Possibly relevant human trait(s) and/or gene(s) (MIM number): 612960 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive Lethal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2020

Species-specific symbol: cpp

History: Youngworth and Delany (2020): "The [cpp] mutation was first described under the name ectrodactyly (ec) and arose in a line carrying another autosomal recessive mutation named scaleless (sc). The homozygous sc mutation, as its name implies, results in absence of scales, as well as foot pads, spurs and most feather follicles, but otherwise does not cause craniofacial or limb defects. (Abbott & MacCabe 1966). The double sc/ec mutants were observed with these sc defects as well as an absent upper palate and abnormal hindlimbs (Abbott & MacCabe 1966). Outcrosses of the sc/ec carriers to normally feathered birds produced carriers who were test mated and then crossed to produce mutants with the palate abnormality alone to show that the mutations were unlinked (notably, the hindlimb abnormality occurred only in the double sc/ec mutants). The ec mutation was later backcrossed for nine generations into a highly inbred Single Comb White Leghorn line (UCD 003) and renamed cleft primary palate to reflect the key phenotype of the single mutation. The line was then closed to create the separate congenic inbred line UCD cpp.003, estimated to have greater than 99% DNA identity to UCD 003 outside of the introgressed mutation-encoding region given the number of backcrosses of the cpp-containing line to the highly inbred UCD 003 background line (Abplanalp 1992). Birds of the UCD cpp.003 line are test mated to verify carrier status prior to annual reproduction."

Inheritance: As summarised by Youngworth and Delany (2020), "The fact that carriers are phenotypically normal with consistent Mendelian ratios of mutants to carriers and non-carriers shows that the mutation is probably a recessive single-gene defect (Abbott & MacCabe 1966)."

Mapping: As summarised by Youngworth and Delany (2020), "The fact that carriers are phenotypically normal with consistent Mendelian ratios of mutants to carriers and non-carriers shows that the mutation is probably a recessive single-gene defect (Abbott & MacCabe 1966)."

Molecular basis: As summarised by Youngworth and Delany (2020), "The fact that carriers are phenotypically normal with consistent Mendelian ratios of mutants to carriers and non-carriers shows that the mutation is probably a recessive single-gene defect (Abbott & MacCabe 1966)."

Clinical features: Youngworth and Delany (2020): "The cpp mutation results in a severely abnormal frontonasal prominence, which gives the appearance of a recessed and upturned upper beak (see figure 4P‐T in Schock et al. 2016). This tissue defect appears to start with the abnormal fusion of facial prominences, coincident with and possibly owing to the absence of prefusion filaments in the mutants (Yee & Abbott 1978; Youngworth 2019). The cpp mutation ... is embryonic lethal between 17 and 20 days of incubation (Abbott & MacCabe 1966)."

Associated gene: