X‐linked mental retardation‐hypotonic facies syndrome: Exome sequencing identifies novel clinical characteristics associated with c.5182G&gt;C mutation in the <i>ATRX</i> gene

Shakarami, Fatemeh; Jahani, Mehdi; Nouri, Zahra; Tabatabaiefar, Mohammad Amin

doi:10.1002/mgg3.2034

Cited by 3 publications

(1 citation statement)

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“…Next-generation sequencing (NGS) as a high-throughput sequencing method provides the opportunity to uncover known and novel disease-associated genes in genetically heterogeneous disorders. [ 5 ] Here we report the successful application of whole-exome sequencing (WES) to identify a rare pathogenic nonsense variant in large inbred kindred with several individuals affected by cutaneous photosensitivity from the northeast of Iran.…”

Section: Introductionmentioning

confidence: 99%

A Homozygous Nonsense Variant in UVSSA Causes UV-sensitive Syndrome from Very Large Kindred: The First Report from Iran

Ahmadi Shadmehri,

Akbarian,

Rahimi

et al. 2023

Advanced Biomedical Research

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Background: Recessive disruptive mutations in nucleotide excision repair genes are responsible for a wide range of cutaneous photosensitivity and, in some cases, are associated with multi-system involvement. The heterogeneous nature of these conditions makes next-generation sequencing the method of choice to detect disease-causing variants. Materials and Methods: A patient from a large multiplex inbred Iranian kindred with several individuals suffering from skin sun-sensitive manifestations underwent complete clinical and molecular evaluations. Whole exome sequencing (WES) was performed on the genomic sample of the proband, followed by bioinformatics analysis. Subsequently, co-segregation of the candidate variant with the condition was performed by Sanger sequencing. Results: A rare homozygous nonsense variant, c.1040G>A (p. Trp347*), was identified in the UVSSA gene, resulting in UV-sensitive syndrome (UVSS) complementation group A. The global minor allele frequency of the variant is < 0.001 in population databases. Tryptophan 347 residue is conserved among mammalians and vertebrates, and the null variant is believed to lead to a truncated protein with cellular mislocalization. Conclusions: Here, we report the first genetic diagnosis of UVSS-A in Iran via the successful application of Next-generation sequencing, which expands our understanding of the molecular pathogenesis of this condition.

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Section: Introductionmentioning

confidence: 99%

A Homozygous Nonsense Variant in UVSSA Causes UV-sensitive Syndrome from Very Large Kindred: The First Report from Iran

Ahmadi Shadmehri,

Akbarian,

Rahimi

et al. 2023

Advanced Biomedical Research

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X‐linked mental retardation‐hypotonic facies syndrome: Exome sequencing identifies novel clinical characteristics associated with c.5182G>C mutation in the ATRX gene

Shakarami

Jahani

Nouri

et al. 2022

Molec Gen & Gen Med

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Identification of a Novel Frameshift variant of the ATRX gene: a Case Report and Review of the genotype–phenotype relationship

Wang,

Ma,

Chen

et al. 2024

BMC Pediatr

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Background X-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 review A 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. Conclusion We 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. Supplementary Information The online version contains supplementary material available at 10.1186/s12887-024-05088-0.

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X‐linked mental retardation‐hypotonic facies syndrome: Exome sequencing identifies novel clinical characteristics associated with c.5182G>C mutation in the ATRX gene

Cited by 3 publications

References 44 publications

A Homozygous Nonsense Variant in UVSSA Causes UV-sensitive Syndrome from Very Large Kindred: The First Report from Iran

A Homozygous Nonsense Variant in UVSSA Causes UV-sensitive Syndrome from Very Large Kindred: The First Report from Iran

X‐linked mental retardation‐hypotonic facies syndrome: Exome sequencing identifies novel clinical characteristics associated with c.5182G>C mutation in the ATRX gene

Identification of a Novel Frameshift variant of the ATRX gene: a Case Report and Review of the genotype–phenotype relationship

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