A de novo mutation in GNAS cause severe pseudohypoparathyroidism typeⅠa / 临床儿科杂志

Objective To identify the GNAS gene mutation resulting in pseudohypoparathyroidism type Ⅰa (PHP-Ⅰa) in one patient. Methods The clinical data of a patient with pseudohypoparathyroidism type Ⅰa was retrospectively analyzed. All the 13 exons of GNAS were sequenced using Sanger method for the patient and the parents. The distribution of suspected causal mutation was screened in 478 healthy controls. To clarify the origin of the mutation, we performed targeted high-depth sequencing of GNAS exon harboring the mutation for the patient and the parents. Results The clinical data of the patient with the laboratory results of hypocalcaemia, hyperphosphataemia, elevated serum PTH, together with the features of AHO, conformed to the characterization of PHP-Ⅰa. The sequencing of GNAS exons identified a missense mutation (c.479G>C, p.R160P) located at exon 6 in the patient, which was absent in DNA of the parents. The mutation was not reported previously and was not found in the 478 healthy controls. We obtained about 8000-fold coverage from high-depth sequencing of DNA from peripheral blood of the patient and the parents. The disease-associated allele C identified in the patient was not observed in the parents. The number of reads with G allele (3984 reads) was roughly equal to that of C allele (4019 reads) from the targeted reanalysis of DNA of the patient. The results from high-depth sequencing indicated a de novo mutation in maternal germ cells. Conclusions We identified a new GNAS gene mutation (c.479G>C, p.R160P) caused PHP-Ia in a patient. Our results suggested the mutation was a maternal germline de novo mutation.

Association between single nucleotide polymorphism in exon 33 of thyro-globulin gene and Graves ’ disease relapse after antithyroid drug with-drawal / 中国病理生理杂志

AIM:To explore the association between single nucleotide polymorphism in exon 33 (E33SNP) of thyroglobulin gene and Graves ’ disease ( GD) relapse after antithyroid drug ( ATD) withdrawal .METHODS:The healthy controls (232 cases) and GD patients with discontinued treatment (243 cases) were selected.According to the time of re-lapse, the GD patients were divided into A, B and C subgroups.The A group contained 77 cases of relapse within 1 year, B group contained 86 cases of relapse 1~2 years after treatment and C group contained 80 cases without recurrence within 2 years.The genotypes of E33SNP were identified by RT-PCR.The genotype ratio of thyroglobulin between control group and observation group was comparatively analyzed , and the levels of thyroid-stimulating hormone ( TSH) , free triiodothyro-nine (FT3), free thyroxine (FT4) and thyrotropin receptor antibody (TRAb), ophthalmopathy and goiter size in A , B and C subgroups in different genotype GD patients were investigated .Moreover , cumulative efficiency for patients with different genotypes in the observation group after ATD treatment within 2 years were analyzed .RESULTS:The genotype of E33SNP between observation group and control group had no significant difference , but a significant difference between A , B and C subgroups was observed (P<0.05).The levels of TSH, FT3 and FT4, and goiter size of the patients with different geno-types had no significant difference , while the TRAb levels and ophthalmopathy presented a significant difference ( P <0.05).In addition, the cumulative efficiency within 2 years for GD patients with E33SNP T/T, E33SNP T/C and E33SNP C/C genotypes was 61.8%, 42.6% and 21.3%, respectively, all with significant differences (P<0.05).CONCLU-SION:The GD patients with E33SNP C/C genotype have significantly higher TRAb level and ophthalmopathy rate than those in the patients with E33SNP C/T and E33SNP C/C genotypes, and are more likely to relapse after ATD treatment . The GD patients with E33SNP T/T genotype show a lower recurrence rate .Therefore, combination treatment or other treat-ment modalities may be more reasonable for the GD patients with E 33SNP C/C genotype.

Relevant factors in predicting the relapse of Graves disease after treatment with antithyroid drugs / 中华全科医师杂志

Objective To evaluate the prognostic factors of predicting the outcome of Graves disease (GD) after treatment with antithyroid drugs.MethodsA retrospective audit was performed for 306 consecutive patients with newly diagnosed GD.They were divided into successful and failure groups (including recurrent and non-stop subgroups )according to the treatment outcomes.Different prognostic factors after treatment with antithyroid drugs were compared and the state of thyrotropin suppression was observed as the euthyroid state at Months 3,6 and 12 respectively.ResultsAmong them,141patients (46.1％ ) were cured and 165 patients (53.9％) had treatment failures.Age at the time of diagnosis was (46 ±10) years in the successful group and (36 ±9) years in the failure group(t =3.152,P =0.002).Free T3 ( FT3 ) was (25.2 ±8.9) and ( 18.7 ±9.4) pmol/L in the failure and successful groups respectively (t =3.326,P =0.001).The FT3 to FT4 ratio and thyrotrophin receptor antibody (TRAb) levels were higher in the failure group ( t =3.331,3.389,P =0.001).Logistic regression analysis showed that thyroid size,FT3 to FT4 ratio and TRAb at the time of diagnosis were associated with failure outcomes.The ratio of continuing thyrotropin suppression in the recurrent subgroup was more than that in the successful group ( X2 =77.515,114.441,136.232,all P ＜ 0.01).ConclusionsThe GD patients with a large thyroid size and high pre-mediation levels of TRAb and FT3 to FT4 ratio are more prone to respond unfavorably to antithyroid drug treatment.And those with a large thyroid size and post-medication ophthalmopathy and continuing thyrotropin suppression have a high rate of recurrence.

High sensitive Serum C-reaction protein in macrovascular disease with or without type 2 diabetes / 中国康复理论与实践

@#ObjectiveTo observe the changes of high sensitive serum C-reaction protein (hsCRP) in macrovascular disease with or without type 2 diabetes.MethodsThere were 3 groups population in our study:148 type 2 diabetic patients were divided into 2 subgroups:77 patients with macrovascular disease and 71 without macrovascular disease, 73 non-diabetic patients with macrovascular disease and 75 health controls. The concentration of serum hsCRP of all patients were determined by ELISA.ResultsThere was significant difference in concentration of serum hsCRP between type 2 diabetes with or without macrovascular disease groups, non-diabetes macrovascular disease group and control(P<0.01 or P<0.001). However, there was not significant difference between 2 diabetes groups and non- diabetic macrovascular disease group(P>0.05). There was no significant difference in hsCRP between type 2 diabetes with and without macrovascular disease (P>0.05).ConclusionThere may be a chronic inflammatory reaction in patients with type 2 diabetes or macrovascular disease. hsCRP might be a well forecasting factor of the occurrence and development of type 2 diabetes and atherosclerosis.