A study of the complex genetics of brain development has been undertaken with an emphasis on those genes that cause the most common structural forebrain anomaly in humans, holoprosencephaly (HPE). This malformation of the brain can result from either environmental or genetic causes. It is the aim of these investigations to determine the genes responsible for both normal and abnormal brain development through the study of patients with this disorder. Mutations in six such genes has been shown by us to be responsible for approximately one quarter of familial and sporadic cases of HPE (Roessler et al. 1996,1997;Brown et al., 1998;Wallis et al., 1999;Gripp et al., 2000;Ming et al., 2002;dela Cruz et al., 2002). Other genes either related to the hedgehog pathway or located at defined genetic loci may also contribute to HPE and are the subject of active investigation. We anticipate that many genes important for normal brain development will be identified in the search for genetic causes of HPE. In addition, the aim of these investigations is to identify environmental factors that contribute to HPE. Animal models have shown that low maternal cholesterol causes brain anomalies in some offspring. The findings are now being tested in epidemiological studies where low maternal serum cholesterol during pregnancy is correlated with birth outcome.

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National Human Genome Research Institute
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Paththinige, C S; Sirisena, N D; Kariyawasam, U G I U et al. (2018) A child with multiple congenital anomalies due to partial trisomy 7q22.1???qter resulting from a maternally inherited balanced translocation: a case report and review of literature. BMC Med Genomics 11:44
Kruszka, Paul; Solomon, Benjamin D; Muenke, Maximilian (2018) Introduction. Am J Med Genet C Semin Med Genet 178:113-116
Solomon, Benjamin D; Kruszka, Paul; Muenke, Maximilian (2018) Holoprosencephaly flashcards: An updated summary for the clinician. Am J Med Genet C Semin Med Genet 178:117-121
Martinez, Ariel F; Kruszka, Paul S; Muenke, Maximilian (2018) Extracephalic manifestations of nonchromosomal, nonsyndromic holoprosencephaly. Am J Med Genet C Semin Med Genet 178:246-257
Kruszka, Paul; Martinez, Ariel F; Muenke, Maximilian (2018) Molecular testing in holoprosencephaly. Am J Med Genet C Semin Med Genet 178:187-193
Roessler, Erich; Hu, Ping; Muenke, Maximilian (2018) Holoprosencephaly in the genomics era. Am J Med Genet C Semin Med Genet 178:165-174
Kruszka, Paul; Muenke, Maximilian (2018) Syndromes associated with holoprosencephaly. Am J Med Genet C Semin Med Genet 178:229-237
Hong, Sungkook; Hu, Ping; Roessler, Erich et al. (2018) Loss-of-function mutations in FGF8 can be independent risk factors for holoprosencephaly. Hum Mol Genet 27:1989-1998
Hadley, Donald W; Kruszka, Paul; Muenke, Maximilian (2018) Challenging issues arising in counseling families experiencing holoprosencephaly. Am J Med Genet C Semin Med Genet 178:238-245
Roessler, Erich; Hu, Ping; Marino, Juliana et al. (2018) Common genetic causes of holoprosencephaly are limited to a small set of evolutionarily conserved driver genes of midline development coordinated by TGF-?, hedgehog, and FGF signaling. Hum Mutat 39:1416-1427

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