Atypical phenotype? The answer’s in the genotype: AGS caused by a novel <i>RNASEH2C</i> variant combined with XLA caused by a BTK deficiency

Boulanger, C.; Chatzis, Olga; Nolf, Delphine; Brichard, Bénédicte; Lauwerys, Bernard; Nassogne, Marie‐Cécile; Limaye, Nisha

doi:10.1093/rheumatology/keab051

Cited by 1 publication

(6 citation statements)

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“…The three novel variants identified in our affected patients further expand the RNASEH2C mutation spectrum. To date, a total of 22 variants, including the three novel variants in our study, have been identified 2,9,11,15,16 . RNASEH2C null variants (frameshift and splicing) and missense variants account for 9.1% and 90.9%, respectively, and are located in exons 1–3 and intron 1 (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

“…Currently, approximately 50 individuals with AGS3 and 19 RNASEH2C variants have been reported. [1][2][3][9][10][11][12][13][14][15][16] Unfortunately, detailed clinical information for most cases is not available, hindering the clinical diagnosis and management of RNA-SEH2C-related AGS3.…”

Section: Discussionmentioning

confidence: 99%

“…To date, a total of 22 variants, including the three novel variants in our study, have been identified. 2,9,11,15,16 RNASEH2C null variants (frameshift and splicing) and missense variants account for 9.1% and 90.9%, respectively, and are located in exons 1-3 and intron 1 (Figure 2). No biallelic null variants have been detected in affected patients, suggesting that biallelic null variants could cause clinical outcomes that are too severe to be compatible with live birth.…”

Section: Discussionmentioning

confidence: 99%

“…Biallelic pathogenic variants in RNASEH2C cause AGS3, a rare autosomal recessive encephalopathy. Currently, approximately 50 individuals with AGS3 and 19 RNASEH2C variants have been reported 1–3,9–16 . Unfortunately, detailed clinical information for most cases is not available, hindering the clinical diagnosis and management of RNASEH2C ‐related AGS3.…”

Section: Discussionmentioning

confidence: 99%

“…Aicardi‐Goutières syndrome 3 (AGS3, MIM #610329), caused by biallelic pathogenic variants in RNASEH2C , is rarely reported. Currently, approximately 50 individuals with molecularly confirmed AGS3 have been reported worldwide, and 19 variants in RNASEH2C have been identified 9–16 . Most affected patients are from the Caucasian population; only three are Chinese patients without detailed clinical phenotypes 15 .…”

Section: Introductionmentioning

confidence: 99%

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RNASEH2C c.194G>A is a Chinese‐specific founder mutation in three unrelated patients with Aicardi‐Goutières syndrome 3

Wang

Zhou

et al. 2023

Clinical Genetics

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Biallelic pathogenic variants in RNASEH2C cause Aicardi‐Goutières syndrome 3 (AGS3, MIM #610329), a rare early‐onset encephalopathy characterized by intermittent unexplained fever, chilblains, irritability, progressive microcephaly, dystonia, spasticity, severe psychomotor retardation and abnormal brain imaging. Currently, approximately 50 individuals with AGS3 and 19 variants in RNASEH2C have been revealed. Here, we reported the novel clinical manifestations and genotypic information of three unrelated Chinese patients with AGS3 caused by pathogenic variants in RNASEH2C. In addition to three novel missense variants (c.101G>A, p.Cys34Tyr; c.401T>A, p.Leu134Gln and c.434G>T, p.Arg145Leu), one missense variant (c.194G>A, p.Gly65Asp) reoccurred in all patients but was completely absent in South Asian and other ethnicities. Our study expanded the variant spectrum of RNASEH2C and identified RNASEH2C c.194G>A as a Chinese‐specific founder mutation. The novel phenotypes, including mouth ulcers, hip dysplasia, retarded dentition and hypogonadism, observed in our patients greatly enriched the clinical characteristics of AGS3.

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Section: Discussionmentioning

confidence: 99%