Pedigree screening of a Chinese multiple endocrine neoplasia type 2A family and prophylactic total thy-roidectomy / 中华内分泌外科杂志

Objective To explore the clinical significance of integrated screening of RET in a Chinese multiple endocrine neoplasia type 2A(MEN 2A)family and to evaluate the feasibility and effectiveness of prophy-lactic total thyroidectomy to MEN 2A-related medullary thyroid carcinoma ( MTC).Methods Medical history was obtained from 10 family members in a 3-generation south China family .Systemic investigations including bio-chemical tests, imaging examinations and germline RET screening were performed .3 asymptomatic mutation car-riers underwent prophylactic total thyroidectomy .Results RET screening showed a heterozygous missense muta-tion of TGC to CGC at codon 634 on exon 11 in 6 members(p.C634R), which was completely consistent with the clinical manifestations.There were 4 males and 2 females.The initial mean diagnostic age of 33.5 years(ranging from 19 years to 65 years) and the mean maximum diameter of MTC was 2.3 cm(ranging from 0.7 cm to 5.2 cm). Among them 3 members had palpable neck masses (1 case with diarrhea).Right total thyroidectomy +right level Ⅵlymph-node dissection with modified right neck dissection in one case , and bilateral total thyroidectomy +bilat-eral level Ⅵlymph-node dissection in 2 were performed .In other 3 asymptomatic mutation carriers , prophylactic total thyroidectomy +bilateral level Ⅵ lymph-node dissection were also performed .Among them, 1 case of a-symptomatic pheochromocytom ( PHEO) underwent cortical-sparing adrenalectomy before MTC .After the first op-eration, 4 patients still presented a high value of calcitonin , among whom 1 patient( T3N 1bM 0-1) underwent re-operation for 3 times after the initial operation and presented metastasis to bone after 130 months, taking vandet-anib orally up to now;2 patients underwent reoperation at 6 and 7 months after initial operation respectively (T1N 1bM0 and T2N 1bM0), and the other one patient was closely monitored and followed up for 22 months(T2N 1b M0).Moreover, The calcitonin levels dropped to normal in the other 2 asymptomatic cases(T1N0M0) who were followed up for 20 months.Conclusions Pedigree screening can work up an early diagnosis and improve the prognosis of MEN 2A.Integrated screening of RET and pre-operative calcitonin level measurement and prophylac-tic thyroidectomy for asymptomatic RET mutation carriers are reasonable and effective .

Multiple endocrine neoplasia type 2A caused by a p.C618R RET proto-oncogene mutation in a Chinese pedigree / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the clinical characteristics and significance of RET proto-oncogene screening in multiple endocrine neoplasia type 2A (MEN2A).</p><p><b>METHODS</b>Comprehensive medical history was obtained for 5 members from a 3-generation family from southern China. Clinical investigations have included biochemical testing, imaging, and screening of germline RET proto-oncogene mutations.</p><p><b>RESULTS</b>Genetic screening has revealed a missense mutation at codon 618(TGC>CGC) of exon 10 in 3 patients(p.C618R), which was consistent with their clinical manifestations. For the 3 individuals, the age at diagnosis was 21, 26 and 36 yr, and the maximum diameter of medullary thyroid carcinoma was 22, 25 and 39 cm, respectively. The 36-year-old female patient initially underwent right total thyroidectomy plus right neck lymph node dissection. Four years later, she again underwent left adrenal tumorectomy and left total thyroidectomy plus left neck lymph node dissection. The 21-year-old male patient underwent right total thyroidectomy plus right modified neck dissection. The follow-up was respectively 146 and 26 months following the initial operation. Two patients still presented elevated calcitonin and had bilateral neck lymph node masses and/or left thyroid masses on imaging examination. The 26-year-old female patient, who presented bilateral thyroid masses and elevated calcitonin, has refused thyroidectomy.</p><p><b>CONCLUSION</b>Combined family survey and RET gene screening can facilitate early diagnosis and surgical treatment to improve the prognosis.</p>

KRT 9 Gene Mutations in Three Chinese Pedigrees with Epidermolytic Palmoplantar Keratoderma / 中华皮肤科杂志

Objective To investigate the keratin 9 gene mutation in epidermolytic palmoplantar keratoderma (EPPK) and its relationship with clinical manifestations. Methods Three Chinese pedigrees with EPPK were studied. Polymerase chain reaction (PCR) was performed to amplify the seven exons encoded by keratin 9. Denaturing high-performance liquid chromatography (DHPLC), DNA sequencing and allele-specific PCR were used to reveal the sequence variation in the PCR products. Results An insertion-deletion mutation in the exon 1 of keratin 9 497delAinsGGCT, was revealed in all 3 EPPK families, resulting in the keratin 9 change from tyrosine166 to tryptophan and leucine (Y166delinsWL). Allele-specific PCR confirmed that the mutation was not a commonly seen polymorphism, but a novel mutation which has not been reported in The Human Intermediate Filament Mutation Database (http://www.interfil.org). Conclusions A new keratin 9 gene mutation, 497delAinsGGCT, is found in these Chinese EPPK pedigrees, which may be the genetic basis of EPPK.