Heterozygous loss-of-function variants of MEIS2 cause a triad of palatal defects, congenital heart defects, and intellectual disability

Autor: Verheije, R., Kupchik, G.S., Isidor, B., Kroes, H.Y., Lynch, S.A., Hawkes, L., Hempel, M., Gelb, B.D., Ghoumid, J., D’Amours, G., Chandler, K., Dubourg, C., Loddo, S., Tümer, Z., Shaw-Smith, C., Nizon, M., Shevell, M., Van Hoof, E., Anyane-Yeboa, K., Cerbone, G., Clayton-Smith, J., Cogné, B., Corre, P., Corveleyn, A., De Borre, M., Hjortshøj, T.D., Fradin, M., Gewillig, M., Goldmuntz, E., Hens, G., Lemyre, E., Journel, H., Kini, U., Kortüm, F., Le Caignec, C., Novelli, A., Odent, S., Petit, F., Revah-Politi, A., Stong, N., Strom, T.M., van Binsbergen, E., DDD Study, Devriendt, K., Breckpot, J.
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
Loss of Function Mutation
Intellectual disability
Genetics(clinical)
Non-U.S. Gov't
Child
Genetics (clinical)
Heart Defects
Genetics
0303 health sciences
Congenital/genetics
Research Support
Non-U.S. Gov't
030305 genetics & heredity
Syndrome
Phenotype
Heart Defects
Congenital/genetics
Cleft Palate
Child
Preschool
Female
Haploinsufficiency
Heart Defects
Congenital
Heterozygote
Adolescent
Transcription Factors/genetics
Locus (genetics)
Research Support
Article
N.I.H
03 medical and health sciences
Young Adult
Research Support
N.I.H.
Extramural
Cleft Palate/genetics
Intellectual Disability
medicine
Journal Article
Humans
Preschool
Gene
Loss function
Homeodomain Proteins
business.industry
Chromosome
Extramural
Heterozygote advantage
medicine.disease
Intellectual Disability/genetics
Homeodomain Proteins/genetics
business
Transcription Factors
Zdroj: Verheije, R, Kupchik, G S, Isidor, B, Kroes, H Y, Lynch, S A, Hawkes, L, Hempel, M, Gelb, B D, Ghoumid, J, D’amours, G, Chandler, K, Dubourg, C, Loddo, S, Tümer, Z, Shaw-smith, C, Nizon, M, Shevell, M, Van Hoof, E, Anyane-yeboa, K, Cerbone, G, Clayton-smith, J, Cogné, B, Corre, P, Corveleyn, A, De Borre, M, Hjortshøj, T D, Fradin, M, Gewillig, M, Goldmuntz, E, Hens, G, Lemyre, E, Journel, H, Kini, U, Kortüm, F, Le Caignec, C, Novelli, A, Odent, S, Petit, F, Revah-politi, A, Stong, N, Strom, T M, Van Binsbergen, E, Devriendt, K & Breckpot, J 2019, ' Heterozygous loss-of-function variants of MEIS2 cause a triad of palatal defects, congenital heart defects, and intellectual disability ', European Journal of Human Genetics, vol. 27, no. 2, pp. 278-290 . https://doi.org/10.1038/s41431-018-0281-5
European Journal of Human Genetics, 27(2), 278. Nature Publishing Group
Eur. J. Hum. Genet. 27, 278-290 (2019)
ISSN: 1018-4813
DOI: 10.1038/s41431-018-0281-5
Popis: Deletions on chromosome 15q14 are a known chromosomal cause of cleft palate, typically co-occurring with intellectual disability, facial dysmorphism, and congenital heart defects. The identification of patients with loss-of-function variants in MEIS2, a gene within this deletion, suggests that these features are attributed to haploinsufficiency of MEIS2. To further delineate the phenotypic spectrum of the MEIS2-related syndrome, we collected 23 previously unreported patients with either a de novo sequence variant in MEIS2 (9 patients), or a 15q14 microdeletion affecting MEIS2 (14 patients). All but one de novo MEIS2 variant were identified by whole-exome sequencing. One variant was found by targeted sequencing of MEIS2 in a girl with a clinical suspicion of this syndrome. In addition to the triad of palatal defects, heart defects, and developmental delay, heterozygous loss of MEIS2 results in recurrent facial features, including thin and arched eyebrows, short alae nasi, and thin vermillion. Genotype–phenotype comparison between patients with 15q14 deletions and patients with sequence variants or intragenic deletions within MEIS2, showed a higher prevalence of moderate-to-severe intellectual disability in the former group, advocating for an independent locus for psychomotor development neighboring MEIS2.
Databáze: OpenAIRE
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