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Elise Heon, Sophie Qin, Helene Dollfus, Val Sheffield, Edwin M Stone, Gail Billingsley, Ajoy Vincent; Is C8orf37 the eighteenth BBS gene? A case report. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3271.
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To identify the disease causing mutation for a proband (Caucasian), part of a sibship of 3 and product of a consanguineous marriage who has the clinical features of BBS syndrome.
Direct sequencing using commercial panels for BBS genes and autosomal recessive retinitis pigmentosa (RP) from the Casey Eye Institute was performed. Validation of novel variations used the allele frequency data available from the publicly available databases. Familial segregation of the variation was also performed. Phenotype assessment included: comprehensive eye exam, color vision testing (HRR plates), Goldman Visual fields, abdominal ultrasound, brain MRI, echocardiogram and audiogram. In addition, electroretinography (ERG) was performed according to the ISCEV standards.
A novel homozygous pLys102stop C8orf37 mutation was identified in addition to a BBS4 K46R heterozygous variant. Her revised phenotype included: RP, obesity (BMI 30.1), learning difficulty, high myopia, 3 limb post-axial polydactyly, horseshoe kidney, retroflexed uterus and increased liver enzymes. At 14 years of age, the ERG supported the diagnosis of a rod cone dystrophy. Her visual acuity was 20/40 and her fields of vision were 20 degrees vertically and 60 degrees horizontally in each eye. She had no measurable color vision.
This is the first association of a full-blown BBS phenotype with C8orf37 mutations and appears to be an allelic variant of other C8orf37-related conditions. As other ciliary proteins have shown, mutations can lead to important phenotype heterogeneity. Considering that 2 patients with RP and mutations in C8orf37 were also reported to have polydactyly, patients with C8orf37 mutations should have a full workup to assess the presence of BBS features. It is unknown if the BBS4 heterozygous change is exerting a modifying influence on the C8orf37 mutation.
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