Genetic analysis of cleft lip with or without cleft palate in Chinese kindreds

Cleft lip with or without cleft palate (CL +/- P) affects 1 in 500-1,000 newborns worldwide; the cause remains unclear. For CL +/- P, Asians are at higher risk than Caucasians or Blacks. This report presents the results of a genetic analysis of 163 CL +/- P proband families ascertained in Shanghai, China. Based on statistical tests of several predictions from the classical multifactorial/threshold model, no evidence could be found to support it. Further, goodness-of-fit (PGOODFIT) tests of this model were also unsupportive, there being more families with two or more affected sibs than expected. Classical segregation analysis for Mendelian inheritance showed a maximum likelihood estimate of the segregation ratio of 0.187 +/- 0.068. This value was not significantly less than 0.25 (recessive inheritance) but was significantly less than 0.50 (dominant inheritance). Sex ratio data from these Chinese families suggest that manifestation of the putative single major gene is sex influenced. The apparent reduced penetrance is likewise to be expected if manifestation of CL +/- P also depends on in utero exposure to deleterious environmental agents, as demonstrated in a variety of human and animal model studies.