학술논문
Genetic and Phenotypic Analysis of Patients with Mucopolysaccharidosis type IIIB Co-morbid with Autism Spectrum Disorder.
Document Type
Article
Author
Ercan-Şençiçek, A. Gülhan; Barak, Tanyeri; Rai, Devendra K.; Kaymakçalan, Hande; Kaya, İlyas; Erbilgin, Seda; Uytun, Merve Çıkılı; Öztop, Didem; Gümüş, Hakan; Per, Hüseyin; Ceylaner, Serdar; Aromolaran, Kelly; Bozkurt, İçten; Mishra-Gorur, Ketu; Kontaridis, Maria I.; Bilgüvar, Kaya; Kılınçaslan, Ayşe; Çağlayan, Ahmet Okay; Erson-Omay, E. Zeynep; Günel, Murat
Source
Subject
*RECESSIVE genes
*AUTISM spectrum disorders
*CELLULAR control mechanisms
*GLYCOGEN storage disease type II
*PHENOTYPES
*MUCOPOLYSACCHARIDOSIS
*COMORBIDITY
*
*
*
*
*
*
Language
ISSN
1300-056X
Abstract
Mucopolysaccharidosis type IIIB (MPS IIIB) is an autosomal recessive lysosomal disorder caused by mutations in the a-N-acetylglucosaminidase (NAGLU) gene. Our WES and standard Sanger sequencing effort on 220 consanguineous families, in children diagnosed with ASD, identified two recurrent damaging biallelic p.D312N and p.R234G variants in the NAGLU gene in seven cases of four families. All affected individuals' enzymatic assay in leukocytes clearly showed that a-N-acetylglucosaminidase was completely inactive. Structure modeling of these mutations suggested that each mutation affects the stability of the enzyme and results in a loss of activity. knn-DREMI analysis of scRNAseq data of the developing human brain identified that several genes implicated in neurodegenerative disorders are positively regulated with NAGLU expression. Among these genes, mutations in CLN5 and ZBTB20 were linked to neurodevelopmental disorders including autism. Our findings suggest that molecular and cellular mechanisms controlled by the genes positively regulated with NAGLU expression have promise to develop the potential treatment for neurodevelopment and neurodegeneration in patients with MPS IIIB and autism. [ABSTRACT FROM AUTHOR]