Preventing mucopolysaccharidosis type II (Hunter syndrome): PGD and establishing a Hunter (46, XX) stem cell line

• Published in: Prenatal diagnosis Vol. 31; no. 9; pp. 853 - 860
• Main Authors: Altarescu, Gheona, Renbaum, Paul, Eldar-Geva, Talia, Brooks, Baruch, Varshaver, Irit, Avitzour, Mical, Margalioth, Ehud J., Levy-Lahad, Ephrat, Elstein, Deborah, Epsztejn-Litman, Silvina, Eiges, Rachel
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.09.2011; Wiley
• Subjects: Adult; Biological and medical sciences; Blastomeres; Cell Line; Delivery. Postpartum. Lactation; DNA - analysis; Embryo Culture Techniques; Embryo Transfer; Female; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Gynecology. Andrology. Obstetrics; Humans; Hunter syndrome; Iduronate Sulfatase - genetics; Male; Medical sciences; Microsatellite Repeats; Molecular and cellular biology; Mucopolysaccharidosis II - prevention & control; mucopolysaccharidosis type II; multiplex PCR; Mutation; Polar Bodies; polar body; Polymerase Chain Reaction - methods; Polymorphism, Genetic - genetics; Pregnancy; Pregnancy Outcome; Preimplantation Diagnosis - methods; preimplantation genetic diagnosis; single cell; Sperm Injections, Intracytoplasmic; stem cell; Stem Cells; Treatment Outcome; Twins; Multiplex polymerase chain reaction; Stem cell; Gynecology; Diseases of the osteoarticular system; Neonatology; Metabolic diseases; Hunter's syndrome; Enzymopathy; Obstetrics; mucopolysaccharidosis type II; Genetic disease; Polar body; Prevention; multiplex PCR; Preimplantation diagnosis; Hunter syndrome; single cell; Cell line; Genetics; Carbohydrate; preimplantation genetic diagnosis; Molecular biology
• ISSN: 0197-3851; 1097-0223
• DOI: 10.1002/pd.2786

Objectives Preimplantation genetic diagnosis (PGD) enables the identification of affected embryos prior to implantation. We present for the first time three families in which either the oocytes or embryos obtained from female carriers of mutations in the iduronate‐2‐sulfatase (IDS) gene underwent PGD for mucopolysaccharidosis type II (Hunter syndrome). Furthermore, we report the first ever derivation of a Hunter's syndrome (46, XX) human stem cell line from embryos (HESC) carrying the IDS and oculocutaneus albinism type 2 mutations. Methods Combined polar body (PB) 1 and 2 or a single cell of a six‐ to eight‐cell embryo (blastomere) was used for genetic analysis by multiplex polymerase chain reaction assay using six microsatellite polymorphic markers flanking the gene and mutation. Results One couple underwent four PB‐PGD cycles, with birth of a healthy girl; the second couple with one PB‐PGD cycle had healthy twins; the third couple underwent seven cycles of double PGD for Hunter and Albinism syndrome with birth of healthy twins. One novel Hunter 46, XX HESC line was established displaying typical characteristics of HESC cells. Conclusions PGD is a reliable method to prevent pregnancy of children affected with Hunter syndrome. In addition, derived HESC can be further utilized for drug testing and better understanding of the pathogenesis of this syndrome. Copyright © 2011 John Wiley & Sons, Ltd.