The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2

Next-generation mate-pair sequencing (MPS) has revealed that many constitutional complex chromosomal rearrangements (CCRs) are associated with local shattering of chromosomal regions (chromothripsis). Although MPS promises to identify the molecular basis of the abnormal phenotypes associated with many CCRs, none of the reported mate-pair sequenced complex rearrangements have been simultaneously studied with state-of-the art molecular cytogenetic techniques. Here, we studied chromothripsis-associated CCR involving chromosomes 2, 5 and 7, associated with global developmental and psychomotor delay and severe speech disorder. We identified three truncated genes: CDH12, DGKB and FOXP2, confirming the role of FOXP2 in severe speech disorder, and suggestive roles of CDH12 and/or DGKB for the global developmental and psychomotor delay. Our study confirmes the power of MPS for detecting breakpoints and truncated genes at near nucleotide resolution in chromothripsis. However, only by combining MPS data with conventional G-banding and extensive fluorescence in situ hybridizations could we delineate the precise structure of the derivative chromosomes.     

One-Month Serotonin Infusion Results in a Prolonged Fall in Blood Pressure in the Deoxycorticosterone Acetate (DOCA) Salt Hypertensive Rat

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Psychosocial impact of obstetric fistula in women presenting for surgical care in Tanzania

Introduction and hypothesis

World Health Organisation data suggest that two million women live with the physical and psychosocial effects of obstetric fistula. As part of an expanded fistula programme in Tanzania, Comprehensive Community Based Rehabilitation in Tanzania (CCBRT) introduced an evaluation strategy to include impact of surgery on psychosocial aspects of obstetric fistula. This is an initial report documenting morbidity on admission.

Methods

A questionnaire assessing the impact of obstetric fistula was developed taking into account literature in the field including sections on: patient contact information, transport costs and a set of statements regarding the effects of fistula. The effects were spread across five domains: the physical consequences of obstetric fistula, the effects of a difficult delivery and possible stillbirth, the experience of isolation, the inability to undertake daily living activities and feelings of depression. The questionnaire was administered in Kiswahili by Tanzanian counsellors shortly after admission of patients onto the fistula ward.

Results

A total of 100 fistula patients reported high rates of physical and psychosocial morbidity. Over half of the patients said they would not have been able to access treatment without the transport costs being covered.

Conclusions

Fistula patients are affected by extremely high rates of physical and psychosocial morbidity. Further work is required to confirm these findings, validate assessment tools and assess contributing factors in greater detail over time, such as the effect of stillbirth, as well as the impact of surgery.