Centre for Arab Genomic Studies a Division of Sheikh Hamdan Award for Medical Sciences

Centre for Arab Genomic Studies A Division of Sheikh Hamdan Award for Medical Sciences

The Catalogue for Transmission Genetics in Arabs CTGA Database

Rotatin

Alternative Names been associated with MSSP. These include RTTN multiple transversions and transitions resulting in amino acid substitutions at highly conserved Record Category residues and an insertion (c.2885+8A-G) resulting Gene locus in a premature stop codon (S963X).

WHO-ICD Epidemiology in the Arab World N/A to gene loci Saudi Arabia Incidence per 100,000 Live Births N/A to gene loci Shamseldin et al. (2015) reported on two Arab MSSP affected families. Family 1 was a Yemeni OMIM Number consanguineous family with three affected siblings 610436 that showed severe short stature, microcephaly, craniofacial dysmorphism and intellectual Mode of Inheritance disability. In family 2, a 5.5-year-old Saudi N/A to gene loci Arabian boy, born to healthy consanguineous parents, was found to suffer from severe Gene Map Locus microcephaly with simple gyration, microcephalic 18q22.2 dwarfism, and craniofacial dysmorphism. Autozygome analysis and exome filtering for rare Description variants in family 1 uncovered an intronic variant Rotatin encodes a protein that is localized at the c.2885+8A>G in exon 23 of the RTTN gene ciliary basal bodies in human fibroblast cells. resulting in a premature stop codon S963X. While the exact function of Rotatin is yet to be Analysis of the Saudi Arabian child revealed a elucidated, it is predicted to play a key role in early homozygous c. 3190A>C mutation. The parents developmental processes such as axial rotation and and unaffected sisters were found to be left-right specification by maintaining ciliary heterozygous for the mutation. As the affected structure. It may also be involved in notochord lysine residue was conserved down to zebrafish, in- development. Mouse studies of homozygous situ analysis predicted this mutation to be highly RTTN null embryos have found to result in pathogenic. Both variants were not found in 1000 randomized heart looping, delayed neural tube Genomes, the ExAC Browser or control exomes. closure, axial rotation failure and eventually, Linkage analysis of families 1 and 2 revealed the embryonic death. This further confirms the only significant linkage peak to map to the RTTN importance of Rotatin in embryonic development. gene, further confirming the association of RTTN with this disorder. Mutations in RTTN have been associated with MSSP, a syndrome characterized by microcephaly, Yemen primordial dwarfism and polymicrogyria. [See: Saudi Arabia > Shamseldin et al., 2015] Molecular Genetics The RTTN gene is located on the long arm of References chromosome 18 and is made up of 54 exons. It Shamseldin H, Alazami AM, Manning M, Hashem encodes a 246 kDa protein that is made of 2226 A, Caluseiu O, Tabarki B, Esplin E, Schelley S, amino acids. Several homozygous and compound Innes AM, Parboosingh JS, Lamont R; Care4Rare heterozygous mutations in the RTTN gene have Canada Consortium, Majewski J, Bernier FP,

Alkuraya FS. RTTN Mutations Cause Primary External Links Microcephaly and Primordial Dwarfism in http://www.genecards.org/cgi- Humans. Am J Hum Genet. 2015; 97(6):862-8. bin/carddisp.pl?gene=RTTN

Related CTGA Records Contributors Microcephaly, Short Stature, and Polymicrogyria Sayeeda Hana: 23.7.2016 with or without Seizures