Integration-free induced pluripotent stem cells from three endangered Southeast Asian non-human primate species.

Advanced molecular and cellular technologies provide promising tools for wildlife and biodiversity conservation. Induced pluripotent stem cell (iPSC) technology offers an easily accessible and infinite source of pluripotent stem cells, and have been derived from many threatened wildlife species. This paper describes the first successful integration-free reprogramming of adult somatic cells to iPSCs, and their differentiation, from three endangered Southeast Asian primates: the Celebes Crested Macaque (Macaca nigra), the Lar Gibbon (Hylobates lar), and the Siamang (Symphalangus syndactylus). iPSCs were also generated from the Proboscis Monkey (Nasalis larvatus). Differences in mechanisms could elicit new discoveries regarding primate evolution and development. iPSCs from endangered species provides a safety net in conservation efforts and allows for sustainable sampling for research and conservation, all while providing a platform for the development of further in vitro models of disease.

Differential outcomes in an extended family with constitutional t(11;22)(q23.3;q11.2).

The t(11;22) rearrangement is the most common recurrent familial reciprocal translocation in man. Heterozygote carriers are phenotypically normal but are at risk of subfertility in the male, miscarriages, and producing chromosomally unbalanced offspring. The unbalanced progeny usually results from an extra der(22) chromosome resulting from a 3:1 malsegregation. We present here a family with t(11;22). Of six siblings, three were found to be carriers following prenatal diagnosis of the proband fetus. Neither of the two married carrier siblings have a live born child. In keeping with the prevailing knowledge of the pregnancy outcomes of heterozygote carriers, between the siblings they had recurrent miscarriages, a fetus with a +der(22) chromosome, and other subfertility issues resulting in multiple failed in vitro fertilization cycles with preimplantation genetic diagnosis. However, unlike the siblings, their extended family comprising their heterozygote translocation mother, married aunts and an uncle had normal fertility and a lack of a history of miscarriages or an abnormal child. The differing outcomes may be related to the male partners having additional semen anomalies which may further exacerbate problems associated with the t(11;22). Because the t(11;22) rearrangement tends to run in families, it is recommended that chromosome studies are offered to family members of an affected relative as an option, and provide them with appropriate genetic counseling so that they will have the necessary information with regard to their risk for subfertility, miscarriages, and production of viable unbalanced offspring. Follow-up prenatal diagnosis should also be offered to affected expectant family members, especially after preimplantation genetic diagnosis.

Holoprosencephaly: an antenatally-diagnosed case series and subject review.

INTRODUCTION: Holoprosencephaly (HPE) is an uncommon congenital failure of forebrain development. Although the aetiology is heterogeneous, chromosomal abnormalities or a monogenic defect are the major causes, accounting for about 40% to 50% of HPE cases. At least 7 genes have been positively implicated, including SHH, ZIC2, SIX3, TGIF, PTCH1, GLI2, and TDGF1. CLINICAL PICTURE: Twelve antenatally- and 1 postnatally-diagnosed cases are presented in this study. These comprised 6 amniotic fluid, 3 chorionic villus, 2 fetal blood, 1 peripheral blood, and 1 product of conception. OUTCOME: The total chromosome abnormality rate was 92.3%, comprising predominantly trisomy 13 (66.7%). There was 1 case of trisomy 18, and 3 cases of structural abnormalities, including del13q, del18p, and add4q. CONCLUSION: Despite the poor outcome of an antenatally-diagnosed HPE and the likely decision by parents to opt for a termination of pregnancy, karyotyping and/or genetic studies should be performed to determine if a specific familial genetic or chromosomal abnormality is the cause. At the very least, a detailed chromosome analysis should be carried out on the affected individual. If the result of high resolution karyotyping is normal, Fluorescence in situ hybridisation (FISH) and/or syndrome-specific testing or isolated holoprosencephaly genetic testing may be performed. This information can be useful in making a prognosis and predicting the risk of recurrence.

Trisomy 8 as sole cytogenetic abnormality in a case of chronic lymphocytic leukemia.

A 49-year-old man, who had been diagnosed with chronic lymphocytic leukemia (CLL) in 2002, had a normal karyotype in his bone marrow. Trisomy 8 was demonstrated in his peripheral blood in 2005. Fluorescence in situ hybridization using an LSI CEP 8 probe performed on the archival bone marrow specimen showed three hybridization signals in 40% of 200 interphase cells scored. This confirmed that the trisomy 8 abnormality was present in both the blood and bone marrow samples. Trisomy 8 as the sole chromosomal abnormality in CLL is a very rare finding. The prognostic significance of trisomy 8 in CLL remains to be seen.