Molecular basis of Body Integrity Identity Disorder

Body Identity Integrity Disorder (BIID) is a person*s intense and longstanding
desire to have one of several amputations of their limb(s). The main motivation
for amputation is not feeling complete with four limbs. BIID is an infrequently
described condition, is not included in DSM-IV-TR, and often not known to
surgeons, neurologist and psychiatrists. The etiology of the BIID remains
unclear, no genetic research to BIID has been done so far.

1. To make a phenomenological profile of BIID individuals using a standardized
questionnaire.
2. To perform whole exome analyses in four phenomenological identical BIID
individuals.
3. To perform molecular analyses in a series of other BIID individuals in case
a causative gene can be found by the total exome sequencing.

Questionnaire
After enrolment in the study the participants will be send a questionnaire in
order to gather all relevant information on their phenotype (Appendix 3).
Topics of the questions will be general demographics, medical history, family
history, BIID features and DSM-axis I screening. Questionnaires can be returned
either by ordinary mail or via a secured internet connection. Results of the
questionnaire will be computerized and statistically analyzed.

Blood sampling
Participants that have indicated to be willing to participate in the molecular
study will be sent a packet with materials and an instruction letter for blood
drawing. The blood can be drawn locally by their general physician or local
hospital. The instruction letter will not mention the term BIID. Materials
needed to return the samples by mail to Amsterdam for free will be added.

Molecular studies
Total exome sequencing using the 454 or Solid Genome Analyzer will be performed
in 4 BIID individuals. The choice of the participants will be made based on the
data from the questionnaire in order to ensure the highest possible homogeneity
within the group. The sequence capture technology from Ninblegen/Roche will be
used for the exome sequencing. DNA from the participants will be sheared,
hybridized to a set of oligonucleotides covering all exons of the human genome.
Eluted DNA will be sequenced on a massive parallel sequencer (454/Solid).
Bio-informatic analyses of the sequence information will be matched to the
human reference genome. The variations (sequence and structural) will be
compared with databases of known variation and prediction tools (SIFT,
Polyphen, splice site predictors) will be used to estimate the impact of the
variants. Variants will be ranked on predicted impact. Mutations in the same
gene in two or more participants will get the highest priority. Further total
exome sequencing in one or more additional participants will be performed if no
single gene can be detected. If the total exome sequencing leads to discovery
of a gene or of genes that are likely to be causative for BIID, Sanger
sequencing of these gene(s) will be repeated first in the four participants in
whom total exome sequencing was performed, and, if findings are confirmed, in
all other participants of whom DNA samples have become available for this
study.

The associated risks are restricted to blood draw in healthy individuals (apart
from their BIID). Because indivduals with BIID are highly secretive concerning
their BIID, the main burden of participation in this study could be the
disclosure of their BIID to the researchers.

With respect to the secretivity of the BIID individuals, the design of the
research has been made to protect the participants' identity as much as
possible. Communication and recruitment of the individuals will mainly be part
take part through the internet, which will give the participants enough time to
consider their participation.