Comparison of Genetic Variants and Manifestations of OTUD6B-Related Disorder: The First Mexican Case

Abstract

The intellectual disability syndrome characterized by seizures and dysmorphic features was initially described in 2017 and was associated with genetic variants in the OTUD6B gene, identified by exome sequencing (ES) in a large cohort. This multisystem disorder primarily affects the central nervous system, the gastrointestinal, and the skeletal systems. In this article, we describe the first Mexican patient diagnosed by ES. The homozygous c.433C>T (p.Arg145*) variant of the OTUD6B gene confirmed this intellectual disability syndrome. In addition to seizures and other more frequently reported manifestations of this condition, this is the third patient with associated hypothyroidism and hypogammaglobulinemia, underscoring the value of screening for these conditions in other patients. The current challenge with this patient is to ensure medical management of his seizures and provide him with a better quality of life. The possibilities of additional therapeutic approaches may increase by understanding the physiopathology of the involved pathways.

Compound Heterozygote of Point Mutation and Chromosomal Microdeletion Involving OTUD6B Coinciding with ZMIZ1 Variant in Syndromic Intellectual Disability

“…The current study shows that dysmorphic features, including periorbital edema and hanging cheek resembling Williams syndrome, can be part of the facial gestalt of OTUD6B-related ID. This extends the list of overlapping syndromes of this rare disorder, in addition to Kabuki syndrome and Rubinstein-Taybi syndrome [7,10]. These findings support the notion that different ethnic backgrounds could affect the overall craniofacial appearance of individuals, both normal and those affected with teratogenic/genetic disorders [20,21].…”

“…Nine mutations of OTUD6B have been reported in 12 families, all of them were from Hispanic origin or were from Mediterranean countries [5][6][7][8][9][10]. Our patient represents the first case from Southeast Asia, which could expand the facial phenotypes of this rare syndrome, from a diverse population.…”

“…Given clinical similarities of the phenotypes, caused by biallelic mutations of OTUD6B and heterozygous ZMIZ1 mutations, and that the present patient harbored genetic defects of these two genes, we compared the phenotypes of the present patient to those in previous reports, as summarized in Table 1 [5][6][7][8][9][10][11][12].…”

“…In 2017, Autosomal recessive mutations of OTUD6B were first described to cause intellectual disability associated with seizure, dysmorphic features, and congenital malformations, including distal limb abnormalities. Some studies propose clinical similarities between OTUD6B-related phenotypes and Rubinstein-Taybi syndrome and Kabuki syndrome [5][6][7]. However, at present, phenotypic and genotypic data related to OTUD6B are still limited [5][6][7][8][9][10].…”

“…Some studies propose clinical similarities between OTUD6B-related phenotypes and Rubinstein-Taybi syndrome and Kabuki syndrome [5][6][7]. However, at present, phenotypic and genotypic data related to OTUD6B are still limited [5][6][7][8][9][10].…”