renal function. Our findings contradict reported associations of CYP3A5 and TGFß1 with renal function and suggest that genotyping for these GPs will not facilitate individualized immunosuppression for the purpose of protecting renal function after pediatric heart transplantation.


Subject(s)
Heart Transplantation , Kidney/physiology , Polymorphism, Genetic , Child , Child, Preschool , Female , Humans , Infant , Male , Prospective Studies
9.
Transplantation ; 91(12): 1326-32, 2011 Jun 27.
Article in English | MEDLINE | ID: mdl-21659963

ABSTRACT

BACKGROUND: Rejection with hemodynamic compromise (RHC) is associated with high mortality in heart recipients. This study investigates the association between genetic polymorphisms and RHC in pediatric heart recipients. METHODS: Data from 532 pediatric heart recipients from six centers in the Pediatric Heart Transplant Study were analyzed for time to RHC by recipient race, age at transplantation, and genotype at 13 genetic polymorphisms (TNF-α A-308G, IL-6 G-174C, INF-γ T+874A, IL-10 G-1082A, C-819T, and C-592A; FAS A-670G, FASL C-843T, and ACE I/D; and VEGF A-2578C, C-1451T, C+405G, and -2549 I/D). RESULTS: RHC occurred in 126 (23.7%) patients during the study period. Adjusting for age and race, IL-10 G-1082A, FAS A-670G, and ACE I/D genotypes were associated with RHC. IL-10 G-1082A GG genotype was associated with decreased risk of RHC with an adjusted hazard ratio (HR) of 0.49 (95% confidence interval [CI], 0.27-0.90; P=0.020). FAS A-670G AA genotype was associated with increased risk of RHC with an adjusted HR of 1.84 (95% CI, 1.25-2.69; P=0.002). ACE II genotype was associated with decreased risk of RHC with an adjusted HR of 0.58 (95% CI, 0.36-0.95; P=0.031). CONCLUSIONS: Recipients with a high anti-inflammatory and immune-regulatory genetic profile (high interleukin-10) were protected from RHC. Conversely, recipients with a pro-apoptotic genetic profile (high Fas) or high angiotensin-1-converting enzyme producing genotype were at increased risk of RHC. This represents progress toward understanding the genetic risk factors of posttransplantation outcomes in pediatric heart recipients.


Subject(s)
Graft Rejection/genetics , Heart Transplantation/adverse effects , Hemodynamics , Polymorphism, Genetic , Adolescent , Angiotensin-Converting Enzyme 2 , Apoptosis , Child , Child, Preschool , Female , Genotype , Heart Transplantation/methods , Humans , Immune System , Infant , Interleukin-10/metabolism , Male , Models, Genetic , Peptidyl-Dipeptidase A/genetics , Risk
10.
Am J Otolaryngol ; 32(1): 82-4, 2011.
Article in English | MEDLINE | ID: mdl-20022667

ABSTRACT

The parapharyngeal space is a complex and well-defined anatomical zone lying lateral to the pharynx and medial to the ramus of the mandible. Although tumors of this space are rare, the parapharyngeal space is difficult to examine clinically; and diagnostic modalities of computerized tomographic scanning and magnetic resonance imaging are primarily used in the evaluation of parapharyngeal space lesions. We present a case report of a second branchial cleft sinus of the parapharyngeal space diagnosed with the assistance of fine needle aspiration (FNA), and we recommend FNA of parapharyngeal masses to provide definitive preoperative diagnoses.


Subject(s)
Branchioma/pathology , Head and Neck Neoplasms/pathology , Nasopharyngeal Neoplasms/pathology , Biopsy, Fine-Needle , Branchioma/diagnostic imaging , Diagnosis, Differential , Head and Neck Neoplasms/diagnostic imaging , Humans , Laryngoscopy , Male , Middle Aged , Nasopharyngeal Neoplasms/diagnostic imaging , Radiography, Interventional , Tomography, X-Ray Computed
11.
J Heart Lung Transplant ; 29(12): 1342-51, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20869265

ABSTRACT

BACKGROUND: Late infections are common causes of morbidity and mortality after pediatric heart transplantation. In this multicenter study from 6 centers, we investigated the association between genetic polymorphisms (GPs) in immune response genes and late post-transplantation infections in 524 patients. METHODS: Late infection was defined as a clinical infectious process occurring >60 days after transplantation and requiring hospitalization, intravenous antimicrobial therapy, or a life-threatening infection requiring oral therapy. All patients provided a blood sample for GP analyses of 18 GPs in cytokine, growth factor, and effector molecule genes by single specific primer-polymerase chain reaction and/or sequencing. Significant associations in univariable analyses were tested in multivariable Cox regression models. RESULTS: Late infection was common, with 48.7% of patients experiencing ≥ 1 late infection, 25.2% had ≥ 1 late bacterial infection, and 30.5% had ≥ 1 late viral infection. Older age at transplantation was a protective factor for late infection, both bacterial and viral (hazard ratio [HR] 0.89-0.92 per 1-year age increase, p < 0.001). Adjusting for age, race, and transplant etiology, late bacterial infection was associated with HMOX1 A+326G AG and GG genotypes (HR, 2.41, 95% confidence interval [CI] 1.35-4.30; p = 0.003) and GZMB A-295G AA genotype (HR, 1.47; 95% CI; 1.03-2.1; p = 0.036). Late viral infection was associated with FAS A-670G GG genotype (HR, 1.42; 95% CI, 1.00-2.00; p = 0.050) in the adjusted model and with CTLA4 A+49G AA and AG genotypes (HR, 1.49; 95% CI, 1.02-2.19; p = 0.041) in univariable analysis. CONCLUSION: We found an association between late bacterial infection and GP of HMOX1, which may control macrophage activation. A weaker association was also found between late viral infection and GP of CTLA4, a regulator of T-cell activation. This represents progress toward understanding the clinical and genetic risk factors of outcomes after transplantation.


Subject(s)
Bacterial Infections/genetics , Genes, MHC Class II/genetics , Genetic Predisposition to Disease , Heart Transplantation/immunology , Polymorphism, Genetic/immunology , Virus Diseases/genetics , Adolescent , Antigens, CD/genetics , CTLA-4 Antigen , Child , Child, Preschool , Cohort Studies , Female , Genotype , Heme Oxygenase-1/genetics , Humans , Infant , Male , Risk Factors
12.
Pediatr Transplant ; 14(7): 891-5, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20649757

ABSTRACT

MMF, the most commonly used adjuvant immunosuppressant in pediatric heart transplantation, has frequent GI adverse events. SNPs in inosine 5'-monophosphate dehydrogenase I (IMPDH1) may contribute to MMF GI intolerance. Phased haplotypes may have more utility than individual SNPs in candidate gene association studies for complex traits. This study defined common IMPDH1 haplotypes and investigated whether these haplotypes influence MMF GI intolerance in 59 pediatric heart recipients. Genotypes were assessed by Taqman analysis of IMPDH1 rs2288553, rs2288549, rs2278293, rs2278294, and rs2228075, and haplotypes were inferred using Arlequin 3.01 software. GI intolerance was defined as diarrhea, vomiting, nausea, or abdominal pain requiring MMF dose holding for > 48 h or MMF discontinuation. GI intolerance occurred in 21 patients (35.6%). Ten IMPDH1 haplotypes were identified in this population. In univariable analyses, one haplotype was strongly associated with MMF GI intolerance with 59.1% of carriers of this haplotype experiencing MMF GI intolerance compared to 21.6% of non-carriers (p = 0.005). In this study, we identify a common IMPDH1 haplotype associated with MMF GI intolerance in a population of pediatric heart transplant patients. This haplotype of interest did not demonstrate stronger association with MMF GI intolerance than an individual IMPDH1 SNP.


Subject(s)
Gastrointestinal Tract/drug effects , Haplotypes , Heart Transplantation/methods , IMP Dehydrogenase/genetics , Mycophenolic Acid/analogs & derivatives , Pediatrics/methods , Adolescent , Child , Child, Preschool , Female , Heterozygote , Humans , Infant , Linkage Disequilibrium , Male , Mycophenolic Acid/adverse effects , Mycophenolic Acid/therapeutic use , Polymorphism, Single Nucleotide , Time Factors
13.
J Heart Lung Transplant ; 29(5): 509-16, 2010 May.
Article in English | MEDLINE | ID: mdl-20061166

ABSTRACT

BACKGROUND: Mycophenolate mofetil (MMF) is an effective and commonly used immunosuppressant but has frequent adverse events. Genetic polymorphisms may contribute to variability in MMF efficacy and related complications. In this study we explore the distribution frequencies of common single nucleotide polymorphisms (SNPs) of IMPDH1, IMPDH2 and ABCC2 and investigate whether these SNPs influence MMF adverse events in 59 pediatric heart recipients. METHODS: Genotypes were assessed by TaqMan analysis of: ABCC2 rs717620; IMPDH2 rs11706052; and IMPDH1 rs2288553, rs2288549, rs2278293, rs2278294 and rs2228075. Gastrointestinal (GI) intolerance was defined as diarrhea, vomiting, nausea or abdominal pain requiring dose-holding for >48 hours or MMF discontinuation. Bone marrow toxicity was evaluated using Common Terminology Criteria for Adverse Events Version 3 (CTCAE). RESULTS: GI intolerance occurred in 21 patients, and 21 had bone marrow toxicity. The ABCC2 rs717620 A variant was significantly associated with GI intolerance leading to drug discontinuation (p < 0.001); the IMPDH1 rs2278294 A variant and rs2228075 A variant were also associated with greater GI intolerance (p = 0.029 and p = 0.002, respectively). The IMPDH2 rs11706052 G variant was associated with more frequent neutropenia requiring dose-holding (p = 0.046). CONCLUSIONS: In this small sample of pediatric heart transplant patients receiving MMF, ABCC2, IMPDH1 and IMPDH2 SNPs were associated with MMF GI intolerance and bone marrow toxicity. Thus, genetic polymorphisms may directly influence MMF adverse events.


Subject(s)
Alleles , Bone Marrow Cells/drug effects , Gastroenteritis/chemically induced , Gastroenteritis/genetics , Heart Transplantation/immunology , IMP Dehydrogenase/genetics , Immunosuppressive Agents/adverse effects , Multidrug Resistance-Associated Proteins/genetics , Mycophenolic Acid/analogs & derivatives , Polymorphism, Single Nucleotide/genetics , Adolescent , Child , Child, Preschool , Cohort Studies , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Female , Genetic Predisposition to Disease/genetics , Genotype , Humans , Immunosuppressive Agents/therapeutic use , Infant , Male , Multidrug Resistance-Associated Protein 2 , Mycophenolic Acid/adverse effects , Mycophenolic Acid/therapeutic use
14.
Am J Med Genet A ; 143A(18): 2098-105, 2007 Sep 15.
Article in English | MEDLINE | ID: mdl-17702011

ABSTRACT

The DYT6 gene for primary torsion dystonia (PTD) was mapped to chromosome 8p21-q22 in two Amish-Mennonite families who shared a haplotype of marker alleles across a 40 cM linked region. The objective of this study was to narrow the DYT6 region, clinically characterize DYT6 dystonia in a larger cohort, and to determine whether DYT6 is associated with dystonia in newly ascertained multiplex families. We systematically examined familial Amish-Mennonite dystonia cases, identifying five additional members from the original families, as well as three other multiplex Amish-Mennonite families, and evaluated the known DYT6 haplotype and recombination events. One of the three new families carried the shared haplotype, whereas the region was excluded in the two other families, suggesting genetic heterogeneity for PTD in the Amish-Mennonites. Clinical features in the five newly identified DYT6 carriers were similar to those initially described. In contrast, affected individuals from the excluded families had a later age of onset (46.9 years vs. 16.1 years in the DYT6), and the dystonia was both more likely to be of focal distribution and begin in the cervical muscles. Typing of additional markers in the DYT6-linked families revealed recombinations that now place the gene in a 23 cM region surrounding the centromere. In summary, the DYT6 gene is in a 23 cM region on chromosome 8q21-22 and does not account for all familial PTD in Amish-Mennonites.


Subject(s)
Christianity , Dystonia/genetics , Genetic Heterogeneity , Chromosomes, Human, Pair 8 , Female , Humans , Male , Pedigree , Phenotype
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