Expanding the phenotype of cerebellar-facial-dental syndrome: Two siblings with a novel variant in BRF1.
Abnormalities, Multiple
/ genetics
Cerebellum
/ abnormalities
Child
Craniofacial Abnormalities
/ genetics
Developmental Disabilities
/ genetics
Dwarfism
/ genetics
Humans
Infant
Intellectual Disability
/ genetics
Male
Muscular Atrophy
/ genetics
Mutation
Nervous System Malformations
/ genetics
Phenotype
Siblings
TATA-Binding Protein Associated Factors
/ genetics
Exome Sequencing
BRF1
cerebellofaciodental syndrome
growth retardation
microcephaly
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
22
04
2020
revised:
26
06
2020
accepted:
29
06
2020
pubmed:
9
9
2020
medline:
22
6
2021
entrez:
8
9
2020
Statut:
ppublish
Résumé
Cerebellofaciodental syndrome (MIM #616202) is an autosomal recessive condition characterized by intellectual disability, microcephaly, cerebellar hypoplasia, dysmorphic features, and short stature. To date, eight patients carrying biallelic BRF1 variants have been reported. Here, we describe two siblings with congenital microcephaly and corpus callosum hypoplasia, pre and postnatal growth retardation, congenital heart defect and severe global developmental delay. We also detected additional findings not previously reported in this syndrome, including bilateral sensorineural hearing impairment and inner ear malformation. Whole exome sequencing identified a novel homozygous missense variant (c.654G>C, p.[Trp218Cys]) in BRF1, predicted to affect the protein structure. Expression assessment showed extremely low BRF1 protein expression caused by the identified variant, supporting its causal involvement. The description of new patients with cerebellofaciodental syndrome is essential to better delineate the phenotypic and genotypic spectrum of the disease.
Identifiants
pubmed: 32896090
doi: 10.1002/ajmg.a.61839
doi:
Substances chimiques
BRF1 protein, human
0
TATA-Binding Protein Associated Factors
0
Types de publication
Case Reports
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2742-2745Informations de copyright
© 2020 Wiley Periodicals LLC.
Références
Akizu, N., Cantagrel, V., Schroth, J., Cai, N., Vaux, K., McCloskey, D., … Gleeson, J. G. (2013). AMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative brainstem disorder. Cell, 154(3), 505-517. https://doi.org/10.1016/j.cell.2013.07.005
Bellido, F., Sowada, N., Mur, P., Lázaro, C., Pons, T., Valdés-Mas, R., … Valle, L. (2018). Association between germline mutations in BRF1, a subunit of the RNA polymerase III transcription complex, and hereditary colorectal cancer. Gastroenterology, 154(1), 181-194. https://doi.org/10.1053/j.gastro.2017.09.005
Borck, G., Hög, F., Dentici, M. L., Tan, P. L., Sowada, N., Medeira, A., … Kubisch, C. (2015). BRF1 mutations alter RNA polymerase III-dependent transcription and cause neurodevelopmental anomalies. Genome Research, 25(2), 155-166. https://doi.org/10.1101/gr.176925.114
Cabarcas, S., & Schramm, L. (2011). RNA polymerase III transcription in cancer: The BRF2 connection. Molecular Cancer, 10, 47. https://doi.org/10.1186/1476-4598-10-47
Capriotti, E., Calabrese, R., & Casadio, R. (2006). Predicting the insurgence of human genetic diseases associated to single point protein mutations with support vector machines and evolutionary information. Bioinformatics, 22, 2729-2734. https://doi.org/10.1093/bioinformatics/btl423
Dieci, G., Conti, A., Pagano, A., & Carnevali, D. (2013). Identification of RNA polymerase III-transcribed genes in eukaryotic genomes. Biochimica et Biophysica Acta, 1829(3-4), 296-305. https://doi.org/10.1016/j.bbagrm.2012.09.010
Jee, Y. H., Sowada, N., Markello, T. C., Rezvani, I., Borck, G., & Baron, J. (2017). BRF1 mutations in a family with growth failure, markedly delayed bone age, and central nervous system anomalies. Clinical Genetics, 91(5), 739-747. https://doi.org/10.1111/cge.12887
Marshall, L., & White, R. J. (2008). Non-coding RNA production by RNA polymerase III is implicated in cancer. Nature Review Cancer, 8(12), 911-914. https://doi.org/10.1038/nrc2539
Namavar Y, Barth PG, Poll-The BT, Baas F. (2011). Classification, diagnosis and potential mechanisms in pontocerebellar hypoplasia. Orphanet Journal of Rare Diseases, 12(6), 50. https://doi.org/10.1186/1750-1172-6-50
Rudnik-Schöneborn, S., Barth, P. G., & Zerres, K. (2014). Pontocerebellar hypoplasia. American Journal of Medical Genetics C Seminars in Medical Genetics, 166C(2), 173-183. https://doi.org/10.1002/ajmg.c.31403
Schaffer, A. E., Eggens, V. R., Caglayan, A. O., Reuter, M. S., Scott, E., Coufal, N. G., … Gleeson, J. G. (2014). CLP1 founder mutation links tRNA splicing and maturation to cerebellar development and neurodegeneration. Cell, 157(3), 651-663. https://doi.org/10.1016/j.cell.2014.03.049
Schramm, L., Pendergrast, P. S., Sun, Y., & Hernandez, N. (2000). Different human TFIIIB activities direct RNA polymerase III transcription from TATA-containing and TATA-less promoters. Genes Development, 14(20), 2650-2663. https://doi.org/10.1101/gad.836400
White, R. J. (2011). Transcription by RNA polymerase III: More complex than we thought. Nature Reviews Genetics, 12(7), 459-463. https://doi.org/10.1038/nrg3001