TITLE:
Atelosteogenesis Type 2/Diastrophic Dysplasia Phenotypic Spectrum: From Prenatal to Preimplantation Genetic Diagnosis
AUTHORS:
Eduardo P. Mattos, Jose Antonio A. Magalhaes, Laureane Mittaz-Crettol, Ricardo Azambuja, Lilian Okada, Denise P. Cavalcanti, Juliana Cuzzi, Mariangela Badalotti, Rafaella Petracco, Alvaro Petracco, Lavinia Schuler-Faccini, Maria Teresa V. Sanseverino
KEYWORDS:
Atelosteogenesis Type 2, Diastrophic Dysplasia, Preimplantation Genetic Diagnosis, Prenatal Diagnosis, Skeletal Dysplasia
JOURNAL NAME:
Open Journal of Obstetrics and Gynecology,
Vol.4 No.7,
May
30,
2014
ABSTRACT: Atelosteogenesis type II (AO2)
and diastrophic dysplasia (DTD) are two recessively inherited, severe skeletal
dysplasias caused by mutations in the SLC26A2 gene. AO2 is an invariably lethal
condition, while DTD patients may reach adult life, although both diseases have
overlapping diagnostic features. Here we report a patient with an intermediate
phenotype between AO2 and DTD and present the successful application of
preimplantation genetic diagnosis (PGD) in this situation. Sequencing of SLC26A2 alleles in the infant identified two
compound heterozygous mutations, p.Arg178Ter and p.Arg279Trp, of paternal and
maternal origin, respectively. At request from the parents, PGD was developed
by haplotype mapping of parental SLC26A2 alleles in eleven five-day embryos. Transference to the mother was
attempted twice, finally resulting in pregnancy and delivery of a healthy baby.
This exemplifies the utility of PGD for inherited lethal conditions with a significant
risk of recurrence, and highlights the importance of accurate diagnosis of
skeletal dysplasias with prenatal manifestation.