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. 2021 Apr 14;12(3):254-257.
doi: 10.1055/s-0041-1728650. eCollection 2023 Sep.

A Novel Pathogenic Variant in the MN1 Gene in a Patient Presenting with Rhombencephalosynapsis and Craniofacial Anomalies, Expanding MN1 C-terminal Truncation Syndrome

Carmen Palma Milla  1 , Pérez Mohand Patricia  2 , José M Lezana  1 , Jaime Cruz  2 , Juan F Quesada  1 , Sara Vila  3 , Isabel Álvarez-Mora  1 , Ana Arteche-López  1 , Irene Gómez-Manjón  1 , M Teresa Sánchez  1 , Maria José Gómez-Rodríguez  1 , Jaime Sánchez  2 , Marta Moreno-García  1
Affiliations

A Novel Pathogenic Variant in the MN1 Gene in a Patient Presenting with Rhombencephalosynapsis and Craniofacial Anomalies, Expanding MN1 C-terminal Truncation Syndrome

Carmen Palma Milla et al. J Pediatr Genet. .

Abstract

Meningioma-1 is a transcription activator that regulates mammalian palate development and is required for appropriate osteoblast proliferation, motility, differentiation, and function. Microdeletions involving the MN1 gene have been linked to syndromes including craniofacial anomalies, such as Toriello-Carey syndrome. Recently, truncating variants in the C-terminal portion of the MN1 transcriptional factor have been linked to a characteristic and distinct phenotype presenting with craniofacial anomalies and partial rhombencephalosynapsis, a rare brain malformation characterized by midline fusion of the cerebellar hemispheres with partial or complete loss of the cerebellar vermis. It has been called MN1 C-terminal truncation (MCTT) syndrome or CEBALID (Craniofacial defects, dysmorphic Ears, Brain Abnormalities, Language delay, and Intellectual Disability) and suggested to be caused by dominantly acting truncated protein MN1 instead of haploinsufficiency. As a proto-oncogene, MN1 is also involved in familial meningioma. In this study, we present a novel case of MCTT syndrome in a female patient presenting with craniofacial anomalies and rhombencephalosynapsis, harboring a de novo pathogenic variant in the MN1 gene: c.3686_3698del, p.(Met1229Argfs*87).

Keywords: MN1; MN1 C-terminal truncation (MCTT) syndrome and craniofacial anomalies; rhombencephalosynapsis.

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Conflict of interest statement

Conflict of Interest None declared.

Figures

Fig. 1
Fig. 1
( A, B ) Facial photographs of affected patient at age 2 years.
Fig. 2
Fig. 2
MRI brain findings in the patient. ( A ) Midline (sagittal view, T1 sequence): callosum corpus hypoplasia and brain atrophy. ( B ) Insula (axial view, T1 sequence): brain atrophy and ventriculomegaly. ( C, D ) Brainstem and posterior fossa ( C : axial view, T1 sequence; D : coronal view, T1 sequence): superior vermis hypoplasia and partial fusion of the cerebellar hemispheres consistent with rhombencephalosynapsis.
Fig. 3
Fig. 3
MN1 variants identified in patients with MCCT syndrome. In red is indicated the novel variant p.(Met1229Argfs*87).
See this image and copyright information in PMC

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