MRT5 is a neurodevelopmental disorder encompassing, in addition to delayed speech and psychomotor development, a number of dysmorphic features such as microcephaly, long and narrow face, bushy eyebrows with synophrys, hypotelorism, large nose with long columella, short philtrum, and full upper lip. Many affected individuals have short stature, and some have later onset of muscular hypertonia and spasticity.
Diagnosis is made upon observing the aforementioned symptoms. Some patients can benefit from specific programs aimed at people with developmental disabilities to help them learn basic life skills.
Martinez et al. (2012) used exome sequencing to uncover a homozygous mutation in the NSUN2 gene in two Lebanese sibs with developmental delay and dysmorphic features. These sibs were born to consanguineous parents living in the UAE. The novel mutation deletes the splice acceptor site of exon 6 leading to mRNA instability and lack of NSUN2 protein in patient cells.
Komara et al. (2015) described a 17-year-old Emirati male suffering from intellectual disability. The patient, born to first-degree consanguineous parents, lacked speech and exhibited severe hyperactivity, disruptive and self-harming behavior, a broad gait and mild cerebellar atrophy. He suffered from severe osteoporosis and had a history of recurring falls causing fractures. His height and weight were below the 3rd centile. Facial dysmorphia included a small head with brachycephaly, downslanting palpebral fissures, flat maxilla, prominent nasal bridge with long nose, columella extend below the nares, smooth philtrum, and a large open mouth with a downturning upper lip. He had small testes with a low testosterone level and showed no signs of puberty. Whole exome sequencing helped identify a novel homozygous deletion (c.1020delA) in exon 9 of the patient’s NSUN2 gene, which was predicted by MutationTaster to be pathogenic. The mutation was shown to result in a frameshift and premature termination (G341Vfs*). Further, the patient had decreased levels of NSUN2 mRNA compared to a healthy control confirming nonsense mediated decay.
[See also: Lebanon > Martinez et al., 2012].