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

Hüffmeier, Ulrike; Kraus, Cornelia; Reuter, Miriam S; Uebe, Steffen; Abbott, Mary-Alice; Ahmed, Syed A; Rawson, Kristyn L; Barr, Eileen; Li, Hong; Bruel, Ange-Line; Faivre, Laurence; Tran Mau-Them, Frédéric; Botti, Christina; Brooks, Susan; Burns, Kaitlyn; Ward, D Isum; Dutra-Clarke, Marina; Martinez-Agosto, Julian A; Lee, Hane; Nelson, Stanley F; ... (2021). EIF3F-related neurodevelopmental disorder: refining the phenotypic and expanding the molecular spectrum. Orphanet journal of rare diseases, 16(1), p. 136. BioMed Central 10.1186/s13023-021-01744-1

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinics of Human Genetics

UniBE Contributor:

Zweier, Christiane Gertrud

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1750-1172

Publisher:

BioMed Central

Language:

English

Submitter:

André Schaller

Date Deposited:

23 Dec 2021 08:27

Last Modified:

26 Dec 2021 01:48

Publisher DOI:

10.1186/s13023-021-01744-1

PubMed ID:

33736665

Uncontrolled Keywords:

Altered muscular tone Behavioral difficulties Deafness EIF3F gene Neurodevelopmental disorder Short stature

BORIS DOI:

10.48350/162638

URI:

https://boris.unibe.ch/id/eprint/162638

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