@article{ce34ba748f0440ff8a300691c25ba2a8,
title = "FAT4 identified as a potential modifier of orofacial cleft laterality",
abstract = "Orofacial clefts (OFCs) are common (1 in 700 births) congenital malformations that include a cleft lip (CL) and cleft lip and palate (CLP). These OFC subtypes are also heterogeneous themselves, with the CL occurring on the left, right, or both sides of the upper lip. Unilateral CL and CLP have a 2:1 bias towards left-sided clefts, suggesting a nonrandom process. Here, we performed a study of left- and right-sided clefts within the CL and CLP subtypes to better understand the genetic factors controlling cleft laterality. We conducted genome-wide modifier analyses by comparing cases that had right unilateral CL (RCL; N = 130), left unilateral CL (LCL; N = 216), right unilateral CLP (RCLP; N = 416), or left unilateral CLP (LCLP; N = 638), and identified a candidate region on 4q28, 400 kb downstream from FAT4, that approached genome-wide significance for LCL versus RCL (p = 8.4 × 10−8). Consistent with its potential involvement as a genetic modifier of CL, we found that Fat4 exhibits a specific domain of expression in the mesenchyme of the medial nasal processes that form the median upper lip. Overall, these results suggest that the epidemiological similarities in left- to right-sided clefts in CL and CLP are not reflected in the genetic association results.",
keywords = "birth defect, cleft lip, cleft lip and palate, genetic modifier, genotype–phenotype, left cleft lip, right cleft lip",
author = "Curtis, {Sarah W.} and Daniel Chang and Sun, {Miranda R.} and Epstein, {Michael P.} and Murray, {Jeffrey C.} and Eleanor Feingold and Beaty, {Terri H.} and Weinberg, {Seth M.} and Marazita, {Mary L.} and Lipinski, {Robert J.} and Carlson, {Jenna C.} and Leslie, {Elizabeth J.}",
note = "Funding Information: The authors thank the dedicated field staff, collaborators, and participating families for their important contributions to this study. This study was supported by grants from the National Institutes of Health (NIH) including R00-DE025060 [E. J. L.], X01-HG007485 [M. L. M. and E. F.], R01-DE016148 [M. L. M. and S. M. W.], U01-DE024425 [M. L. M.], R37-DE008559 [J. C. M. and M. L. M.], R01-DE009886 [M. L. M.], R21-DE016930 [M. L. M.], R01-DE012472 [M. L. M.], R01-DE014581 [T. B.], U01-DE018993 [T. B.]. Funding for genotyping by the National Human Genome Research Institute (X01-HG007821) and funding for initial genomic data cleaning by the University of Washington provided by contract HHSN268201200008I from the National Institute for Dental and Craniofacial Research awarded to the Center for Inherited Disease Research. Funding Information: The authors thank the dedicated field staff, collaborators, and participating families for their important contributions to this study. This study was supported by grants from the National Institutes of Health (NIH) including R00‐DE025060 [E. J. L.], X01‐HG007485 [M. L. M. and E. F.], R01‐DE016148 [M. L. M. and S. M. W.], U01‐DE024425 [M. L. M.], R37‐DE008559 [J. C. M. and M. L. M.], R01‐DE009886 [M. L. M.], R21‐DE016930 [M. L. M.], R01‐DE012472 [M. L. M.], R01‐DE014581 [T. B.], U01‐DE018993 [T. B.]. Funding for genotyping by the National Human Genome Research Institute (X01‐HG007821) and funding for initial genomic data cleaning by the University of Washington provided by contract HHSN268201200008I from the National Institute for Dental and Craniofacial Research awarded to the Center for Inherited Disease Research. Publisher Copyright: {\textcopyright} 2021 Wiley Periodicals LLC",
year = "2021",
month = oct,
doi = "10.1002/gepi.22420",
language = "English (US)",
volume = "45",
pages = "721--735",
journal = "Genetic epidemiology",
issn = "0741-0395",
publisher = "Wiley-Liss Inc.",
number = "7",
}