Case Report : a Novel ASXL3 Gene Variant in a Sudanese Boy

Overview

Journal BMC Pediatr

Publisher Biomed Central

Specialty Pediatrics

Date 2021 Dec 10

PMID 34886823

Authors

Ke Wu

Yan Cong

Affiliations

Soon will be listed here.

Abstract

Background: Bainbridge-Ropers syndrome (BRPS) [OMIM#615485] is a neurodevelopmental disorder, characterized by delayed psychomotor development with generalized hypotonia, moderate to severe intellectual disability, poor or absent speech, feeding difficulties, growth failure, dysmorphic craniofacial features and minor skeletal features. The aim of this study was to investigate the genetic etiology of a Sudanese boy with severe developmental delay, intellectual disability, and craniofacial phenotype using trio-based whole-exome sequencing. To our knowledge, no patients with ASXL3 gene variant c.3043C>T have been reported detailedly in literature.

Case Presentation: The patient (male, 3 years 6 months) was the first born of a healthy non-consanguineous couple originating from Sudan, treated for "psychomotor retardation" for more than 8 months in Yiwu. The patient exhibited severely delayed milestones in physiological and intellectual developmental stages, language impairment, poor eye-contact, lack of subtle motions of fingers, fear of claustrophobic space, hypotonia, clinodactyly, autistic features. Peripheral blood samples were collected from the patient and his parents. Trio-based whole-exome sequencing(Trio-WES) identified a de novo heterozygous ASXL3 gene variant c.3043C>T;p.Q1015X. Sanger sequencing verified variants of this family.

Conclusion: Trio-WES analysis identified a de novo nonsense variant (c.3043C>T) of ASXL3 gene in a Sudanese boy. To our knowledge, the patient with this variant has not been reported previously in literature. This study presents a new case for ASXL3 gene variants, which expanded the mutational and phenotypic spectrum.

References

Fu F, Li R, Lei T, Wang D, Yang X, Han J . Compound heterozygous mutation of the ASXL3 gene causes autosomal recessive congenital heart disease. Hum Genet. 2020; 140(2):333-348. DOI: 10.1007/s00439-020-02200-z. View

Katoh M, Katoh M . Identification and characterization of ASXL3 gene in silico. Int J Oncol. 2004; 24(6):1617-22. View

Tso W, Wong V, Xia X, Faragher B, Li M, Xu X . The Griffiths Development Scales-Chinese (GDS-C): A cross-cultural comparison of developmental trajectories between Chinese and British children. Child Care Health Dev. 2018; 44(3):378-383. DOI: 10.1111/cch.12548. View

Nah Y, Young R, Brewer N . Using the Autism Detection in Early Childhood (ADEC) and Childhood Autism Rating Scales (CARS) to predict long term outcomes in children with autism spectrum disorders. J Autism Dev Disord. 2014; 44(9):2301-10. DOI: 10.1007/s10803-014-2102-1. View

Koboldt D, Mosher T, Kelly B, Sites E, Bartholomew D, Hickey S . A de novo nonsense mutation in shared by siblings with Bainbridge-Ropers syndrome. Cold Spring Harb Mol Case Stud. 2018; 4(3). PMC: 5983172. DOI: 10.1101/mcs.a002410. View

Bao Nan , Bo Y, Yun-Hai S, Cheng C, Xiong-Zheng M . Extensive cranioplasty for sagittal synostosis in young children by preserving cranial bone flaps adhered to the dura mater. J Craniofac Surg. 2015; 26(2):368-72. DOI: 10.1097/SCS.0000000000001476. View

Balasubramanian M, Willoughby J, Fry A, Weber A, Firth H, Deshpande C . Delineating the phenotypic spectrum of Bainbridge-Ropers syndrome: 12 new patients with , heterozygous, loss-of-function mutations in and review of published literature. J Med Genet. 2017; 54(8):537-543. DOI: 10.1136/jmedgenet-2016-104360. View

Bainbridge M, Hu H, Muzny D, Musante L, Lupski J, Graham B . De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome. Genome Med. 2013; 5(2):11. PMC: 3707024. DOI: 10.1186/gm415. View

Giri D, Rigden D, Didi M, Peak M, McNamara P, Senniappan S . Novel compound heterozygous mutation causing Bainbridge-ropers like syndrome and primary IGF1 deficiency. Int J Pediatr Endocrinol. 2017; 2017:8. PMC: 5544984. DOI: 10.1186/s13633-017-0047-9. View

10.

Kuechler A, Czeschik J, Graf E, Grasshoff U, Huffmeier U, Busa T . Bainbridge-Ropers syndrome caused by loss-of-function variants in ASXL3: a recognizable condition. Eur J Hum Genet. 2016; 25(2):183-191. PMC: 5255962. DOI: 10.1038/ejhg.2016.165. View

11.

Yu K, Luk H, Fung J, Chung B, Lo I . Further expanding the clinical phenotype in Bainbridge-Ropers syndrome and dissecting genotype-phenotype correlation in the ASXL3 mutational cluster regions. Eur J Med Genet. 2020; 64(1):104107. DOI: 10.1016/j.ejmg.2020.104107. View

12.

Fu C, Luo S, Zhang Y, Fan X, DGama A, Zhang X . Chromosomal microarray and whole exome sequencing identify genetic causes of congenital hypothyroidism with extra-thyroidal congenital malformations. Clin Chim Acta. 2018; 489:103-108. DOI: 10.1016/j.cca.2018.11.035. View

13.

Stone W, Coonrod E, Turner L, Pozdol S . Psychometric properties of the STAT for early autism screening. J Autism Dev Disord. 2005; 34(6):691-701. DOI: 10.1007/s10803-004-5289-8. View

14.

Myers K, White S, Mohammed S, Metcalfe K, Fry A, Wraige E . Childhood-onset generalized epilepsy in Bainbridge-Ropers syndrome. Epilepsy Res. 2018; 140:166-170. DOI: 10.1016/j.eplepsyres.2018.01.014. View

15.

Bacrot S, Mechler C, Talhi N, Martin-Coignard D, Roth P, Michot C . Whole exome sequencing diagnoses the first fetal case of Bainbridge-Ropers syndrome presenting as pontocerebellar hypoplasia type 1. Birth Defects Res. 2018; 110(6):538-542. DOI: 10.1002/bdr2.1191. View