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Cecinio Ronquillo, Paul S Bernstein; Penetrance Estimation of Macular Telangiectasia Type 2 (MacTel) from Families in Utah and Idaho. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2016.
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Macular telangiectasia (MacTel) is an adult-onset autosomal dominant disease with reduced penetrance. Here, we a) describe newly-identified families affected with MacTel; b) determine disease penetrance estimates by sibling and parent analysis; and c) highlight one of the probands who, at 21 years old, is one of the youngest reported to have MacTel.
From a total of more than 50 probands identified from clinical records in Utah and Idaho, 23 were clinically phenotyped, diagnosed with MacTel and confirmed by the London Reading Centre. Clinical phenotyping included a baseline eye exam, OCT of the macula, fluorescein angiography, fundus autofluorescence and measurement of macular pigment density. If p is the penetrance probability of a candidate gene causing MacTel and under the assumption that this disease is very rare, the probability that a sibling or parent is affected was calculated to be p/2.
For 15 of the probands, there were a total of 51 siblings. Of the 44 siblings who were clinically phenotyped, 9 were diagnosed with MacTel. Four probands had both parents clinically phenotyped and only 1 out of the 4 probands did not have either of the parents affected. Analysis shows vertical transmission of MacTel from both male and female in 3 of our families suggesting an autosomal dominant disease. From our sibling data, we estimate the penetrance to be 0.41 (standard error: 0.12, 95% CI: 0.17, 0.65). From analysis of our parent data, an unbiased estimate of penetrance is 0.75. With such a small sample, formal analysis is not advised. Finally, one of our probands, a 21-year-old male shows the characteristic clinical appearance of MacTel with decreased macular pigment and telangiectatic parafoveal capillaries.
Our results show that the penetrance of MacTel is 41% by sibling analysis and 75% by parent analysis. Sibling penetrance may be a low estimate because some of the siblings may still be too young to exhibit symptoms. Also, the current teaching that MacTel is an age-related disease is now being challenged with diagnosis in younger individuals.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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