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Importance Autosomal recessive inherited neurodevelopmental disorders are highly heterogeneous, and many, possibly most, of the disease genes are still unknown. Objectives To promote the identification of disease genes through confirmation of previously described genes and presentation of novel candidates and provide an overview of the diagnostic yield of exome sequencing in consanguineous families. Design, Setting, and Participants Autozygosity mapping in families and exome sequencing of index patients were performed in 152 consanguineous families (the parents descended from a same ancestor) with at least 1 offspring with intellectual disability (ID). The study was conducted from July 1, 2008, to June 30, 2015, and data analysis was conducted from July 1, 2015, to August 31, 2016. Results Of the 152 consanguineous families enrolled, 1 child (in 45 families [29.6%]) or multiple children (107 families [70.4%]) had ID; additional features were present in 140 of the families (92.1%). The mean (SD) age of the children was 10.3 (9.0) years, and 171 of 297 (57.6%) were male. In 109 families (71.7%), potentially protein-disrupting and clinically relevant variants were identified. Of these, a clear clinical genetic diagnosis was made in 56 families (36.8%) owing to 57 (likely) pathogenic variants in 50 genes already established in neurodevelopmental disorders (46 autosomal recessive, 2 X-linked, and 2 de novo) or in 7 previously proposed recessive candidates. In 5 of these families, potentially treatable disorders were diagnosed (mutations in PAH , CBS , MTHFR , CYP27A1 , and HIBCH ), and in 1 family, 2 disease-causing homozygous variants in different genes were identified. In another 48 families (31.6%), 52 convincing recessive variants in candidate genes that were not previously reported in regard to neurodevelopmental disorders were identified. Of these, 14 were homozygous and truncating in GRM7 , STX1A , CCAR2 , EEF1D , GALNT2 , SLC44A1 , LRRIQ3 , AMZ2 , CLMN , SEC23IP , INIP , NARG2 , FAM234B , and TRAP1 . The diagnostic yield was higher in individuals with severe ID (35 of 77 [45.5%]), in multiplex families (42 of 107 [39.3%]), in patients with additional features (30 of 70 [42.9%]), and in those with remotely related parents (15 of 34 [44.1%]). Conclusions and Relevance Because of the high diagnostic yield of 36.8% and the possibility of identifying treatable diseases or the coexistence of several disease-causing variants, using exome sequencing as a first-line diagnostic approach in consanguineous families with neurodevelopmental disorders is recommended. Furthermore, the literature is enriched with 52 convincing candidate genes that are awaiting confirmation in independent families.

Non-specific intellectual disability of autosomal recessive inheritance (NS-ARID) represents an important fraction of severe cognitive dysfunction disorders. To date, only 10 genes have been identified, and further 24 linked-ARID loci have been reported, as well as others with suggestive linkage. To discover novel genes causing NS-ARID, we undertook genome-wide homozygosity mapping in 64 consanguineous multiplex families of Syrian descent. A total of 11 families revealed unique, significantly linked loci at 4q26-4q28 (MRT17), 6q12-q15 (MRT18), 18p11 (MRT19), 16p12-q12 (MRT20), 11p15 (MRT21), 11p13-q14 (MRT23), 6p12 (MRT24), 12q13-q15 (MRT25), 14q11-q12 (MRT26), 15q23-q26 (MRT27), and 6q26-q27 (MRT28), respectively. Loci ranged between 1.2 and 45.6 Mb in length. One family showed linkage to chromosome 8q24.3, and we identified a mutation in TRAPPC9. Our study further highlights the extreme heterogeneity of NS-ARID, and suggests that no major disease gene is to be expected, at least in this study group. Systematic analysis of large numbers of affected families, as presented here, will help discovering the genetic causes of ID.

Celebrity Endorsement, a tool used by several organisations, has today helped to attract customers so as to build a stronger image. Charisma, achievements and ethical actions are some of the traits of good endorsers. This paper is an effort to establish the relationship between Celebrity Endorsement and Brand Knowledge. This research considered two big brands in the sports apparel industry – Adidas and Nike. The aim was to determine whether there was a difference in the Brand Knowledge of Adidas and Nike consumers when impacted by Celebrity Endorsement. For this purpose, the Brand Knowledge of the respondents was assessed as well as how the latter perceived celebrity endorsers. This study adopted a quantitative survey methodology by distributing digital questionnaires. The study revealed that there was a relationship between Celebrity Endorsement and Brand Knowledge and also, although no significant difference in the Brand Knowledge of Nike and Adidas consumers was recorded earlier, however, when impacted by Celebrity Endorsement, their Brand Knowledge differed. The paper contributes to the creation of knowledge such as understanding the complexity and impacts of Celebrity Endorsement in more depths. Managers of Nike and Adidas could use this knowledge to enhance their endorsement strategies. While previous research focused on other impacts of Celebrity Endorsement, this paper attempted to shed light in an unexplored area.