The National Institute on Disability and Rehabilitation Research burn model system database: a tool for the multicenter study of the outcome of burn injury.

Advances in critical care and surgical management have significantly improved survival after burn injury over the past several decades. However, today, survival alone is an insufficient outcome. In 1994, the National Institute on Disability and Rehabilitation Research (NIDRR) created a burn model system program to evaluate the long-term sequelae of burn injuries. As part of this multicenter program, a comprehensive demographic and outcome database was developed to facilitate the study of a number of functional and psychosocial outcomes after burns. The purpose of this study is to review the database design and structure as well as the data obtained during the last 10 years. This is a descriptive study of the NIDRR database structure as well as the patient data obtained from the four participating burn centers from 1994 to 2004. Data obtained during hospitalization and at 6, 12, and 24 months after discharge were reviewed and descriptive statistics were calculated for select database fields. The database is divided into several subsections, including demographics, injury complications, patient disposition, and functional and psychological surveys. A total of 4600 patients have been entered into the NIDRR database. To date, 3449 (75%) patients were alive at discharged and consented to follow-up data collection. The NIDRR database provides an expansive repository of patient, injury, and outcome data that can be used to analyze the impact of burn injury on physical and psychosocial function and for the design of interventions to enhance the quality of life of burn survivors.

Mutations in the Wolfram syndrome type 1 gene (WFS1) define a clinical entity of dominant low-frequency sensorineural hearing loss.

OBJECTIVE: To describe low-frequency sensorineural hearing loss (LFSNHL) inherited as a dominant trait in 3 families and in 1 sporadic case. DESIGN: Longitudinal clinical study from 1968 to 2001. SETTING: Tertiary care hospital; field studies conducted by molecular genetic research laboratory. PARTICIPANTS: Dominant LFSNHL families. INTERVENTIONS: Questionnaires, serial audiograms, and interviews, correlated with molecular genetic data. OUTCOME MEASURES: Symptoms, age of onset, serial audiometric data, and hearing aid use. RESULTS: Low-frequency sensorineural hearing loss is typically diagnosed in the first decade and slowly progresses over decades; LFSNHL is often asymptomatic in young patients, few of whom use hearing aids. Speech perception becomes affected in later decades when patients develop high-frequency loss. Even children with a strong family history of dominant LFSNHL were not monitored routinely. Penetrance appears complete in that all individuals with a genetic mutation developed hearing loss. CONCLUSIONS: Dominant LFSNHL is most commonly caused by mutations in the Wolfram syndrome type 1 gene (WFS1). Mutations in WFS1 also cause a rare recessive syndromic form of hearing loss known as Wolfram syndrome or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Routine newborn hearing screening methods will not typically identify hearing loss affecting frequencies below 2000 Hz; thus, children at risk must be specifically monitored. Genetic counseling and genetic testing may be useful in the management of patients with this type of hearing loss.

Mutation of a transcription factor, TFCP2L3, causes progressive autosomal dominant hearing loss, DFNA28.

We ascertained a large American family with an autosomal dominant form of progressive non-syndromic sensorineural hearing loss. After excluding linkage to known deafness loci, we performed a genome-wide scan and found linkage to marker GAAT1A4 on chromosome 8q22 (LOD=5.12 at theta=0), and this locus was designated DFNA28. Sequencing of six candidate genes in the 1.4 cM linked region identified a frameshift mutation (1609-1610insC) resulting in a premature translation stop codon in exon 14 of the gene TFCP2L3 (transcription factor cellular promoter 2-like 3). TFCP2L3 is a member of a family of transcription factor genes whose archetype is TFCP2, a mammalian homolog of the Drosophila gene grainyhead. Northern blot analyses and in situ hybridization studies show that mouse Tfcp2l3 is expressed in many epithelial tissues, including cells lining the cochlear duct, at embryonic day 18.5 and postnatal day 5.