title: Detection of epidermal thickening in GJB2 carriers with epidermal US.
abstract: OBJECTIVE
  To measure epidermal thickness by using skin ultrasonography (US) in a series of healthy control subjects and obligate carriers for the worldwide most frequent form of congenital hearing loss owing to the mutated alleles of the connexin 26 gene (GJB2).
  
  
  METHODS
  The patent for the protocol, coupled with a new sonographic probe specifically designed to analyze epidermal thickness and a dedicated algorithm to classify individuals in groups, is pending. Institutional ethics committee approval and patient consent were obtained. After a preliminary study in 23 subjects aimed to define the best body site and instrument and protocol for US, a total of 303 individuals (237 healthy subjects, 51 carriers, and 15 homozygotes) were tested at midline forehead by using a linear large-band probe with a frequency ranging from 6 to 15 MHz to determine epidermal thickness. Variance and linear regression analyses were performed. Regression coefficients were then used to obtain measurements of thickness corrected for age and sex.
  
  
  RESULTS
  GJB2 obligate carriers had a significant increase in epidermal thickness compared with control subjects. GJB2 status explains about 50.0% of this variability, whereas an additional 25.0% is explained by sex and age. Results led to the development of a possible screening protocol with a 98.0% sensitivity and 92.8% specificity in subjects aged 2080 years, with a likelihood ratio of a positive test of 14:1. Even better results (100% sensitivity and 98.9% specificity) were obtained in an analysis of people of only reproductive age.
  
  
  CONCLUSIONS
  Epidermal thickening in the white population owing to GJB2 carrier status can be detected by using US. This measurement could provide a simple, noninvasive, rapid, and sensitive test for carrier screening.
authors.affiliation: Radiology Unit, Institute of Child Health, Istituto di Ricovero e Cura a Carattere Scientifico, Burlo Garofolo Hospital, Trieste, Italy.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Guastalla
authors.forename: Veronica Ileana
authors.initials: VI
authors.lastname: Guerci
authors.forename: Antonella
authors.initials: A
authors.lastname: Fabretto
authors.forename: Flavio
authors.initials: F
authors.lastname: Faletra
authors.forename: Domenico Leonardo
authors.initials: DL
authors.lastname: Grasso
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Zocconi
authors.forename: Despina
authors.initials: D
authors.lastname: Stefanidou
authors.forename: Pio
authors.initials: P
authors.lastname: D'Adamo
authors.forename: Luca
authors.initials: L
authors.lastname: Ronfani
authors.forename: Marcella
authors.initials: M
authors.lastname: Montico
authors.forename: Marcello
authors.initials: M
authors.lastname: Morgutti
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004817:Epidermis / Q000000981:diagnostic imaging*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D034381:Hearing Loss / Q000453:epidemiology* / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014463:Ultrasonography / Q000706:statistics & numerical data*; D055815:Young Adult
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26