The role of genetics in Parkinson’s disease: a large cohort study in Chinese mainland population

This study aimed to determine the mutational spectrum of familial Parkinson’s disease and sporadic early-onset Parkinson’s disease (sEOPD) in a mainland Chinese population and the clinical features of mutation carriers. We performed multiplex ligation-dependent probe amplification assays and whole-exome sequencing for 1676 unrelated patients with Parkinson’s disease in a mainland Chinese population, including 192 probands from families with autosomal-recessive Parkinson’s disease, 242 probands from families with autosomal-dominant Parkinson’s disease, and 1242 sEOPD patients (age at onset ≤ 50). According to standards and guidelines from the American College of Medical Genetics and Genomics, pathogenic/likely pathogenic variants in 23 known Parkinson’s disease-associated genes occurred more frequently in the autosomal-recessive Parkinson’s disease cohort (65 of 192, 33.85%) than in the autosomal-dominant Parkinson’s disease cohort (10 of 242, 4.13%) and the sEOPD cohort (57 of 1242, 4.59%), which leads to an overall molecular diagnostic yield of 7.88% (132 of 1676). We found that PRKN was the most frequently mutated gene (n = 83, 4.95%) and present the first evidence of an SNCA duplication and LRRK2 p.N1437D variant in mainland China. In addition, several novel pathogenic/likely pathogenic variants including LRRK2 (p.V1447M and p.Y1645S), ATP13A2 (p.R735X and p.A819D), FBXO7 (p.G67E), LRP10 (c.322dupC/p.G109Rfs*51) and TMEM230 (c.429delT/p.P144Qfs*2) were identified in our cohort. Furthermore, the age at onset of the 132 probands with genetic diagnoses (median, 31.5 years) was about 14.5 years earlier than that of patients without molecular diagnoses (i.e. non-carriers, median 46.0 years). Specifically, the age at onset of Parkinson’s disease patients with pathogenic/likely pathogenic variants in ATP13A2, PLA2G6, PRKN, or PINK1 was significantly lower than that of non-carriers, while the age at onset of carriers with other gene pathogenic/likely pathogenic variants was similar to that of non-carriers. The clinical spectrum of Parkinson’s disease-associated gene carriers in this mainland Chinese population was similar to that of other populations. We also detected 61 probands with GBA possibly pathogenic variants (3.64%) and 59 probands with GBA p.L444P (3.52%). These results shed insight into the genetic spectrum and clinical manifestations of Parkinson’s disease in mainland China and expand the existing repertoire of pathogenic or likely pathogenic variants involved in known Parkinson’s disease-associated genes. Our data highlight the importance of genetic testing in Parkinson’s disease patients with age at onset < 40 years, especially in those from families with a recessive inheritance pattern, who may benefit from early diagnosis and treatment.

Maternal gestational diabetes mellitus and overweight and obesity in offspring: a study in Chinese children

The purpose of this study was to investigate the effects of maternal gestational diabetes mellitus (GDM) and breast feeding on childhood overweight and obesity in a mainland Chinese population. The incidence of and factors associated with overweight and obesity were compared between children of mothers with (n=1068) and without (n=1756) GDM. The independent roles of the associated factors were examined by multiple logistic regression analysis. The incidence of overweight was higher (16.6 v. 12.6%, P=0.002) in the GDM group, but that of obesity was not different (10.7 v. 12.0%, P=0.315). At age 1–2 and 2–5 years, no difference in overweight (11.0 v. 12.0%, P=0.917, and 15.7 v. 14.6%, P=0.693, respectively) was found, while obesity (8.0 v. 13.6%, P=0.019, and 8.4 v. 13.4%, P=0.014, respectively) was less frequent in the GDM offspring. At age 5–10 years, increased overweight (22.2 v. 12.1%, P<0.001) and obesity (15.9 v. 9.0%, P=0.001) were found in the GDM group, which was associated with maternal obesity, being born large-for-gestational age, male gender and formula feeding. After adjusting for confounding factors, GDM remained an independent determinant of offspring overweight and obesity (aOR 2.28, 95% CI 1.61–3.22), suggesting that the effects of GDM were independent of breast feeding, as well as of maternal obesity and birth size.

Adapting the Pyramids and Palm Trees Test and the Kissing and Dancing Test and developing other semantic tests for the Chinese population

ABSTRACTThe semantic system is a core component underlying many cognitive functions, and its deterioration can lead to various behavioral deficits. The Pyramids and Palm Trees Test (Howard & Patterson, 1992) and the Kissing and Dancing Test (Bak & Hodges, 2003) are among the most widely used semantic assessments, and they have been adapted into many languages and for many populations. We adapted these tests to the Mainland Chinese population by adopting culturally appropriate items and collecting normative data in healthy Chinese participants. In addition, accumulating research has shown that semantic representations have multidimensional structures that include various types of knowledge, and in the Pyramids and Palm Trees Test mainly evaluates associative relationships. Therefore, we developed additional tests to examine three other aspects of semantic knowledge: taxonomic, functional, and manipulative. We found significant correlations among all tests in healthy participants. Moreover, the level of education and age affected performance on the tests of associative relationships, taxonomic relationships, and manipulation similarity.