TY - JOUR
T1 - Atelosteogenesis Type 2/Diastrophic Dysplasia Phenotypic Spectrum
T2 - From Prenatal to Preimplantation Genetic Diagnosis
AU - Preusser Mattos, Eduardo
AU - A. Magalhães, José Antônio
AU - Mittaz-Crettol, Laureane
AU - Azambuja, Ricardo
AU - Azambuja, Ricardo
AU - Okada, Lilian
AU - P. Cavalcanti, Denise
AU - Cuzzi, Juliana
AU - Badalotti, Mariangela
AU - Petracco, Rafaella
AU - Petracco, Alvaro
AU - Schuler-Faccini, Lavinia
AU - Vieira Sanseverino, Maria Teresa
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
U2 - 10.4236/ojog.2014.47060
DO - 10.4236/ojog.2014.47060
M3 - Article
SN - 2160-8806
SP - 399
EP - 404
JO - Open Journal of Obstetrics and Gynecology
JF - Open Journal of Obstetrics and Gynecology
ER -