| Autor: |
Ulrike Hüffmeier, Cornelia Kraus, Miriam S. Reuter, Steffen Uebe, Mary-Alice Abbott, Syed A. Ahmed, Kristyn L. Rawson, Eileen Barr, Hong Li, Ange-Line Bruel, Laurence Faivre, Frédéric Tran Mau-Them, Christina Botti, Susan Brooks, Kaitlyn Burns, D. Isum Ward, Marina Dutra-Clarke, Julian A. Martinez-Agosto, Hane Lee, Stanley F. Nelson, UCLA California Center for Rare Disease, Pia Zacher, Rami Abou Jamra, Chiara Klöckner, Julie McGaughran, Jürgen Kohlhase, Sarah Schuhmann, Ellen Moran, John Pappas, Annick Raas-Rothschild, Maria J. Guillen Sacoto, Lindsay B. Henderson, Timothy Blake Palculict, Sureni V. Mullegama, Houda Zghal Elloumi, Adi Reich, Samantha A. Schrier Vergano, Erica Wahl, André Reis, Christiane Zweier |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Orphanet Journal of Rare Diseases, Vol 16, Iss 1, Pp 1-9 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
1750-1172 |
| DOI: |
10.1186/s13023-021-01744-1 |
| Popis: |
Abstract Background An identical homozygous missense variant in EIF3F, identified through a large-scale genome-wide sequencing approach, was reported as causative in nine individuals with a neurodevelopmental disorder, characterized by variable intellectual disability, epilepsy, behavioral problems and sensorineural hearing-loss. To refine the phenotypic and molecular spectrum of EIF3F-related neurodevelopmental disorder, we examined independent patients. Results 21 patients were homozygous and one compound heterozygous for c.694T>G/p.(Phe232Val) in EIF3F. Haplotype analyses in 15 families suggested that c.694T>G/p.(Phe232Val) was a founder variant. All affected individuals had developmental delays including delayed speech development. About half of the affected individuals had behavioral problems, altered muscular tone, hearing loss, and short stature. Moreover, this study suggests that microcephaly, reduced sensitivity to pain, cleft lip/palate, gastrointestinal symptoms and ophthalmological symptoms are part of the phenotypic spectrum. Minor dysmorphic features were observed, although neither the individuals’ facial nor general appearance were obviously distinctive. Symptoms in the compound heterozygous individual with an additional truncating variant were at the severe end of the spectrum in regard to motor milestones, speech delay, organic problems and pre- and postnatal growth of body and head, suggesting some genotype–phenotype correlation. Conclusions Our study refines the phenotypic and expands the molecular spectrum of EIF3F-related syndromic neurodevelopmental disorder. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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