11, 2002, Gazette)
Photo by HSIMSHong Zheng, (front) a visiting scholar
from Hunan Medical University, Zhengzhou, China, is working on mild hemophilia
A research with Dr. Yangyang Xie, director of the Molecular Genetics Laboratory.
Dr. Yangyang Xie is a quiet man with an intense devotion to his work as
a molecular geneticist. He has good reason to be proud of what hes
accomplished since arriving in St. Johns in 1998 to accept a position
as director of the Molecular Genetics Lab and a faculty member in medicine.
After just a years search, he was instrumental in identifying the
genetic mutation for mild hemophilia A in a central Newfoundland population.
Hemophilia A is a bleeding disorder characterized by easy bruising, nosebleeds,
bleeding into muscles and joints, delayed bleeding after surgery or dental
extraction, and sometimes internal bleeding. Some carrier women are known
to have a bleeding tendency as well, such as heavy periods or post-partum
The high incidence of hemophilia A in central Newfoundland has long been
known, and unfortunately attracted the attention of outside researchers
who came in and took blood samples, but never produced any results. The
local residents and physicians were angry and refused contact with the
Health Care Corporation, even though it was not that organization that
took the samples, explained Dr. Xie. So when we went to investigate
the disease we had to win over the community.
From the beginning, Dr. Xie committed himself to presenting research results
every six months. I told people there that we are a Newfoundland
team and we would convert our research findings into clinical services.
Together with hematologist Dr. Mary Frances Scully, genetic counselor
David MacGregor, nurse co-ordinator Marilyn Harvey, and other support
staff, that promise has been kept.
Finding the actual gene mutation for the Newfoundland variation of hemophilia
A began with the hypothesis that it would be a mild mutation resulting
in either reduced or abnormal gene product. We also speculated that
because of the high prevalence of hemophilia it was due to the founders
effect and the isolated geography of the region, said Dr. Xie, who
worked on identifying the gene mutation in collaboration with Dr. David
Lillicrap at Queens University, Kingston. A founder effect
of the identified mutation has been proved, which explains the higher
prevalence of mild hemophilia A in Newfoundland.
Based on the molecular nature of the identified mutation, Dr. Xies
team established a simple and quick direct mutation test. The direct
mutation test has been offered as clinical service for the entire province.
This enables us to make an early diagnosis for pre-symptomatic patients
so that they can have early medical measures to minimize the long-term
complications. It also provides a precise diagnosis for atypical patients
and allows us to determine the carrier status of women in this population
and offer a prenatal diagnosis service in the future.
The high prevalence of mild hemophila A means about 44 of the 3,300 males
in the region have the disease, the highest known population density in
the world. Women generally do not have symptoms, but if they have the
gene mutation they may pass it on to their children. Clinical histories
and genetic counseling have been provided for the families with affected
individuals, and family histories from these patients plus a mutation
test enabled Dr. Xie and the other researchers to link all affected individuals
to one very large kindred comprising more than 1,630 family members spanning
The population screening for the mild hemophilia A mutation had one unexpected
result. We identified another isolated population with extremely
high prevalence of mild hemophilia A from rural Labrador, about 14 in
260 males. Patients from this population do not carry the mutation identified
in the central Newfoundland area, so it suggests another possible causative
founder effect for mild hemophilia in this province. Dr. Xie has
obtained the research funding from the Janeway Research Foundation for
a study on the molecular defect of the mild hemophilia identified from
the Labrador area.
Financial support for the research on mild hemophilia A in the central
Newfoundland area was provided by the Aventis-Behring Canada Research
Fund, the Janeway Research Foundation and the Faculty of Medicine. Dr.
Xie was recently awarded $100,000 over two years from the Canadian Hemophilia
Society for further scientific research.