Individuals born of consanguineous union have segments of their genomes that are homozygous as a result of inheriting identical ancestral genomic segments through both parents. One consequence of this is an increased incidence of recessive disease within these sibships. Theoretical calculations predict that 6% (1/16) of the genome of a child of first cousins will be homozygous and that the average homozygous segment will be 20 cM in size. We assessed whether these predictions held true in populations that have preferred consanguineous marriage for many generations. We found that in individuals with a recessive disease whose parents were first cousins, on average, 11% of their genomes were homozygous (n = 38; range 5%-20%), with each individual bearing 20 homozygous segments exceeding 3 cM (n = 38; range of number of homozygous segments 7-32), and that the size of the homozygous segment associated with recessive disease was 26 cM (n = 100; range 5-70 cM). These data imply that prolonged parental inbreeding has led to a background level of homozygosity increased approximately 5% over and above that predicted by simple models of consanguinity. This has important clinical and research implications.
Drusen are discussed frequently in the context of their association with age-related macular degeneration (AMD). Some types may, however, be regarded as a normal consequence of ageing; others may be observed in young age groups. They also occur in a number of inherited disorders and some systemic conditions. Whilst drusen are classically located external (sclerad) to the retinal pigment epithelium, accumulations of material internal (vitread to) this layer can display a drusen-like appearance, having been variously termed pseudodrusen or subretinal drusenoid deposits. This review first briefly presents an overview of drusen biogenesis and subclinical deposit. The (frequently overlapping) subtypes of clinically detectable deposit, seen usually in the context of ageing or AMD, are then described in more detail, together with appearance on imaging modalities: these include hard and soft drusen, cuticular drusen, reticular pseudodrusen and "ghost drusen". Eye disorders other than AMD which may exhibit drusen or drusen-like features are subsequently discussed: these include monogenic conditions as well as conditions with undefined inheritance, the latter including some types of early onset drusen such as large colloid drusen. A number of systemic conditions in which drusen-like deposits may be seen are also considered. Throughout this review, high resolution images are presented for most of the conditions discussed, particularly the rarer ones, providing a useful reference library for images of the range of conditions associated with drusen-like appearances. In the final section, some common themes are highlighted, as well as a brief discussion of some future avenues for research.
Ophthalmic complications of COVID-19 are predicted based on prior knowledge of other coronaviruses [1]. Conjunctivitis can be the presenting sign/symptom and its presence correlates with severity [2-4]. Cotton wool spots and retinal microhaemorrhages have also been reported [5]. We report two patients who presented with a new paracentral scotoma following SARS-CoV-2 infection. Patient 1: A 37-year-old Caucasian female in week 14 of an uncomplicated pregnancy presented with a 1-day history of abrupt onset, faintly colourful, left eye paracentral scotoma. This was 35 days following the onset of a febrile illness with cough and anosmia. SARS-CoV-2 nasopharyngeal swab was not performed during the infection, but subsequently positive serology (IgG) has been confirmed. Past medical history included acephalgic visual migraine aura and right toxoplasma chorioretinitis. Examination showed normal visual acuity, no uveitis and fundoscopy was normal in the left eye. OCT changes correlated with the location of the scotoma (Fig. 1). A focal area of hyper-reflective change in the inner and outer plexiform layers with inner nuclear layer volume loss was seen consistent with paracentral acute middle maculopathy (PAMM). Bloods were normal, including ESR, CRP, lipids, glucose, ANA and anti-phospholipid antibodies. An electrocardiogram and carotid Doppler ultrasound were normal. Patient 2: A 32-year-old Caucasian male presented with a 4-day history of abrupt onset, faintly colourful, right eye paracentral scotoma. This was 16 days following the onset of nasopharyngeal swab confirmed COVID-19. Past medical history included acephalgic visual migraine aura.
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