Trophoblast CD200 expression in successful human pregancies and missed abortions.

Presence of the CD200 immune check-point inhibitor at the feto-maternal interface is linked to prevention of spontaneous abortion in mice and humans. In human missed abortions (MA), absence of Th17-driven inflammation has been attributed to expression of villus trophoblast CD200 quantified using immunohistochemistry. While rapid aneuploidy (QF-PCR) testing linked low CD200 to pregnancy failure, data showing normal VT CD200 in first trimester normal pregnancy and in abortion of chromosomally abnormal embryos has not been demonstrated. The present report shows normal CD200 in a 7 week gestation termination with normal male QF-PCR and in a 10 week male trisomy 18 MA.

Apparent transmission distortion of a pericentric chromosome one inversion in a large multi-generation pedigree.

Pericentric chromosome inversions are often associated with infertility, recurrent pregnancy loss, and an increased risk for offspring with congenital anomalies. We report on a chromosome 1 inversion between 1p36.21 and 1q42.13, one of the largest described familial pericentric inversions of chromosome 1. The inversion was ascertained following the birth of a female with multiple congenital anomalies due to a recombinant chromosome 1. The inversion was subsequently detected or inferred in 16 healthy individuals over five generations. Interestingly, with a ratio of 16 carriers to 6 noncarriers, there appears to be transmission distortion of the inverted chromosome 1 within the family. Although there is no reported difficulty conceiving in the family, the risk of miscarriage is higher than predicted at 34% (13/38). The recurrence risk of a recombinant chromosome also appears to be lower than expected based on the mode of ascertainment. This case contributes to the spectrum of clinical features of chromosome 1 recombinants and raises the question of whether or not there is a selective advantage of the inverted chromosome at meiosis, conception, or post-zygotically that has contributed to transmission distortion of the inverted chromosome.

A novel mutation in the IHH gene causes brachydactyly type A1: a 95-year-old mystery resolved.

Brachydactyly type A1 (BDA1) was the first disorder described in terms of autosomal dominant Mendelian inheritance. Early in the 1900s Farabee and Drinkwater described a number of families with BDA1. Examination of two of Drinkwater's families has revealed that, although they are not known to be related, both share a common mutation within the Indian hedgehog gene ( IHH). This novel mutation is a guanine to adenine transition at nucleotide 298, resulting in an Asn100Asp amino acid substitution. Both families demonstrate significant intrafamilial phenotypic heterogeneity among the affected individuals. Examination of single nucleotide polymorphisms (SNP) has shown that the affected individuals in both families share SNPs within IHH consistent with that of a common founder. The identification of the same mutation in these families has answered a question that is nearly a century old about the genetic cause of their disease and supports the hypothesis that IHH plays a pivotal role in normal human skeletogenesis.