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

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; 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; UCLA California Center for Rare Disease

doi:10.1186/s13023-021-01744-1

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

Journal article

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

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, …

Orphanet journal of rare diseases, Vol.16(1), pp.136-136

03/18/2021

DOI: https://doi.org/10.1186/s13023-021-01744-1

PMID: 33736665

Abstract

Short stature

Deafness

Behavioral difficulties

Neurodevelopmental disorder

EIF3F gene

Altered muscular tone

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. 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. Our study refines the phenotypic and expands the molecular spectrum of EIF3F-related syndromic neurodevelopmental disorder.

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Title: EIF3F-related neurodevelopmental disorder: refining the phenotypic and expanding the molecular spectrum
Creators: Ulrike Hüffmeier - Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 10, 91054, Erlangen, Germany. ulrike.hueffmeier@uk-erlangen.de
Cornelia Kraus - Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 10, 91054, Erlangen, Germany
Miriam S Reuter - Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 10, 91054, Erlangen, Germany
Steffen Uebe - Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 10, 91054, Erlangen, Germany
Mary-Alice Abbott - Medical Genetics, Department of Pediatrics, University of Massachusetts Medical School - Baystate, Springfield, MA, USA
Syed A Ahmed - Department of Genetics, Southern California Permanente Medical Group, Kaiser Permanente, Riverside, CA, USA
Kristyn L Rawson - Department of Genetics, Southern California Permanente Medical Group, Kaiser Permanente, Riverside, CA, USA
Eileen Barr - Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA
Hong Li - Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA
Ange-Line Bruel - Laboratoire de Génétique Chromosomique et Moléculaire, UF Innovation en diagnostic génomique des maladies rares, Plateau de Biologie Hospitalo-Universitaire, Centre Hospitalier Universitaire de Dijon, Dijon, France
Laurence Faivre - Centre de Génétique, Centre de Référence «Anomalies du Développement et Syndromes Malformatifs» et FHU TRANSLAD, Hôpital D'Enfants, Centre Hospitalier Universitaire de Dijon, Dijon, France
Frédéric Tran Mau-Them - Laboratoire de Génétique Chromosomique et Moléculaire, UF Innovation en diagnostic génomique des maladies rares, Plateau de Biologie Hospitalo-Universitaire, Centre Hospitalier Universitaire de Dijon, Dijon, France
Christina Botti - Division of Medical Genetics, Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, 08901, USA
Susan Brooks - Division of Medical Genetics, Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, 08901, USA
Kaitlyn Burns - Sanford Health, Sioux Falls, SD, USA
D Isum Ward - Sanford Health, Sioux Falls, SD, USA
Marina Dutra-Clarke - Division of Genetics, Department of Pediatrics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA
Julian A Martinez-Agosto - Department of Human Genetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA
Hane Lee - Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA
Stanley F Nelson - Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, 90095, USA
Pia Zacher - Epilepsy Center Kleinwachau, Radeberg, Germany
Rami Abou Jamra - Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany
Chiara Klöckner - Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany
Julie McGaughran - School of Medicine, The University of Queensland, St Lucia, Brisbane, Australia
Jürgen Kohlhase - Synlab Human Genetics Freiburg, Freiburg, Germany
Sarah Schuhmann - Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 10, 91054, Erlangen, Germany
Ellen Moran - Clinical Genetics, Hassenfeld Children's Hospital at NYU Langone, NYU Langone, Orthopedic Hospital, New York, NY, USA
John Pappas - Division of Clinical Genetic Services, Department of Pediatrics, NYU Grossman School of Medicine, New York, NY, USA
Annick Raas-Rothschild - Institute of Rare Diseases, Edmond & Lily Safra Children Hospital, Tel Hashomer, Israel
Maria J Guillen Sacoto - GeneDx, Gaithersburg, MD, 20877, USA
Lindsay B Henderson - GeneDx, Gaithersburg, MD, 20877, USA
Timothy Blake Palculict - GeneDx, Gaithersburg, MD, 20877, USA
Sureni V Mullegama - GeneDx, Gaithersburg, MD, 20877, USA
Houda Zghal Elloumi - GeneDx, Gaithersburg, MD, 20877, USA
Adi Reich - GeneDx, Gaithersburg, MD, 20877, USA
Samantha A Schrier Vergano - Division of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, VA, USA
Erica Wahl - Division of Genetics, UBMD Pediatrics, Buffalo, NY, USA
André Reis - Institute of Human Genetics, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Schwabachanlage 10, 91054, Erlangen, Germany
Christiane Zweier - Department of Human Genetics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
UCLA California Center for Rare Disease
Publication Details: Orphanet journal of rare diseases, Vol.16(1), pp.136-136
Date published: 03/18/2021
Grant note: UL1 TR001881 / NCATS NIH HHS
Academic Unit: Biochemistry (NJMS); Pediatrics - Medical Genetics (RWJMS)
Language: English
Resource Type: Journal article
Identifiers: 991031665484304646