EIF3F-related neurodevelopmental disorder: refining the phenotypic and expanding the molecular spectrum

Hüffmeier U, Kraus C, Reuter M, Uebe S, Abbott MA, Ahmed SA, Rawson KL, Barr E, Li H, Bruel AL, Faivre L, Mau-Them FT, Botti C, Brooks S, Burns K, Ward DI, Dutra-Clarke M, Martinez-Agosto JA, Lee H, Nelson SF, Zacher P, Abou Jamra R, Kloeckner C, Mcgaughran J, Kohlhase J, Schuhmann S, Moran E, Pappas J, Raas-Rothschild A, Sacoto MJG, Henderson LB, Palculict TB, Mullegama S, Elloumi HZ, Reich A, Vergano SAS, Wahl E, Reis A, Zweier C (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 16

Article Number: 136

Journal Issue: 1

DOI: 10.1186/s13023-021-01744-1

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.

Authors with CRIS profile

Involved external institutions

University of California Los Angeles (UCLA) United States (USA) (US) Sanford Health United States (USA) (US) Universität Leipzig Germany (DE) Royal Brisbane and Women's Hospital Australia (AU) Kaiser Permanente United States (USA) (US) Université Bourgogne Franche-Comté France (FR) GeneDX United States (USA) (US) Tel Aviv University Israel (IL) University at Buffalo. State University of New York United States (USA) (US) New York University (NYU) United States (USA) (US) Children's Hospital of The King's Daughters United Kingdom (GB) Emory University United States (USA) (US) University of Massachusetts Amherst (UMass) United States (USA) (US) The State University of New Jersey (Rutgers) United States (USA) (US) SYNLAB MVZ Humangenetik Freiburg GmbH Germany (DE)

How to cite

APA:

Hüffmeier, U., Kraus, C., Reuter, M., Uebe, S., Abbott, M.-A., Ahmed, S.A.,... Zweier, C. (2021). EIF3F-related neurodevelopmental disorder: refining the phenotypic and expanding the molecular spectrum. Orphanet Journal of Rare Diseases, 16(1). https://doi.org/10.1186/s13023-021-01744-1

MLA:

Hüffmeier, Ulrike, et al. "EIF3F-related neurodevelopmental disorder: refining the phenotypic and expanding the molecular spectrum." Orphanet Journal of Rare Diseases 16.1 (2021).

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