title: Recurrence of achondrogenesis type II within the same family: evidence for germline mosaicism.
abstract: Achondrogenesis type II is a lethal skeletal dysplasia caused by new dominant mutations within the type II collagen gene (COL2A1). Here we report on two pregnancies of a healthy, nonconsanguineous young couple. In the first pregnancy, severe micromelia and generalized edema were noted on ultrasound at 21 weeks' gestation. Clinical, radiological, and histological evaluation of the fetus after termination of the pregnancy showed typical findings of achondrogenesis type II. In the second pregnancy, fetal hygroma was noted at 11 weeks' gestation. Similar clinical, radiographic, and histologic findings were observed in the second fetus, suggesting the recurrence of achondrogenesis II within this family. Molecular analysis of genomic DNA extracted from amniotic cells of the second fetus revealed heterozygosity for a 1340G > A missense mutation (G316D) in the COL2A1 gene. This mutation was not found in the parents. Although, we could not evaluate the presence of this mutation in the first fetus, we strongly believe that our data are in favor of germline mosaicism as the most likely explanation for the recurrence of type II achondrogenesis in both sibs.
authors.affiliation: Centre de Génétique, Hôpital d'Enfants, Dijon, France. laurence.faivre@chu-dijon.fr
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Martine
authors.initials: M
authors.lastname: Le Merrer
authors.forename: Serges
authors.initials: S
authors.lastname: Douvier
authors.forename: Nicole
authors.initials: N
authors.lastname: Laurent
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.forename: Thierry
authors.initials: T
authors.lastname: Rousseau
authors.forename: Inge
authors.initials: I
authors.lastname: Vereecke
authors.forename: Paul
authors.initials: P
authors.lastname: Sagot
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Delezoide
authors.forename: Paul
authors.initials: P
authors.lastname: Coucke
authors.forename: Geert
authors.initials: G
authors.lastname: Mortier
mesh_terms: D000130:Achondroplasia / Q000000981:diagnostic imaging / Q000235:genetics*; D000328:Adult; D024043:Collagen Type II / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005315:Fetal Diseases / Q000000981:diagnostic imaging / Q000473:pathology*; D005854:Germ Cells; D006801:Humans; D008297:Male; D009030:Mosaicism; D009154:Mutation / Q000235:genetics*; D011859:Radiography
chemical_list: D024043:Collagen Type II