Dataset Information

MN1 Neurodevelopmental Disease-Atypical Phenotype Due to a Novel Frameshift Variant in the MN1 Gene.

ABSTRACT: Background: MN1 C-terminal truncation (MCTT) syndrome is caused by variants in the C-terminal region of MN1, which were first described in 2020. The clinical features of MCTT syndrome includes severe neurodevelopmental and brain abnormalities. We reported on a patient who carried the MN1 variant in the C-terminal region with mild developmental delay and normal brain magnetic resonance image (MRI). Methods: Detailed clinical information was collected in the pedigree. Whole-exome sequencing (WES) accompanied with Sanger sequencing validation were performed. A functional study based on HEK239T cells was performed. Results: A de novo heterozygous c.3734delT: p.L1245fs variant was detected. HEK239T cells transinfected with the de novo variant showed decreased proliferation, enhanced apoptotic rate, and MN1 nuclear aggregation. Conclusion: Our study expended the clinical and genetic spectrum of MCTT which contributes to the genetic counseling of the MN1 gene.

SUBMITTER: Tian Q

PROVIDER: S-EPMC8716923 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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MN1 Neurodevelopmental Disease-Atypical Phenotype Due to a Novel Frameshift Variant in the MN1 Gene.

Tian Qi Q Shu Li L Zhang Pu P Zeng Ting T Cao Yang Y Xi Hui H Peng Ying Y Wang Yaqin Y Mao Xiao X Wang Hua H

Frontiers in molecular neuroscience 20211216

Background: MN1 C-terminal truncation (MCTT) syndrome is caused by variants in the C-terminal region of MN1, which were first described in 2020. The clinical features of MCTT syndrome includes severe neurodevelopmental and brain abnormalities. We reported on a patient who carried the MN1 variant in the C-terminal region with mild developmental delay and normal brain magnetic resonance image (MRI). Methods: Detailed clinical information was collected in the pedi ...[more]

PMID: 34975401

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Project description:BackgroundX-linked intellectual disability-hypotonic facies syndrome-1 (MRXHF1) and Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome are caused by pathogenic variant in the ATRX gene, a member of the switch/sucrose non-fermentable (SWI-SNF) protein family that exhibits chromatin remodeling activity. These syndromes show a wide spectrum of clinical manifestations, such as distinctive dysmorphic features, mild-to-profound intellectual disability, motor development delay, seizures, urogenital abnormalities, and gastrointestinal disorders.Case presentation and literature reviewA 3-year-old boy from a Chinese non-consanguineous family was diagnosed with MRXHF1 by whole-exome sequencing. Comprehensive family history information was obtained. The Medline database was searched until 1st Aug 2023 for articles related to ATRX pathogenic variant. Data on gene/protein mutations and clinical symptoms were extracted. The proband showed intellectual disability, motor development delay, typical facial abnormalities, urogenital defect, behavior problems, and optical nerve dysplasia. A novel frameshift mutation c.399_400dup, (p.Leu134Cysfs*2) in the ATRX gene was the primary cause, which occurs right before the ATRXDNMT3-DNMT3L (ADD) domain of ATRX protein. Missense mutation is the most common variation type. The ADD and helicase-like domains are the most frequently affected domains. Epilepsy, congenital heart disease, urogenital defect, acoustic defect, and optical defect are more prevalent in patients with frameshift mutations compared to those with missense mutations. There are more urogenital defects with C-terminal frameshift mutations than with N-terminal frameshift mutations.ConclusionWe described a novel frameshift mutation in the ATRX gene in a patient with MRXHF1 syndrome and summarized the genotype-phenotype relationship of ATRX pathogenic variant by variation type and affected protein domain. The regulatory mechanism underlying ATRX variant requires comprehensive analysis in future studies.

Dataset Information

MN1 Neurodevelopmental Disease-Atypical Phenotype Due to a Novel Frameshift Variant in the MN1 Gene.

Publications

<i>MN1</i> Neurodevelopmental Disease-Atypical Phenotype Due to a Novel Frameshift Variant in the <i>MN1</i> Gene.

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