ß 2008 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 146A:514–516 (2008) Research Letter Placental Hypoplasia in Maternal Uniparental Disomy for Chromosome 7 Kazuki Yamazawa, 1 Masayo Kagami, 1 Masamichi Ogawa, 2 Reiko Horikawa, 3 and Tsutomu Ogata 1 * 1 Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, Tokyo, Japan 2 Ogawa Clinic Pediatrics and Endocrinology, Nagoya, Japan 3 Division of Endocrinology and Metabolism, National Center for Child Health and Development, Tokyo, Japan Received 29 May 2007; Accepted 16 September 2007 How to cite this article: Yamazawa K, Kagami M, Ogawa M, Horikawa R, Ogata T. 2008. Placental hypoplasia in maternal uniparental disomy for chromosome 7. Am J Med Genet Part A 146A:514 – 516. To the Editor: Maternal uniparental disomy for chromosome 7 (mat upd(7)) refers to a condition in which both of the two chromosome 7 homologues are inherited from the mother [Kotzot et al., 2000]. This condition accounts for 7–10% of patients with Silver–Russell syndrome (SRS) characterized by pre- and postnatal growth failure, relative macrocephaly, triangular face, and body asymmetry [Kotzot et al., 2000]. Since maternal heterodisomy as well as isodisomy has been found for all the regions of chromosome 7, and the phenotype is constant in affected individuals, it seems likely that an imprinted gene(s), rather than the unmasking of a recessive allele by iso- disomy, is the cause of the SRS phenotype [Preece et al., 1999]. Furthermore, molecular studies in key patients have suggested two separate critical regions for SRS (7p11.2 – p13 and 7q31 – qter), and candidate imprinted genes such as GRB10 at 7p12 and PEG1/ MEST at 7q32.2 have been identified, together with PEG10 at 7q21 [reviewed in Hitchins et al., 2001]. In addition, loss of the paternal allele of FOXP2 at 7q31 could be relevant to language deficits in mat upd(7) patients [Feuk et al., 2006]. However, the gene(s) responsible for the SRS features has not been identified to date. Imprinted genes are known to play a critical role in placental development [Fowden et al., 2006]. Nevertheless, placental phenotype has been poorly documented in mat upd(7), in contrast to the well described clinical features. Thus, we examined placental weight in three Japanese patients with mat upd(7) (cases 1 – 3), as well as that of a child born to case 3. This study was approved by the Insti- tutional Review Board Committee at National Center for Child Health and Development, and written informed consent was obtained from each patient or the parent(s). Cases 1–3 were found to have mat upd(7), following molecular studies in 61 Japanese SRS patients. The methods were as described previously [Kosaki et al., 2000; Kagami et al., 2007]. Leukocyte genomic DNA was treated with bisulphite using an EZ DNA methylation kit (Zymo Research, Orange, CA) that converts cytosine except when it is methylat- ed into uracil. Methylation analysis was performed for the differentially methylated region of PEG1/ MEST using methylated and unmethylated allele- specific PCR primers. Results indicated the presence of only methylated allele of maternal origin in cases 1–3 (Fig. 1A). Subsequently, microsatellite analysis was carried out for nine loci widely dispersed on chromosome 7, showing full maternal isodisomy in cases 1 and 2 and heterodisomy in case 3 (Fig. 1B,C). Microsatellite genotyping was also performed for additional five autosomal loci, confirming the pater- nity in cases 1 – 3. Clinical phenotypes including placental size of cases 1 – 3 are shown in Table I. Cases 1 – 3 were born at term, and had pre- and postnatal growth failure and several SRS-compatible features. The placenta was recorded to be small in cases 1 – 3 with no gross macroscopic abnormalities, although histological findings had not been examined, and there were no preserved placental samples. Oligohydramnios was also noticed during the pregnancy of case 1. Chorionic villus sampling was not performed in cases 1–3. Case 3 gave birth to a male infant with a birth weight of 2.94 kg (0.1 SD) by a caesarean section at *Correspondence to: Tsutomu Ogata, M.D., Department of Endocri- nology and Metabolism, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan. E-mail: tomogata@nch.go.jp DOI 10.1002/ajmg.a.32125