Preimplantation genetic diagnosis of chromosome translocations by analysis of polymorphic short tandem repeats

<p><b>INTRODUCTION</b>We aimed to develop and implement a short tandem repeat (STR) polymerase chain reaction alternative to fluorescence in situ hybridisation (FISH) for the preimplantation genetic diagnosis (PGD) of chromosomal translocations.</p><p><b>METHODS</b>Selected informative STRs located on translocated arms of relevant chromosomes were used to discriminate between normal and unbalanced chromosome states in each embryo.</p><p><b>RESULTS</b>PGD cycles were performed on five couples where one spouse carried a balanced translocation. 27 embryos were analysed, of which 12 were normal/balanced, 12 were abnormal/unbalanced and three were indeterminate. Four PGD cycles proceeded to embryo transfer, of which two led to pregnancy. The first pregnancy showed a normal male karyotype, and a healthy baby was delivered at term. A second pregnancy unexpectedly miscarried in the second trimester from unknown causes.</p><p><b>CONCLUSION</b>STR analysis is a simple and suitable alternative to FISH for detecting unbalanced chromosomal states in preimplantation embryos.</p>

ROR2 gene is associated with risk of non-syndromic cleft palate in an Asian population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene has been recently shown to play important roles in palatal development in animal models and resides in the chromosomal region linked to non syndromic cleft lip with or without cleft palate in humans. The aim of this study was to investigate the possible association between ROR2 gene and non-syndromic oral clefts.</p><p><b>METHODS</b>Here we tested 38 eligible single-nucleotide polymorphisms (SNPs) in ROR2 gene in 297 non-syndromic cleft lip with or without cleft palate and in 82 non-syndromic cleft palate case parent trios recruited from Asia and Maryland. Family Based Association Test was used to test for deviation from Mendelian inheritance. Plink software was used to test potential parent of origin effect. Possible maternally mediated in utero effects were assessed using the TRIad Multi-Marker approach under an assumption of mating symmetry in the population.</p><p><b>RESULTS</b>Significant evidence of linkage and association was shown for 3 SNPs (rs7858435, rs10820914 and rs3905385) among 57 Asian non-syndromic cleft palate trios in Family Based Association Tests. P values for these 3 SNPs equaled to 0.000068, 0.000115 and 0.000464 respectively which were all less than the significance level (0.05/38 = 0.0013) adjusted by strict Bonferroni correction. Relevant odds ratios for the risk allele were 3.42 (1.80 - 6.50), 3.45 (1.75 - 6.67) and 2.94 (1.56 - 5.56), respectively. Statistical evidence of linkage and association was not shown for study groups other than non-syndromic cleft palate. Neither evidence for parent-of-origin nor maternal genotypic effect was shown for any of the ROR2 markers in our analysis for all study groups.</p><p><b>CONCLUSION</b>Our results provided evidence of linkage and association between the ROR2 gene and a gene controlling risk to non-syndromic cleft palate.</p>

First successful preimplantation genetic diagnosis in Singapore--avoidance of beta-thalassaemia major

<p><b>INTRODUCTION</b>We report on the first successful preimplantation genetic diagnosis (PGD) in Singapore.</p><p><b>CLINICAL PICTURE</b>A couple who are beta-thalassaemia carriers and have an affected daughter requested for PGD.</p><p><b>TREATMENT</b>Two cycles of PGD were performed on the couple. Beta-thalassaemia mutations were detected using a nested PCR and minisequencing strategy, and unaffected embryos were selected for transfer.</p><p><b>OUTCOME</b>A singleton pregnancy was achieved in the second PGD cycle, resulting in the birth of a healthy baby boy with carrier genotype.</p><p><b>CONCLUSIONS</b>This case report documents the first successful PGD in Singapore, involving a couple at-risk of transmitting beta-thalassaemia major.</p>

Successful preimplantation genetic diagnosis of Hb Bart's hydrops fetalis in Singapore after fresh and frozen embryo replacement cycles

<p><b>INTRODUCTION</b>We report the fi rst successful preimplantation genetic diagnosis (PGD) for Hb Bart's hydrops fetalis in Singapore, involving both fresh and frozen embryo replacement cycles.</p><p><b>CLINICAL PICTURE</b>Two couples who were carriers of the Southeast Asian type double gene deletion (--(SEA) deletion carriers) requested for PGD. Couple A had 2 previous affected pregnancies, while couple B have a child of unknown genotypic status.</p><p><b>TREATMENT</b>One PGD cycle was performed for each couple. The --(SEA) deletion was detected using a gap-PCR strategy. Couple A had 1 fresh-embryo replacement cycle while couple B underwent 2 frozen-embryo replacement cycles.</p><p><b>OUTCOME</b>Couple A achieved a twin pregnancy. Second trimester complications resulted in premature delivery, where 1 baby girl survived. Couple B achieved a singleton pregnancy resulting in delivery of a healthy baby boy. Genotype analysis of all babies confirmed the PGD results consistent with clinically unaffected status.</p><p><b>CONCLUSIONS</b>We have successfully performed PGD to avoid Hb Bart's hydrops fetalis syndrome.</p>

Clinical report: a case of Williams Syndrome and Klinefelter Syndrome

<p><b>INTRODUCTION</b>Williams syndrome (WS) is a rare but well recognised neurodevelopmental disease affecting the connective tissue and the central nervous system. Many patients are identified through the presence of dysmorphic features and associated cardiac abnormalities. Klinefelter syndrome (KS) is associated with gynaecomastia, small testes, azoospermia and elevated gonadotropin levels. They are recognised in the second decade of life by their tall stature and delay in pubertal development. A combination of constitutive WS and KS has yet to be described.</p><p><b>CLINICAL PICTURE</b>We report a child with these genetic aberrations, highlighting the clinical characteristics of such an individual.</p><p><b>CONCLUSION</b>The manifestations and interactions of both conditions are also discussed.</p>