Novel truncating mutations in ASXL1 identified in two boys with Bohring-Opitz syndrome

Zhao, Jianbo; Hou, Yanqi; Fang, Fang; Ding, Changhong; Yang, Xinying; Li, Jiuwei; Cui, Di; Cao, Zhenhua; Zhang, Hao

doi:10.1016/j.ejmg.2021.104155

Cited by 3 publications

(3 citation statements)

References 20 publications

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“…Furthermore, exon sequencing of the whole gene showed that the ASXL1 gene had a c.3762delT frameshift mutation. However, the head sizes of our proband were normal, which is contrary to the microcephaly reported in every other case with ASXL1 disease-causing variants [25,26] …”

Section: Discussioncontrasting

confidence: 99%

“…However, the head sizes of our proband were normal, which is contrary to the microcephaly reported in every other case with ASXL1 disease-causing variants. [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.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussioncontrasting

confidence: 99%

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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“…Cases of children with ASXL1 variants have been reported primarily in Western countries, with only 7 cases reported in Asian countries [3 cases in China ( 7 , 8 ), 1 in India ( 9 ), 1 in Japan ( 10 ), 1 in Turkey ( 11 ) and 1 in Korea ( 12 )]. In this study, a Chinese child with BOS was found to carry an ASXL1 gene variant.…”

Section: Introductionmentioning

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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Prenatal exome sequencing, a powerful tool for improving the description of prenatal features associated with genetic disorders

Thauvin‐Robinet,

Garde,

Delanne

et al. 2024

Prenatal Diagnosis

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ObjectivePrenatal exome sequencing (pES) is now commonly used in clinical practice. It can be used to identifiy an additional diagnosis in around 30% of fetuses with structural defects and normal chromosomal microarray analysis (CMA). However, interpretation remains challenging due to the limited prenatal data for genetic disorders.MethodWe conducted an ancillary study including fetuses with pathogenic/likely pathogenic variants identified by trio‐pES from the “AnDDI‐Prenatome” study. The prenatal phenotype of each patient was categorized as typical, uncommon, or unreported based on the comparison of the prenatal findings with documented findings in the literature and public phenotype‐genotype databases (ClinVar, HGMD, OMIM, and Decipher).ResultsPrenatal phenotypes were typical for 38/56 fetuses (67.9%). For the others, genotype‐phenotype associations were challenging due to uncommon prenatal features (absence of recurrent hallmark, rare, or unreported). We report the first prenatal features associated with LINS1 and PGM1 variants. In addition, a double diagnosis was identified in three fetuses.ConclusionStandardizing the description of prenatal features, implementing longitudinal prenatal follow‐up, and large‐scale collection of prenatal features are essential steps to improving pES data interpretation.

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Novel truncating mutations in ASXL1 identified in two boys with Bohring-Opitz syndrome

Cited by 3 publications

References 20 publications

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

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

Prenatal exome sequencing, a powerful tool for improving the description of prenatal features associated with genetic disorders

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