title: Nine-year experience in Gaucher disease diagnosis at the Spanish reference center Fundación Jiménez Díaz.
abstract: BACKGROUND
  Fundación Jiménez Díaz (FJD) is a reference center for genetic diagnosis of Gaucher disease (GD) in Spain. Genetic analyses of acid β-glucosidase (GBA) gene using different techniques were performed to search for new mutations, in addition to those previously and most frequently found in the Spanish population. Additionally, the study of the chitotriosidase (CHIT1)gene was used to assess the inflammatory status of patients in the follow-up of enzyme replacement therapy (ERT). We present the genetic data gathered during the last nine years at FJD.
  
  
  METHODS
  Blood samples from patients with suspected GD were collected for enzymatic and genetic analyses. The genetic analysis was performed on DNA from 124 unrelated suspected cases and 57 relatives from 2007 to 2015, starting with a mutational screening kit, followed by Sanger sequencing of the entire gene and other techniques to look for deletions.CHIT1was also studied to assess the reliability of this biomarker.
  
  
  RESULTS
  In 46 out of 93 GD patients (49.5%) the two mutant alleles were found. We detected 21 different mutations. The most common mutation was N370S (c.126A > G; p.Asp409Ser current nomenclature) (in 50.5% of patients), followed by L444P (c.1448T > C; p.Leu483Pro current nomenclature) (in 24.7%). The most common heterozygous compound genotype observed (18.3%) was c.1226A > G/c.1448T > C (N370S/L444P). Two novel mutations were found (del. Ex.4-11 and c.1296G > T; pW432C), as well as p.S146L, only once previously reported. Two patients showed the homozygous state for the duplication ofCHIT1.
  
  
  CONCLUSIONS
  N370S and L444P are the most common mutations and other mutations associated to Parkinson's disease have been observed. This should be taken into account in the genetic counseling of GD patients.
authors.affiliation: Department of Genetics, Health Research Institute-Jimenez Diaz Foundation University Hospital (IIS-FJD), Universidad Autónoma de Madrid, Spain; Department of Clinical Analysis, Hospital Universitario Clínico San Carlos, Madrid, Spain.
authors.forename: N V
authors.initials: NV
authors.lastname: Ortiz-Cabrera
authors.affiliation: Department of Genetics, Health Research Institute-Jimenez Diaz Foundation University Hospital (IIS-FJD), Universidad Autónoma de Madrid, Spain; CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Gallego-Merlo
authors.affiliation: Department of Genetics, Health Research Institute-Jimenez Diaz Foundation University Hospital (IIS-FJD), Universidad Autónoma de Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Vélez-Monsalve
authors.affiliation: Diabetes, Nephrology and Vascular Pathology Research Laboratory, Health Research Institute-Jimenez Diaz Foundation University Hospital (IIS-FJD), Universidad Autónoma de Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: de Nicolas
authors.affiliation: Diabetes, Nephrology and Vascular Pathology Research Laboratory, Health Research Institute-Jimenez Diaz Foundation University Hospital (IIS-FJD), Universidad Autónoma de Madrid, Spain.
authors.forename: S Fontao
authors.initials: SF
authors.lastname: Mas
authors.affiliation: Department of Genetics, Health Research Institute-Jimenez Diaz Foundation University Hospital (IIS-FJD), Universidad Autónoma de Madrid, Spain; CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Ayuso
authors.affiliation: Department of Genetics, Health Research Institute-Jimenez Diaz Foundation University Hospital (IIS-FJD), Universidad Autónoma de Madrid, Spain; CIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Trujillo-Tiebas
keywords: Chitotriosidase; ERT, enzyme replacement therapy; FJD, Fundación Jiménez Díaz; GBA gene; GBA, acid β-glucosidase; GD, Gaucher disease; Gaucher disease; Spanish Gaucher disease