Analysis
Case: MOL0369 Proband
CasePresentingHPOsFreeText: The ocular diagnosis was determined using a full ophthalmologic examination; full-field electroretinography; electro-oculography; color vision testing using the Panel D-15 test; optical coherence tomography; color, infrared, and fundus autofluorescence imaging; and fluorescein angiography, as detailed previously. The index case (patient II:1) received a diagnosis of RP at 20 years of age following complaints of impaired night vision and constricted visual fields. At 32 years of age, her electroretinographic responses were nondetectable (Table 1). At 49 years of age, her visual acuity (VA) was at the level of hand motions, and posterior polar cataract and posterior subcapsular opacity were evident. Fundus findings were compatible with advanced RP, including moderate pallor of the optic disc, widespread atrophy, and pigmentary changes. Optical coherence tomography revealed severe thinning of the outer nuclear layer and the epiretinal membranes. By 53 years of age, her VA decreased to the level of light perception with partial projection in both eyes. Her medical health record includes carcinoma of the cervix, which was diagnosed when she was 47 years of age and treated surgically with no sequela. She has mild hypertension, which is controlled by medication, and mild reflux. The results of a hearing test performed when she was 48 years of age were normal.
CasePreviousTesting: WES
CaseGenotypingMethod: we performed a series of mutation analyses, including APEX (arrayed primer extension)–based screening of all known RP mutations (http://www.asperbio.com/asper-ophthalmics) and screening for a set of mutations that we previously identified in patients with RP of the same origin (including mutations in the following genes: ABCA4, AIPL1, DHDDS, EYS, GUCY2D, NR2E3, RAB28, RPE65, and USH2A), Whole-exome sequencing evaluations for patients from 2 families (MOL0369
Variant: A subsequent analysis of other genes associated mainly with syndromic RP revealed the identification of 2 novel heterozygous missense variants in BBS2 (c.98C>A leading to p.A33D and c.401C>G leading to p.P134R) within the largest shared heterozygous region (Table 1). A segregation analysis showed that the mutations are in trans (ie, compound heterozygous mutations) and perfectly cosegregated with the disease
ClinVarID: or CAID: CA204968, CA204970
gnomAD: CA204968: allele frequency of 0.000002543 in the eurpoean non finnish population (v4.0.0); CA204970: allele frequency of 0.00002204 in the eurpoean non finnish population (v4.0.0)
AddCaseInfo:
FamilyName: MOL0369
Ethnicity: nonconsanguineous Moroccan Jewish family
Affected: 3
Unaffected:
Segregations:
eLOD:
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