Bainbridge-ropers syndrome caused by loss-of-function variants in ASXL3: Clinical abnormalities, medical imaging features, and gene variation in infancy of case report

Yang, Linfeng; Guo, Bin; Zhu, Weiwei; Wang, Lei; Han, Bing; Che, Yena; Guo, Lingfei

doi:10.1186/s12887-020-02027-7

Cited by 11 publications

(20 citation statements)

References 23 publications

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“…The most common facial dysmorphism in the literature is high-arched palate, followed by arched eyebrows, anteverted nares, downslanting palpebral fissures, strabismus, and prominent forehead ( ). Additionally, hand anomalies such as ulnar deviation of hands at rest (5/7, 71.4%) and hypertonic extremities (5/6, 83.3%) have been frequently reported in Chinese BRPS patients and were also seen in our patient[ 6 - 9 ]. The incidence of these hand anomalies might be underestimated.…”

Section: Discussionsupporting

confidence: 51%

“…The only one exception was a splice site mutation (located in intron 11) detected in two unrelated patients reported by Myers et al [ 11 ] and Hori et al [ 18 ], respectively. In addition to the recurrent splice site mutation, three other mutations were detected more than once in unrelated families, including c.3106C>T (p.R1036*)[ 7 , 8 , 11 , 13 , 17 ], c.3494_3495del (p.C1165*)[ 6 , 13 ], and c.4330C>T (p.R1444*)[ 2 , 3 ]. The mutation c.3106C>T (p.R1036*) was identified in five separate families in the literature, suggesting it is a likely mutational hotspot.…”

Section: Discussionmentioning

confidence: 99%

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Novel mutation in the ASXL3 gene in a Chinese boy with microcephaly and speech impairment: A case report

Li¹,

Huang²,

Lü³

et al. 2020

WJCC

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BACKGROUND Bainbridge-Ropers syndrome (BRPS) is a severe disorder characterized by failure to thrive, facial dysmorphism, and severe developmental delay. BRPS is caused by a heterozygous loss-of-function mutation in the ASXL3 gene. Due to limited knowledge of the disease and lack of specific features, clinical diagnosis of this syndrome is challenging. With the use of trio-based whole exome sequencing, we identified a novel ASXL3 mutation in a Chinese boy with BRPS and performed a literature review. CASE SUMMARY A 3-year-old Chinese boy was referred to our hospital due to progressive postnatal microcephaly and intellectual disability with severe speech impairment for 2 years. His other remarkable clinical features were shown as follows: Facial dysmorphism, feeding difficulties, poor growth, motor delay, and abnormal behavior. For the proband, regular laboratory tests, blood tandem mass spectrometry, urine gas chromatographic mass spectrometry, karyotype, hearing screening, and brain magnetic resonance imaging were performed, with negative results. Therefore, for the proband and his unaffected parents, trio-based whole exome sequencing and subsequent validation by Sanger sequencing were performed. A novel nonsense variant in exon 11 of the ASXL3 gene (c.1795G>T; p.E599*) was detected, present in the patient but absent from his parents. Taking into account the concordant phenotypic features of our patient with reported BRPS patients and the detected truncated variant located in the known mutational cluster region, we confirmed a diagnosis of BRPS for this proband. The rehabilitation treatment seemed to have a mild effect. CONCLUSION In this case, a novel nonsense mutation (c.1795G>T, p.E599*) in ASXL3 gene was identified in a Chinese boy with BRPS. This finding not only contributed to better genetic counseling and prenatal diagnosis for this family but also expanded the pathogenic mutation spectrum of ASXL3 gene and provided key information for clinical diagnosis of BRPS.

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Novel mutation in the ASXL3 gene in a Chinese boy with microcephaly and speech impairment: A case report

Li¹,

Huang²,

Lü³

et al. 2020

WJCC

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“…BRPS was rst described in 2013, in four patients with ASXL3 de novo mutations. To date, 54 patients with a wide age range from 4 months to 47 years were reported [1,2,5,[11][12][13][14][15][16][17][18][19][20][22][23][24][25][26][27][28][29][30]. Mutation spectrum of ASXL3 and the number of patients were listed in Table 1.…”

Section: Discussionmentioning

confidence: 99%

“…To our knowledge, 54 cases with ASXL3 LOF variants and one splicing mutation have been reported including ten Chinese patients [12][13][14][15][16][17][18]. The studies demonstrate clinical heterogeneity exists in the affected subjects and the correlation between the position of variants and the severity of the phenotype is uncertain [5,17,19].…”

Section: Introductionmentioning

confidence: 99%

De Novo Nonsense Variant in ASXL3 in a Chinese Girl Causing Bainbridge–Ropers Syndrome: A Case Report and Review of Literature

Wang

Zhang

Jiang

et al. 2021

Preprint

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Background: Bainbridge-Ropers syndrome (BRPS, OMIM #615485) was first identified in 2013 by Bainbridge et al. and is a neurodevelopment disorder characterized by failure to thrive, facial dysmorphism, and severe developmental delay. BRPS is caused by heterozygous loss-of function (LOF) variants in the additional sex combs-like 3 (ASXL3) gene which are mostly located in two mutational cluster regions (MCR). Due to the limited specific recognizable features and overlapping symptoms with Bohring–Opitz syndrome, clinical diagnosis of BRPS is challenging. Case presentation: In this study, a 2-year-8-month-old Chinese girl was referred for genetic evaluation of severe developmental delay. Reduced fetal movement was found during antenatal period and bilateral varus deformity of feet was observed at birth. Whole exome sequencing and Sanger sequencing were used to detect and confirm the variant. A novel nonsense variant c.1063G>T (p.E355X) in the ASXL3 gene (NM_030632.3) was identified in the proband and the clinical symptoms were compatible with BRPS. The parents were physical and genetic normal and prenatal diagnosis was requested for her pregnant mother with a negative Sanger sequencing result. Conclusion: The study revealed a de novo LOF variant in the ASXL3 gene and expanded the mutation spectrum for this clinical condition. By performing a literature review, we analyzed the clinical phenotype with limited fetal features and summarized genetic results of all BPRSs reported so far. More cases study may help to elucidate the function of ASXL3 gene that may be critical to understand the genetic etiology of this syndrome and assist in accurate genetic counselling, informed decision making and prenatal diagnosis.

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“…ASXL3, the pathogenic gene of rare BRPS, is a member of the ASXL gene family, located at 18q12.1, with a length of 6.8 kb, containing 12 exons and encoding the multicomb protein [1] .…”

Section: Discussionmentioning

confidence: 99%

Bainbridge-Roper syndrome: A rare case of developmental delay

Vatkar¹,

Dolas²,

Kanmani³

et al. 2021

Int. J. Paediatrics Geriatrics

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ASXL3 mutations were first identified in 2013 by Bainbridge et al. as a cause of syndromic intellectual disability in four children with similar phenotypes using whole-exome sequencing. The clinical featurespostulated by Bainbridge et al. were developmental delay, severe feeding difficulties, failure to thrive and neurological abnormalities. To date, a total of nine individuals with BRPS have been published in the literature in four reports (Bainbridge et al., Dinwiddie et al, Srivastava et al. and Hori et al.). In this report, we describe an uncertain variant present in Exon 11 of ASXL3(+) heterozygous zygosity in a female child with clinical features: truncal muscular hypotonia with significant motor delay, profound speech impairment, intellectual disability and a characteristic dysmorphic facies phenotype (open mouth, full lips, depressed nasal bridge, metopic prominence, microcephaly (45.5.cm), with camptodactyly and dysplastic fingers). Hence, we are reporting a rare case of developmental delay.

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Bainbridge-ropers syndrome caused by loss-of-function variants in ASXL3: Clinical abnormalities, medical imaging features, and gene variation in infancy of case report

Cited by 11 publications

References 23 publications

Novel mutation in the ASXL3 gene in a Chinese boy with microcephaly and speech impairment: A case report

Novel mutation in the ASXL3 gene in a Chinese boy with microcephaly and speech impairment: A case report

De Novo Nonsense Variant in ASXL3 in a Chinese Girl Causing Bainbridge–Ropers Syndrome: A Case Report and Review of Literature

Bainbridge-Roper syndrome: A rare case of developmental delay

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