Segregation analysis of cleft lip with or without cleft palate in the First Nations (Amerindian) people of British Columbia and review of isolated cleft palate etiologies.
BACKGROUND
The First Nations (Amerindian) population of British Columbia, Canada, has the highest reported birth prevalence in the world of cleft lip with or without cleft palate (CL/P) at nearly 3 per 1000 births. In addition, a substantial proportion of cleft palate only (CPO) cases in this population has been reported to be X-linked. The aims of this study were to perform complex segregation analysis to investigate the mode of inheritance of CL/P in the First Nations people of British Columbia and to review the etiology of the CPO cases.


METHODS
All First Nations children born in British Columbia between 1952 and 1971 with an orofacial cleft were included in the study. Multiple sources of ascertainment were used, so that nearly 100% of live births were identified and included during this time. No stillbirths were found but would likely have been ascertained. Extended pedigrees were constructed from these probands and examination of immediate family members, e.g., parents and siblings, was done wherever possible. Complex segregation analysis included all family members. In addition, a CPO case review was conducted.


RESULTS
Complex segregation analysis supports the hypothesis that the most likely mode of inheritance of CL/P in this population is a mixed model; that is, an autosomal major gene with polygenic component. The review of 26 CPO cases showed that a substantial proportion are syndromic.
Lowry
R Brian
RB
Department of Clinical Genetics, Alberta Children's Hospital, 2888 Shaganappi Trail NW, Calgary, AB, T3B 6A8, Canada. brian.lowry@calgaryhealthregion.ca
Johnson
Candice Y
CY
Gagnon
France
F
Little
Julian
J
D001955:British Columbia / Q000453:epidemiology / Q000208:ethnology; D002971:Cleft Lip / Q000453:epidemiology / Q000235:genetics*; D002972:Cleft Palate / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D040181:Genetic Diseases, X-Linked / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007198:Indians, North American / Q000208:ethnology / Q000235:genetics*; D008297:Male