Whole-genome sequencing revealed a novel long-range deletion mutation spanning GNAS in familial pseudohypoparathyroidism.

BACKGROUND: Pseudohypoparathyroidism (PHP) is a series of diseases related to pathological changes and neurocognitive and endocrine abnormalities, mainly due to the GNAS mutation on chromosome 20q13.2, which weakens receptor-mediated hormone signal transduction. Considering its complex genetic and epigenetic characteristics, GNAS may produce complex clinical phenotypes in families or sporadic cases. This study presented a case of familial PHP caused by a deletion mutation in the 20q13.2 region. METHODS AND RESULTS: The proband and her second daughter had PHP, and the proband's mother had pseudo-PHP. Whole-genome sequencing revealed that the proband had an 849.81 kb deletion spanning GNAS near the maternal 20q13.2 chromosome. Multiplex ligation-dependent probe amplification methylation analysis indicated that the proband as well as her mother and second daughter had seemingly abnormal GNAS methylation. This is different from the phenotype (feeding difficulty, slow growth, and special facial features) of previously reported cases with the deletion of fragments near the 20q13.2 chromosome. CONCLUSIONS: This report demonstrated the variability of 20q13.2 deletion phenotypes and the clinical importance of using multiple molecular genetic detection methods.

[Study on Relationship Between Serum 25-hydroxyvitamin D3 Concentration and Glucose Metabolism].

OBJECTIVES: To investigate the relationship between serum 25-hydroxyvitamin D3 [25(OH)D3 ] concentration and glucose metabolism. METHODS: This cross-sectional survey recruited 668 participants, and the demographic and clinical characteristics of the participants were obtained from questionnaires. Physical examination and blood biochemical examination were performed, then the participants were divided into three groups as normal glucose tolerant (NGT) group, impaired glucose regulation(IGR) group, and diabetes mellitus (DM) group. RESULTS: There was no statistical significant difference in serum 25(OH)D3 concentration among the three groups ( P>0.05). With comparison of different serum 25(OH) D3 concentration, there was no statistical significant difference in the incidence of DM and IGR, FPG, 2 h BG, HOMA-IR, ISI-composite, HOMA-ß or ΔI30/ΔG30 ( P>0.05). Serum 25(OH)D3 concentration was not associated with DM, IGR, FPG, 2 h BG, HOMA-IR, ISI-composite, HOMA-ß or ΔI30/ΔG30 ( P>0.05). CONCLUSIONS: No relationship between serum 25(OH)D3 concentration and glucose metabolism is comfirmed.

[Incidence and risk factors of amputation among inpatients with diabetic foot].

OBJECTIVE: To evaluate the incidence and risk factors of lower extremity amputation among inpatients with diabetic foot. METHODS: For this retrospective study, a total of 685 inpatients with diabetic foot (Wagner grade 1-5) admitted at a multi-disciplinary Diabetic Foot Care Center, West China Hospital, Sichuan University during January 1, 2005 and June 30, 2011. The data of each patient including clinical information, laboratory results and final outcome were collected and analyzed. They were divided into non-amputated and amputated groups. And the latter included minor and major amputation groups according to amputation site. RESULTS: The overall amputation rate was 11.4% in diabetic foot inpatients. The incidences of minor amputation and major amputation were 5.4% and 6.0% respectively. 17.9% of amputated patients experienced a second amputation. The amputated patients had a longer hospitalized stay, higher counts of white blood cells and neutrophils, greater HbA1c and lower serum levels of hemoglobin and albumin than the non-amputation patients (P < 0.05). The prevalence of diabetic peripheral neuropathy was significantly higher in the amputation group than that in the non-amputation group (P < 0.05). However, no difference existed between the minor and major amputation groups (P > 0.05). Ankle brachial index (ABI) in the amputation group was significantly lower than that in the non-amputation group (0.41 ± 0.25 vs 0.91 ± 0.36, P < 0.01). Minor and major amputation inpatients had similar ABI (0.43 ± 0.24 vs 0.39 ± 0.26, P = 0.087). Ordinal regression showed that HbA1c (P = 0.015), ABI (P = 0.016), history of amputation (P < 0.01) and Wagner grade of diabetic foot (P < 0.01) were the independent risk factors of amputation. CONCLUSIONS: Diabetic foot inpatients have a higher rate of lower extremity amputation. The risk factors of amputation include HbA1c, ABI, history of amputation and Wagner grade of diabetic foot. And diabetic peripheral neuropathy, ischemia of lower limbs (especially peripheral arterial diseases below knees), infection and nutritional state are closely associated with amputation of diabetic foot inpatients.

[Comparison of different diagnostic criteria for metabolic syndrome in Sichuan population].

OBJECTIVE: To evaluate the consistency of the diagnostic criteria for metabolic syndrome (MS) proposed by World Health Organization 1999 (WHO1999), National Cholesterol Education Program Adult Treatment Panel III 2005 (ATP III 2005), Chinese Diabetes Society 2004 (CDS2004), and International Diabetes Federation 2005 (IDF2005), and to identify a more applicable one for people in Sichuan. METHODS: A cross-sectional survey on MS was conducted in Sichuan. A total of 3511 participants were recruited through multistage cluster random sampling. A questionnaire was administered to the participants, along with physical examinations and laboratory tests involving oral glucose tolerance test and lipid profiles. The MS patients were identified by the above-mentioned diagnostic criteria. RESULTS: According to the ATP III (2005), the prevalence and age-adjusted prevalence of MS were 22.4% and 19.8% in Sichuan population respectively, significantly higher than those identified by the other 3 diagnostic criteria. The prevalence of MS increased with age. Men had higher prevalence of MS than women (P < 0.05) according to the CDS (2004) and WHO (1999). But women had higher prevalence of MS than men according to the IDF (2005) and no gender difference in the prevalence of MS existed according to the ATP III (2005). No significant difference was found in the prevalence of MS between the Han ethnicity and the Yi ethnicity regardless which diagnostic criteria were adopted. The 4 MS diagnostic criteria reached a consistency of 81.17%. The highest consistency (95.70%) occurred between the IDF (2005) and the ATP III (2005), with a kappa coefficient of 0.867 (P = 0.000). Significantly higher morbidity of myocardial infarction (MI) and/or cerebral stroke was found in MS patients regardless which criteria applied. The morbidity of MI and cerebral stroke in MS patients identified by the 4 criteria showed no difference (P = 0.556). CONCLUSION: ATP III (2005) has stricter criteria for MS than the others. The prevalence of MS increases with age. There is no significant difference in the prevalence of MS between the Han and Yi ethnicities. In Sichuan, the CDS (2004) is more applicable than the others.