Peripherin mutations cause a distinct form of recessive Leber congenital amaurosis and dominant phenotypes in asymptomatic parents heterozygous for the mutation.
PMID 26061163 | DOI 10.1136/bjophthalmol-2015-306844 · The British journal of ophthalmology · 2016
BACKGROUND: Dominant mutations in peripherin (PRPH2) are associated with a spectrum of retinal dystrophy phenotypes, many of which are adult onset and involve the macula. Recessive PRPH2 mutations cause retinal dystrophy associated with prominent maculopathy in adulthood; however, the presenting childhood phenotype has not been defined. We characterise this phenotype. METHODS: Retrospective case series of families harbouring bi-allelic PRPH2 mutations (2010-2014). RESULTS: Three children (two families; assessed at 2 years old) and two adults (one family; assessed at 24 and 35 years old) with homozygous PRPH2 mutations (c.497G>A (p.Cys166Tyr) or c.136C>T (p.Arg46*)) all had infantile nystagmus and decreased vision noted soon after birth and a history of staring at lights during infancy (photophilia). The three children had high hyperopia, a normal or near normal fundus, and non-recordable electroretinographies (ERGs). The two adults had slight myopia, macular and peripheral retinal changes, and non-recordable ERGs. All five available carrier parents had macular±peripheral retinal findings, although they considered themselves asymptomatic except for one mother who had developed visual loss in one eye at 48 years old and had an associated subfoveal lesion. CONCLUSIONS: Bi-allelic PRPH2 mutations cause a distinct Leber congenital amaurosis phenotype in infancy; affected adults have prominent maculopathy. Heterozygous parents can be asymptomatic but have clinically obvious macular phenotypes with or without peripheral retinal findings, which can be helpful in making the genetic diagnosis in affected children. The difference between the heterozygous and homozygous phenotypes is likely related to gene product dosage effect.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | PRPH2 | “BACKGROUND: Dominant mutations in peripherin (PRPH2) are associated with a spectrum of retinal dystrophy phenotypes, many of which are adult onset and involve the macula.” | 0.98 | hgnc_dict_v1 |
| phenotype | Leber congenital amaurosis | “Peripherin mutations cause a distinct form of recessive Leber congenital amaurosis and dominant phenotypes in asymptomatic parents heterozygous for the mutation.” | 0.98 | phenotype_alias_lexicon_v2 |
| phenotype | retinal dystrophy | “BACKGROUND: Dominant mutations in peripherin (PRPH2) are associated with a spectrum of retinal dystrophy phenotypes, many of which are adult onset and involve the macula.” | 0.98 | phenotype_alias_lexicon_v2 |
| variant | c.497G>A | “RESULTS: Three children (two families; assessed at 2 years old) and two adults (one family; assessed at 24 and 35 years old) with homozygous PRPH2 mutations (c.497G>A (p.Cys166Tyr) or c.136C>T (p.Arg46*)) all had infantile nystagmus and decreased vision noted soon after birth and a history of staring at lights during infancy (photophilia).” | 0.95 | hgvs_regex_v1 |
| variant | p.Cys166Tyr | “RESULTS: Three children (two families; assessed at 2 years old) and two adults (one family; assessed at 24 and 35 years old) with homozygous PRPH2 mutations (c.497G>A (p.Cys166Tyr) or c.136C>T (p.Arg46*)) all had infantile nystagmus and decreased vision noted soon after birth and a history of staring at lights during infancy (photophilia).” | 0.95 | hgvs_regex_v1 |
| variant | c.136C>T | “RESULTS: Three children (two families; assessed at 2 years old) and two adults (one family; assessed at 24 and 35 years old) with homozygous PRPH2 mutations (c.497G>A (p.Cys166Tyr) or c.136C>T (p.Arg46*)) all had infantile nystagmus and decreased vision noted soon after birth and a history of staring at lights during infancy (photophilia).” | 0.95 | hgvs_regex_v1 |
| variant | p.Arg46* | “RESULTS: Three children (two families; assessed at 2 years old) and two adults (one family; assessed at 24 and 35 years old) with homozygous PRPH2 mutations (c.497G>A (p.Cys166Tyr) or c.136C>T (p.Arg46*)) all had infantile nystagmus and decreased vision noted soon after birth and a history of staring at lights during infancy (photophilia).” | 0.95 | hgvs_regex_v1 |