title: Successful PGD for late infantile neuronal ceroid lipofuscinosis achieved by combined chromosome and TPP1 gene analysis.
abstract: Late infantile neuronal ceroid lipofuscinosis (NCL-2) is a severe debilitating autosomal recessive disease caused by mutations in TPP1. There are no effective treatments, resulting in early childhood death. A couple with two affected children presented for reproductive genetic counselling and chose to undertake IVF and preimplantation genetic diagnosis (PGD) to avoid the possibility of another affected child. However, DNA testing revealed only one mutation in the proband inherited from mother. Linkage analysis identified five informative linked short tandem repeat markers to aid the genetic diagnosis. Following IVF, five cleavage-stage embryos were biopsied and blastomeres were first subjected to whole-genome amplification, then a series of down-stream molecular genetic analyses to diagnose TPP1 genotype and finally array comparative genomic hybridization (CGH) to assess the chromosomal ploidy of each embryo. Two unaffected euploid embryos were identified for transfer. One was transferred on day 5 resulting in an ongoing pregnancy. Confirmatory prenatal diagnosis by amniocentesis showed concordance of the embryo and fetal diagnosis. As far as is known, this is the first successful report of PGD for NCL-2 using double-factor PGD with simultaneous single-gene testing and array CGH to identify an unaffected and chromosomally normal embryo for transfer.
authors.affiliation: The State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, PR China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Shen
authors.forename: David Stephen
authors.initials: DS
authors.lastname: Cram
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Lingbo
authors.initials: L
authors.lastname: Cai
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Yang
authors.forename: Xueping
authors.initials: X
authors.lastname: Sun
authors.forename: Yugui
authors.initials: Y
authors.lastname: Cui
authors.forename: Jiayin
authors.initials: J
authors.lastname: Liu
mesh_terms: D000328:Adult; D000626:Aminopeptidases / Q000235:genetics* / Q000378:metabolism; D002869:Chromosome Aberrations / Q000196:embryology*; D002970:Cleavage Stage, Ovum / Q000378:metabolism*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics* / Q000378:metabolism; D005191:Family Characteristics; D005192:Family Health; D005260:Female; D005307:Fertilization in Vitro; D005817:Genetic Counseling; D006801:Humans; D008297:Male; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000175:diagnosis* / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D019836:Preimplantation Diagnosis; D057057:Serine Proteases / Q000235:genetics* / Q000378:metabolism; D056826:Single Embryo Transfer; D000091346:Tripeptidyl-Peptidase 1
chemical_list: D000091346:Tripeptidyl-Peptidase 1; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C000717267:TPP1 protein, human
keywords: aneuploid screening; array comparative genomic hybridization; fluorescent PCR; late infantile neuronal ceroid lipofuscinosis; preimplantation genetic diagnosis; whole-genome amplification