A de novo truncating mutation in ASXL1 associated with segmental overgrowth

Efthymiou, Stéphanie; Salpietro, Vincenzo; Pironti, Erica; Bonsignore, Maria R.; Ferrazzoli, Valentina; Rosa, Gabriella Di; Houlden, Henry

doi:10.1007/s12041-019-1155-5

Cited by 5 publications

(4 citation statements)

References 11 publications

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“…Furthermore, ASXL1 loss-of-function mutations were also observed by whole-exome sequencing in patients with Bohring–Opitz syndrome 49 . Recently, a de novo truncating mutation in ASXL1 was detected in an individual with abnormalities, including severe hypotonia, developmental delay, a mid-line capillary malformation, and distinctive craniofacial features 50 .…”

Section: Bap1 Complex’s Function In the Developmentmentioning

confidence: 99%

Emerging multifaceted roles of BAP1 complexes in biological processes

Szczepanski

Wang

2021

Cell Death Discov.

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Histone H2AK119 mono-ubiquitination (H2AK119Ub) is a relatively abundant histone modification, mainly catalyzed by the Polycomb Repressive Complex 1 (PRC1) to regulate Polycomb-mediated transcriptional repression of downstream target genes. Consequently, H2AK119Ub can also be dynamically reversed by the BAP1 complex, an evolutionarily conserved multiprotein complex that functions as a general transcriptional activator. In previous studies, it has been reported that the BAP1 complex consists of important biological roles in development, metabolism, and cancer. However, identifying the BAP1 complex’s regulatory mechanisms remains to be elucidated due to its various complex forms and its ability to target non-histone substrates. In this review, we will summarize recent findings that have contributed to the diverse functional role of the BAP1 complex and further discuss the potential in targeting BAP1 for therapeutic use.

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Section: Bap1 Complex’s Function In the Developmentmentioning

confidence: 99%

Emerging multifaceted roles of BAP1 complexes in biological processes

Szczepanski

Wang

2021

Cell Death Discov.

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“…ASXL1 encodes a chromatin-binding protein required for normal determination of segment identity in the developing embryo [27] . The protein is a member of the polycomb group of proteins, which are involved in embryogenesis and carcinogenesis through transcriptional regulation of target genes [28] .…”

Section: Discussionmentioning

confidence: 99%

“…[25,26] ASXL1 encodes a chromatin-binding protein required for normal determination of segment identity in the developing embryo. [27] The protein is a member of the polycomb group of proteins, which are involved in embryogenesis and carcinogenesis through transcriptional regulation of target genes. [28] The ASXL1 protein is thought to disrupt chromatin in localized areas, enhancing the transcription of certain genes while repressing the transcription of others.…”

Section: Discussionmentioning

confidence: 99%

Bohring-Opitz syndrome caused by a novel ASXL1 mutation (c.3762delT) in an IVF baby

et al. 2022

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Rationale: Bohring-Opitz syndrome is a severe congenital disorder associated with a de novo mutation in the additional sex combs-like 1 (ASXL1) gene, and it is characterized by symptoms that include developmental delay and musculoskeletal and neurological features.Patient concerns: The patient was a girl, an in vitro fertilization (IVF) baby, with delayed motor development, drooling, short stature, slow growth, low muscle tone, image diagnosis of hypoplasia of the corpus callosum, delayed tooth eruption, high palatal arch, adduction of the thumb, drooling, not chewing, excessive joint activity, and ligament relaxation.Diagnosis: Whole-exome sequencing analysis detected 1 novel disruptive frameshift mutation in ASXL1 in the proband but wildtype ASXL1 in both parents. Interventions: Approximately 1 year of rehabilitation training, which included exercise therapy, toy imitation operation, cognition of daily objects, daily living skills training, gesture language training, oral muscle training, and hand movement training.Outcomes: After approximately 1 year of training, the patient was 3 years old and able to eat normally without drooling. She was able to grasp objects and pick them up after they fell. She was able to grasp small objects and actively played with toys. In addition, she was able to crawl on the floor (at slow speed, with poor initiative), stand with assistance, and walk with assistance; she was unstable when standing unassisted (standing unassisted for 8 seconds at most during training).Lesson: ASXL1 c.3762delT is a novel mutation that may be caused by IVF. This finding suggests that appropriate gene mutation detection approaches may be necessary for IVF technology.Abbreviations: ARTs = assisted reproductive technologies, ASXL1 = additional sex combs-like 1, BOS = Bohring-Opitz syndrome, IVF = in vitro fertilization.

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“…The search time was from the establishment of the database to June 30, 2021. Twenty documents were retrieved ( 3 , 7 – 13 , 15 – 26 ), including 1 Chinese document and 19 English documents. A total of 40 patients with BOS carried ASXL1 gene variants, and their clinical characteristics are summarized in Table 1 .…”

Section: Literature Reviewmentioning

confidence: 99%

A de novo Variant of ASXL1 Is Associated With an Atypical Phenotype of Bohring-Opitz Syndrome: Case Report and Literature Review

et al. 2021

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Bohring-Opitz syndrome (BOS) is a rare genetic disease first reported by Bohring et al. in 1999. With the recent development of exome sequencing (ES), de novo truncating mutations in the additional sex-combs-like 1 (ASXL1) gene have been causally implicated in BOS. Herein, we describe a 7-month-old girl with intrauterine growth restriction, severe pulmonary infection, seizures, and craniofacial abnormalities (microcephaly, micro/retrognathia, hypertelorism, depressed nasal bridge, low-set ears and hypertrichosis) at birth. At a later stage, the patient developed global developmental delay. We performed ES and identified a de novo heterozygous mutation in ASXL1, namely, c.1210C>T/p.R404*. However, this case did not have trigonocephaly, facial hemangioma, prominent eyes, myopia, BOS posture, or brain abnormalities (enlarged subarachnoid spaces, agenesis of the corpus callosum, moderately enlarged cerebral ventricles, or prominent frontal subarachnoid spaces), which are common characteristics in most patients with BOS-harboring ASXL1 mutations. These new data expand the phenotype of BOS driven by ASXL1 and may assist in more accurately delineating the phenotypes caused by variants of this gene.

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A de novo truncating mutation in ASXL1 associated with segmental overgrowth

Cited by 5 publications

References 11 publications

Emerging multifaceted roles of BAP1 complexes in biological processes

Emerging multifaceted roles of BAP1 complexes in biological processes

Bohring-Opitz syndrome caused by a novel ASXL1 mutation (c.3762delT) in an IVF baby

A de novo Variant of ASXL1 Is Associated With an Atypical Phenotype of Bohring-Opitz Syndrome: Case Report and Literature Review

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