A novel case of two siblings harbouring homozygous variant in the NEUROG1 gene with autism as an additional phenotype: a case report

BMC Neurology

Case Report

Darshan Patel¹  Jayesh Sheth²  Jhanvi Shah²  Frenny Sheth²  Harsh Sheth²  Deepika Jain³  Ketan Patel⁴ 

[1] Charotar Institute of Paramedical Sciences, Charotar University of Science and Technology, Changa, Gujarat, India;FRIGE’s Institute of Human Genetics, FRIGE House, Jodhpur Gam Road, 380015, Satellite, Ahmedabad, India;Shishu Child Development and Early Intervention Centre, Ahmedabad, India;Speciality Homeopathy Clinic, Ahmedabad, India;

关键词: Autism spectrum disorder (ASD);    Basic helix-loop-helix (bHLH);    Congenital cranial dysinnervation disorders (CCDD);    Cranial nerves;    Loss of function;    NEUROG1;    Neurogenin;   

DOI  :  10.1186/s12883-023-03065-1

 received in 2022-09-09, accepted in 2023-01-11,  发布年份 2023

来源: Springer

【 摘 要 】

IntroductionNEUROG1 gene is yet to be associated with a set of human phenotypes in the OMIM database. Three cases have previously been diagnosed with cranial dysinnervation due to biallelic variants in the NEUROG1 gene. This is the fourth and a novel report of a sibling pair harboring a homozygous variant in the NEUROG1 gene with autism as an additional phenotype. A brief review of the literature in conjunction with a genotype–phenotype correlation has been described. A potential hypothesis for the presence of the autistic phenotype in the present case has also been elucidated.Case presentationA female aged 6 years and 9 months born to endogamous and phenotypically healthy parents was diagnosed with global developmental delay, autism spectrum disorder, hearing loss, corneal opacity and no eye blinking. Her MRI of the brain revealed mild peritrigonal white matter hyperintensity, and MRI and CT scan of the temporal bones showed abnormal cranial nerves. The proband’s younger sister, aged 4-years, was similarly affected. Whole exome sequencing was performed in the proband, which revealed a novel homozygous, likely pathogenic, truncating frameshift variant, c.228_231dup (p.Thr78ProfsTer122) in exon 1 of the NEUROG1 gene (ENST00000314744.4). Segregation analysis by Sanger sequencing showed the proband and her younger sister to be homozygotes and their parents to be heterozygous carriers.ConclusionThis is the fourth report across the globe with a variant identified in the NEUROG1 gene to be associated with cranial dysinnervation phenotype. An additional phenotype of autism in two female siblings was a novel observation. We provide a hypothetical framework which could explain the pleiotropic effect of a dysfunctional NEUROG1 protein leading to autism and posit it as a candidate for diagnosis of autism spectrum disorder with congenital cranial dysinnervation disorder.

【 授权许可】

CC BY   
© The Author(s) 2023

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Fig. 27

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