title: Novel mutations in geleophysic dysplasia type 1.
abstract: Geleophysic dysplasia (GD) is a rare genetic disorder characterized by acromelic dysplasia. Geleophysic dysplasia type 1 (MIM 231050) is autosomal recessive and is caused by homozygous or compound heterozygous mutation in the ADAMTSL2 (a disintegrin and metalloproteinase with thrombosponding repeats-like 2) gene. Geleophysic dysplasia type 2 (MIM 614185) is autosomal dominant and is caused by heterozygous mutation in the fibrillin 1 (FBN1) gene. Here, we present the clinical and histopathologic findings in a child with GD with newly identified ADAMTSL2 mutations. The 1st mutation was probably a pathogenic one, c.[1934G>A] p.[Arg645His], located in exon 13; the 2nd, in intron 8, was probably changing a splice site. While the light and electron microscopic findings were similar to those previously described, hydrocephalus due to aqueductal stenosis might be a new associated finding in these patients. This child with these 2 novel mutations also had an aggressive clinical course with early-onset progressive cardiac valvular disease.
authors.affiliation: 1  Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Prashob
authors.initials: P
authors.lastname: Porayette
authors.forename: Deborah
authors.initials: D
authors.lastname: Fruitman
authors.forename: Julie L
authors.initials: JL
authors.lastname: Lauzon
authors.forename: Carine
authors.initials: C
authors.lastname: Le Goff
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Sanders
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pinto-Rojas
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Perez-Atayde
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000071096:ADAMTS Proteins; D000015:Abnormalities, Multiple / Q000235:genetics; D001848:Bone Diseases, Developmental / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007223:Infant; D017880:Limb Deformities, Congenital / Q000235:genetics* / Q000473:pathology*; D008297:Male; D009154:Mutation
chemical_list: D051722:ADAM Proteins; D000071096:ADAMTS Proteins; C000590227:ADAMTSL2 protein, human
keywords: ADAMTSL2; congenital heart disease; geleophysic dysplasia