Search

Your search keyword '"Sakkubai, N."' showing total 5 results
Start Over Author "Sakkubai, N."
5 results on '"Sakkubai, N."'

1. Expanding the Spectrum of BAF-Related Disorders: De Novo Variants in SMARCC2 Cause a Syndrome with Intellectual Disability and Developmental Delay

Author

Machol, K., Rousseau, J., Ehresmann, S., Garcia, T., Nguyen, T.T.M., Spillmann, R.C., Sullivan, J.A., Shashi, V., Jiang, Y.H., Stong, N., Fiala, E., Willing, M., Pfundt, R.P., Kleefstra, T., Cho, M.T., McLaughlin, H., Piera, M. Rosello, Orellana, C., Martinez, F., Caro-Llopis, A., Monfort, S., Roscioli, T., Nixon, C.Y., Buckley, M.F., Turner, A., Jones, W.D., Hasselt, P.M. van, Hofstede, F.C., Gassen, K.L.I. van, Brooks, A.S., Slegtenhorst, M.A. van, Lachlan, K., Sebastian, J., Madan-Khetarpal, S., Sonal, D., Sakkubai, N., Thevenon, J., Faivre, L., Maurel, A., Petrovski, S., Krantz, I.D., Tarpinian, J.M., Rosenfeld, J.A., Lee, B.H., Campeau, P.M., Machol, K., Rousseau, J., Ehresmann, S., Garcia, T., Nguyen, T.T.M., Spillmann, R.C., Sullivan, J.A., Shashi, V., Jiang, Y.H., Stong, N., Fiala, E., Willing, M., Pfundt, R.P., Kleefstra, T., Cho, M.T., McLaughlin, H., Piera, M. Rosello, Orellana, C., Martinez, F., Caro-Llopis, A., Monfort, S., Roscioli, T., Nixon, C.Y., Buckley, M.F., Turner, A., Jones, W.D., Hasselt, P.M. van, Hofstede, F.C., Gassen, K.L.I. van, Brooks, A.S., Slegtenhorst, M.A. van, Lachlan, K., Sebastian, J., Madan-Khetarpal, S., Sonal, D., Sakkubai, N., Thevenon, J., Faivre, L., Maurel, A., Petrovski, S., Krantz, I.D., Tarpinian, J.M., Rosenfeld, J.A., Lee, B.H., and Campeau, P.M.

Abstract

Contains fulltext : 202800.pdf (publisher's version ) (Open Access), SMARCC2 (BAF170) is one of the invariable core subunits of the ATP-dependent chromatin remodeling BAF (BRG1-associated factor) complex and plays a crucial role in embryogenesis and corticogenesis. Pathogenic variants in genes encoding other components of the BAF complex have been associated with intellectual disability syndromes. Despite its significant biological role, variants in SMARCC2 have not been directly associated with human disease previously. Using whole-exome sequencing and a web-based gene-matching program, we identified 15 individuals with variable degrees of neurodevelopmental delay and growth retardation harboring one of 13 heterozygous variants in SMARCC2, most of them novel and proven de novo. The clinical presentation overlaps with intellectual disability syndromes associated with other BAF subunits, such as Coffin-Siris and Nicolaides-Baraitser syndromes and includes prominent speech impairment, hypotonia, feeding difficulties, behavioral abnormalities, and dysmorphic features such as hypertrichosis, thick eyebrows, thin upper lip vermilion, and upturned nose. Nine out of the fifteen individuals harbor variants in the highly conserved SMARCC2 DNA-interacting domains (SANT and SWIRM) and present with a more severe phenotype. Two of these individuals present cardiac abnormalities. Transcriptomic analysis of fibroblasts from affected individuals highlights a group of differentially expressed genes with possible roles in regulation of neuronal development and function, namely H19, SCRG1, RELN, and CACNB4. Our findings suggest a novel SMARCC2-related syndrome that overlaps with neurodevelopmental disorders associated with variants in BAF-complex subunits.

Published
2019

2. Rett Syndrome

Author

Hoffman, E. P., primary, Sirianni, N., additional, Pereira, J. L., additional, Pillotto, R. F., additional, and Sakkubai, N., additional

Published
1998
Full Text
View/download PDF

4. Chromosome mapping of Rett syndrome: a likely candidate region on the telomere of Xq

Author

Hansmann, I., Xiang, F., Zhang, Z., Anvret, M., Edström, L., Clarke, A., Joseluiz, P., Sakkubai, N., Sarojini, B., and delozier-Blanchet, C.D.

Abstract

Rett syndrome (RS) is a disease of neurological development. First reported 30 years ago in 1966, its biological and genetic basis remains obscure. RS is commonly thought of as an X linked dominant disorder lethal to hemizygous males. The few familial cases would arise through mosaicism or because of occasional females failing to manifest the disorder through skewed X inactivation in relevant cell types. We have one family where the mother and daughter are affected with RS, and which can be explained according to this hypothesis. If the alternative proposal of Thomas (1996) is correct, that the lack of males affected by such disorders is the result of a high male to female ratio of germline mutations rather than of gestational lethality, then the RS gene should be located on the grandpaternal chromosome. Genomic screening with markers covering the whole X chromosome has been performed. Studies using multiple informative markers indicate that the RS locus is likely to be located close to one of the X chromosome telomeres. Further investigations in eight additional families suggest the most likely region for the RS gene to be is the distal part of Xq (Xq28).

Published
1998

5. Expanding the Spectrum of BAF-Related Disorders: De Novo Variants in SMARCC2 Cause a Syndrome with Intellectual Disability and Developmental Delay.

Author

Machol K, Rousseau J, Ehresmann S, Garcia T, Nguyen TTM, Spillmann RC, Sullivan JA, Shashi V, Jiang YH, Stong N, Fiala E, Willing M, Pfundt R, Kleefstra T, Cho MT, McLaughlin H, Rosello Piera M, Orellana C, Martínez F, Caro-Llopis A, Monfort S, Roscioli T, Nixon CY, Buckley MF, Turner A, Jones WD, van Hasselt PM, Hofstede FC, van Gassen KLI, Brooks AS, van Slegtenhorst MA, Lachlan K, Sebastian J, Madan-Khetarpal S, Sonal D, Sakkubai N, Thevenon J, Faivre L, Maurel A, Petrovski S, Krantz ID, Tarpinian JM, Rosenfeld JA, Lee BH, and Campeau PM

Subjects
Abnormalities, Multiple genetics, Adolescent, Child, Child, Preschool, DNA-Binding Proteins, Face abnormalities, Female, Hand Deformities, Congenital genetics, Humans, Male, Micrognathism genetics, Neck abnormalities, Reelin Protein, Syndrome, Developmental Disabilities complications, Developmental Disabilities genetics, Intellectual Disability complications, Intellectual Disability genetics, Mutation, Transcription Factors genetics
Abstract

SMARCC2 (BAF170) is one of the invariable core subunits of the ATP-dependent chromatin remodeling BAF (BRG1-associated factor) complex and plays a crucial role in embryogenesis and corticogenesis. Pathogenic variants in genes encoding other components of the BAF complex have been associated with intellectual disability syndromes. Despite its significant biological role, variants in SMARCC2 have not been directly associated with human disease previously. Using whole-exome sequencing and a web-based gene-matching program, we identified 15 individuals with variable degrees of neurodevelopmental delay and growth retardation harboring one of 13 heterozygous variants in SMARCC2, most of them novel and proven de novo. The clinical presentation overlaps with intellectual disability syndromes associated with other BAF subunits, such as Coffin-Siris and Nicolaides-Baraitser syndromes and includes prominent speech impairment, hypotonia, feeding difficulties, behavioral abnormalities, and dysmorphic features such as hypertrichosis, thick eyebrows, thin upper lip vermilion, and upturned nose. Nine out of the fifteen individuals harbor variants in the highly conserved SMARCC2 DNA-interacting domains (SANT and SWIRM) and present with a more severe phenotype. Two of these individuals present cardiac abnormalities. Transcriptomic analysis of fibroblasts from affected individuals highlights a group of differentially expressed genes with possible roles in regulation of neuronal development and function, namely H19, SCRG1, RELN, and CACNB4. Our findings suggest a novel SMARCC2-related syndrome that overlaps with neurodevelopmental disorders associated with variants in BAF-complex subunits., (Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Published
2019
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results