The objective of this study was the identification of likely genes and mutations associated with an autosomal recessive (AR) rare spinocerebellar ataxia (SCA) phenotype in two patients with infantile onset, from a consanguineous family. Using genome-wide SNP screening, autozygosity mapping, targeted Sanger sequencing and nextgen sequencing, family segregation analysis, and comprehensive neuropanel, we discovered a novel mutation in SPTBN2. Next, we utilized multiple sequence alignment of amino acids from various species as well as crystal structures provided by protein data bank (PDB# 1WYQ and 1WJM) to model the mutation site and its effect on β-III-spectrin. Finally, we used various bioinformatic classifiers to determine pathogenicity of the missense variant. A comprehensive clinical and diagnostic workup including radiological exams were performed on the patients as part of routine patient care. The homozygous missense variant (c.1572C>T; p.R414C) detected in exon 2 was fully segregated in the family and absent in a large ethnic cohort as well as publicly available data sets. Our comprehensive targeted sequencing approaches did not reveal any other likely candidate variants or mutations in both patients. The two male siblings presented with delayed motor milestones and cognitive and learning disability. Brain MRI revealed isolated cerebellar atrophy more marked in midline inferior vermis at ages of 3 and 6.5 years. Sequence alignments of the amino acids for β-III-spectrin indicated that the arginine at 414 is highly conserved among various species and located towards the end of first spectrin repeat domain. Inclusive bioinformatic analysis predicted that the variant is to be damaging and disease causing. In addition to the novel mutation, a brief literature review of the previously reported mutations as well as clinical comparison of the cases were also presented. Our study reviews the previously reported SPTBN2 mutations and cases. Moreover, the novel mutation, p.R414C, adds up to the literature for the infantile-onset form of autosomal recessive ataxia associated with SPTBN2. Previously, few SPTBN2 recessive mutations have been reported in humans. Animal models especially the β-III mouse model provided insights into early coordination and gait deficit suggestive of loss-of-function. It is expected to see more recessive SPTBN2 mutations appearing in the literature during the upcoming years.

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Background: Nurturing a child with Autism Spectrum Disorder (ASD) can cause major distress. As a result, these parents tend to experience a poor quality of life (QoL) compared to those raising typically developing (TD) children. Objectives: To evaluate the factors which affect the QoL of parents raising children clinically-diagnosed with ASD in Jeddah, and to provide knowledge for the establishment of comprehensive policies and projects that can improve their mental well-being. Materials and Methods: A cross-sectional study design was utilized to assess 200 parents of children clinically-diagnosed with ASD at least 3 months prior to the research. A self-administered WHOQOL-BREF questionnaire was employed to assess the QoL of participants through four domains, namely physical health, psychological well-being, social relationships, and environment. Results: Most of the participants were female (58.5%), married (87.0%), and employed (56.5%). Majority completed high school (68.5%), lived in the city (95.5%) and rented their homes (88.5%). Quality of life was significantly affected by gender, employment, social status, and educational attainment of participants. Parents with higher educational attainment and employment and social status exhibited better. Furthermore, female parents experienced lower QoL and more depressive symptoms than males. Conclusion: Gender, educational attainment, and both employment and social status significantly affected the QoL of parents raising children diagnosed with ASD. Furthermore, improving the physical health, psychological, social relationships, and environment of these parents would give them a better QoL and health satisfaction.