Genetics of Primary Inherited Disorders of the Optic Nerve: Clinical Applications

Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity

“…Indeed, PCG accounts for 18% of children enrolled in institutions for the blind worldwide (7). PCG occurs in all ethnic groups, but the disease incidence varies according to ethnic background, ranging from 1:1,250 in inbred populations to 1:30,000 in populations with heterogeneous ethnicity (6,(8)(9)(10)(11)(12). Families can exhibit autosomal recessive or dominant inheritance, although the majority of cases appear to be sporadic (5,6,(10)(11)(12)(13)(14).…”

“…The molecular etiology of PCG is only partially understood, as only a few genes responsible for PCG have been identified (6,(10)(11)(12)(13)(14). Mutations in CYP1B1, which encodes a cytochrome P450 enzyme, is the most common cause of autosomal recessive PCG worldwide, accounting for up to 87% of familial cases in some inbred populations but only 25%-27% in populations with heterogeneous ethnicity (5, 9, 15-18).…”

Exome sequencing identified a novelde novo OPA1mutation in a consanguineous family presenting with optic atrophy

“…Non-syndromic recessive optic atrophy is a rare form of optic neuropathy. To date, only two genes (TMEM126A and ACO2) and one locus (8q) have been identified (Allen et al, 2015). The main forms of non-syndromic optic atrophy are depicted in Table 1.…”

“…Optic atrophy can be isolated or associated with multi-systemic involvement (syndromic; Allen et al, 2015) such as in Costeff's syndrome (methyl-glutaconic aciduria type 3; OMIM 258501; Ho et al, 2008), Behr's syndrome (OMIM 210000; Pyle et al, 2014) or Wolfram syndrome (OMIM 598500;Safarpour et al, 2016). While multiple modes of inheritance have been reported, autosomal dominant optic atrophy (ADOA) and mitochondrial inherited Leber's hereditary optic neuropathy (LHON) are the most common forms (Pfeffer et al, 2013;Skidd et al, 2013).…”

La neuropatia ottica ereditaria di Leber (Leber Hereditary Optic Neuropathy, LHON)

“…Tuttavia, l'epidemiologia della LHON non è ancora correttamente definita non solo per la rarità della patologia, ma anche per aspetti peculiari della malattia che possono tradursi in una variabilità delle osservazioni. Per esempio, la penetranza incompleta spiegherebbe perché, tra i portatori della mutazione genica, solo il 50% dei maschi e il 10% delle femmine sviluppa la malattia; fattori anatomici [13], ambientali, abitudi ni di vita (tipicamente il fumo) [14][15][16][17][18] [32]). Dopo il raggiungimento del plateau di ri-stione della terapia con idebenone nei pazienti con diagnosi di LHON.…”