Haplotype analysis.

<p>Four microsatellite markers (D10S197, D10S196, D10S1652 and D10S537) from 9 related members (II-5, II-6, III-10, III-11, III-12, III-13, III-15, IV-10 and IV-11) demonstrated that the p.C634Y/V292M/R67H/R982C mutation did not arise on a common chromosome; p.C634Y was of maternal origin and p.V292M/R67H/R982C was paternal and located in a common allele.</p

Clinical presentations of PHEO with <i>RET</i> mutations.

<p>F, female; M, male; Mat, maternal family; DA, dopamine; E, epinephrine; NE, norepinephrine; L, left; R, right; AT, adrenalectomy; Bi-, Bilateral.</p

Portion of DNA sequences and polyacrylamide gel electrophoresis analysis of restriction endonuclease digestion.

<p>A, Maternal origin MEN 2A (III-23, III-12 and IV-10) were heterozygous for c.G2901A (p.C634Y), whereas paternal origin members (III-11, III-6, II-5, II-6 and III-3) were homozygous for the wild-type allele. This mutation was confirmed by <i>Kpn</i> I digestion. B, IV-10 and paternal origin FMTC (III-11, II-5, and III-3) demonstrated a heterozygous c.G874A (p.V292M) mutation which created the restriction enzyme site for <i>Nco</i> I, whereas maternal origin members (III-12 and IV-11), and two unaffected paternal members (III-10 and IV-8) showed the normal sequence. C, A heterozygous c.C2944T (p.R982C) polymorphism from IV-10 and paternal origin FMTC (III-11, II-5 and III-3) was found, whereas the maternal origin members III-12 and IV-11 and two unaffected paternal members (III-10 and IV-8) were homozygous for the wild-type allele. This polymorphism was validated by <i>Rsa</i> I digestion.</p

Summary of reported <i>RET</i> double mutations associated with MEN 2.

<p>Summary of reported <i>RET</i> double mutations associated with MEN 2.</p

Clinical presentations of patients with MTC and <i>RET</i> mutations.

<p>*proband; F, female; M, male; Pat, paternal family; Mat, maternal family; Pre-op Ct, pre-operative calcitonin (ng/L); US, ultrasound; AS, awaiting surgery; ADM, age at diagnosis of MTC; pTNM, tumour stage; TT, total thyroidectomy; Bi-, Bilateral; No spec, no specimen.</p>a<p>LN+ includes positive lymph nodes proven on histopathology; resected includes lymph node resected.</p

Portion of genomic DNA and RT-PCR product sequencing from tumor tissues.

<p>A, Direct sequencing consequences of RT-PCR products from PHEO tissue of III-12 indicated a heterozygous G/A mutation at codon 634, which was consistent with the results of DNA from blood and tumor tissues and whole exome sequencing. B, C, D, Direct sequencing consequences of RT-PCR products from MTC tissue of III-11 indicated heterozygous G/A, C/T, and G/A mutations at codons 292, 982, and 67, respectively, which was consistent with the results of DNA from blood and tumor tissues and whole exome sequencing.</p