M144NS COQ5 G118S1.815.10P, E; methyltransferase with pivotal role in coenzyme Q biosynthesis. Interacts with NAB2 which controls length of poly(A) tail (see http://thebiogrid.org/35094/summary/saccharomyces-cerevisiae/coq5.html). The human orthologue of NAB2 is implicated in ARID32.

Patient historyWe present a Polish female patient current age 10 years, born at term by natural delivery at the 39th week of the mother’s first pregnancy. Parents were healthy, non-consanguineous, Caucasian in origin. At the time of birth, the mother was 29 years old; the father was 33 years old.Family history was negative for individuals with neurodevelopmental disorders. Patient birth body parameters were the following: body weight: 3380 g (50 pc); body length: 54 cm (<95 pc); occipital frontal circumference: 31 cm (<3 pc). Apgar scores were 10 points at 1 and 5 min of life.Presented girl displayed normal, uneventful postnatal adaptation and development from birth to 5 months of life.At 22 weeks, directly after third dose-vaccination with DTaP (Infanrix-Hexa), motor and cognitive regression, deterioration of eye contact, and the lack of a smile were noticed. Consequently, further vaccinations were suspended. At the age of 18 months, further developmental regression became apparent. She was intensively rehabilitated, but no progress was observed. In clinical evaluation, she could not stand up or walk independently and she could pronounce a few simple syllables and try to combine them into words. Detailed clinical observations from 1.5 to 10 years of age are described in supplementary data.At the age of 10 years, she had not acquired the ability to walk; cognitive development remains at a low level. Summary of neurological examinations showed global developmental delay, tetraparesis with hypotonia and symmetrical tendon reflexes, limited eye contact, postural defects including a “rounded” back, protruding shoulder blades, and funnel-shaped chest (Fig. ​(Fig.1aIII–IV).1aIII–IV). Phenotypic evaluation of the face revealed slight ptosis, a tendency to open the mouth and tilt the head back, without other specific features of dysmorphism (Fig. ​(Fig.11aI).Open in a separate windowFig. 1a Photographic documentation of the patient at age 10 years old. b COQ5 cDNA gel electrophoresis. c Graphical representation of the splicing products of the COQ5 gene in a patient, her parents, and healthy control. For more details, please see supplementary dataExploratory assaysMagnetic resonance imaging (MRI) of the brain at the age of 8 years revealed clear cortico-subcortical atrophy of the cerebellum–enlargement of the 4th ventricle and widening of cerebellar sulci (Supp.Fig.1a-d, arrows) as compared to the normal appearance in a healthy individual (Supp.Fig.1e-h, arrows). The cerebellar sulci were wider in our patient at age 8 years than at 18 months, as well as in comparison to an age-matched healthy control. This indicates progressive atrophy of cerebellar tissue. Atrophy involved both vermis and cerebellar hemispheres. The supratentorial structures are normal. Echocardiogram, abdominal ultrasonography, and ophthalmologic investigation were also uneventful.