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. 2013 Jun 27;368(26):2532-4.
doi: 10.1056/NEJMc1300278.

Germline mutations affecting Gα11 in hypoparathyroidism

Michael Mannstadt, Mark Harris, Bert Bravenboer, Sridhar Chitturi, Koen M A Dreijerink, David G Lambright, Elaine T Lim, Mark J Daly, Stacey Gabriel, Harald Jüppner

Germline mutations affecting Gα11 in hypoparathyroidism

Michael Mannstadt et al. N Engl J Med. .
No abstract available

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Figures

Figure 1
Figure 1. Pedigrees and Laboratory and Genetic Findings for Two Families with Autosomal Dominant Isolated Hypoparathyroidism
Squares indicate male family members, circles female family members, black symbols affected family members, and white symbols unaffected family members; slashes indicate deceased family members; numbers outside squares and circles indicate family members for whom DNA was available for testing; numbers within white rhombi indicate the number of unaffected siblings. Arrows point to the index cases. Measurements for calcium, phosphorus, and parathyroid hormone (PTH) are shown (with adult normal ranges in parentheses) and reflect values at presentation except in the case of Patients 21 and 32, from whom samples were drawn after treatment was initiated. For affected members, mean (±SE) pretreatment serum levels of calcium were 2.15±0.02 mmol per liter in Family A and 1.91±0.04 mmol per liter in Family B, mean levels of phosphorus were 2.06±0.40 and 1.79±0.13 mmol per liter, respectively, and mean levels of PTH were 1.97±0.42 and 1.33±0.27 pmol per liter, respectively. Values for other variables among patients with autosomal dominant isolated hypoparathyroidism for whom mean pretreatment levels were available were as follows: magnesium, 0.77±0.02 mmol per liter (10 patients; normal range, 0.7 to 1.0); 1,25-dihydroxyvitamin D, 81.8±10.0 pmol per liter (8 patients; normal range, 40 to 150); and urinary calcium:creatinine ratio, normal when measured (8 patients; normal range, <0.6 mmol:mmol). Two novel mutations affecting Gα11 (R60C and S211W) were identified by means of genetic linkage analysis for Family A and exome sequencing of a DNA sample from two affected members of Families A and B (see Fig. 1 in the Supplementary Appendix). Digestion of DNA (amplified by means of polymerase chain reaction) with the endonucleases FspI and BsiEI, respectively, confirmed the two mutations and revealed their segregation with the disease.
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