title: Two Patients with Severe Short Stature due to a FBN1 Mutation (p.Ala1728Val) with a Mild Form of Acromicric Dysplasia.
abstract: BACKGROUND
  Acromicric dysplasia (AD) and geleophysic dysplasia 2 (GD2) belong to the category of acromelic dysplasia syndromes, consisting of severe short stature, short hands and feet and skin thickening. Both can result from missense mutations in the transforming growth factor beta 5 domain of the fibrillin-1 gene (FBN1).
  
  
  METHODS
  Two patients (P1 age 10, and P2 age 7) from unrelated families presented to their endocrinologist with severe short stature (approx. -4 SDS). They were otherwise asymptomatic and only had mild facial dysmorphisms. Extensive endocrine work-up did not reveal an underlying etiology. Exome sequencing was performed in each family.
  
  
  RESULTS
  Exome sequencing identified the presence of the same heterozygous missense variant c.C5183T (p.Ala1728Val) in the FBN1 gene in both P1 and P2. This variant was previously reported in a patient with GD2 and associated cardiac valvulopathy and hepatomegaly. Detailed clinical re-examination, cardiac and skeletal imaging did not reveal any abnormalities in P1 or P2 other than mild hip dysplasia.
  
  
  CONCLUSIONS
  This report broadens the phenotypic spectrum of growth disorders associated with FBN1 mutations. Identical mutations give rise to a wide phenotypic spectrum, ranging from isolated short stature to a more classic picture of GD2 with cardiac involvement, distinct facial dysmorphisms and various skeletal anomalies.
authors.affiliation: Division of Endocrinology, Cincinnati Center for Growth Disorders, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Christiaan
authors.initials: C
authors.lastname: de Bruin
authors.forename: Courtney
authors.initials: C
authors.lastname: Finlayson
authors.forename: Mariana F A
authors.initials: MF
authors.lastname: Funari
authors.forename: Gabriela A
authors.initials: GA
authors.lastname: Vasques
authors.forename: Bruna
authors.initials: B
authors.lastname: Lucheze Freire
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Lerario
authors.forename: Melissa
authors.initials: M
authors.lastname: Andrew
authors.forename: Vivian
authors.initials: V
authors.lastname: Hwa
authors.forename: Andrew
authors.initials: A
authors.lastname: Dauber
authors.forename: Alexander A L
authors.initials: AA
authors.lastname: Jorge
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001848:Bone Diseases, Developmental / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D059472:Exome; D005260:Female; D000071838:Fibrillin-1 / Q000235:genetics*; D006130:Growth Disorders / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D017880:Limb Deformities, Congenital / Q000235:genetics* / Q000473:pathology; D008297:Male; D020125:Mutation, Missense; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; C000605722:FBN1 protein, human; D054392:Adipokines