Introduction: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical features of retinal dystrophy, obesity, postaxial polydactyly, renal anomalies, learning disabilities, hypogonadism, and genitourinary abnormalities. Nevertheless, previous studies on the phenotypic traits of BBS heterozygous carriers have generated inconclusive results. The aim of our study was to investigate the impact of BBS heterozygosity on carriers when compared to non-carriers within the Taiwanese population. Materials and Methods: This study follows a hospital-based case-control design. We employed the Taiwan Biobank version 2 (TWBv2) array to identify three specific loci associated with BBS (rs773862084, rs567573386, and rs199910690). In total, 716 patients were included in the case group, and they were compared to a control group of 2,864 patients who lacked BBS alleles. The control group was selected through gender and age matching at a ratio of 1:4. The association between BBS-related loci and comorbidity was assessed using logistic regression models. Results: We found that BBS heterozygous carriers exhibited a significant association with elevated BMI levels, especially the variant rs199910690 in MKS1 (p=0.0037). The prevalence of comorbidities in the carriers\' group was not higher than that in the non-carriers\' group. Besides, the average values of the biochemistry data showed no significant differences, except for creatinine level. Furthermore, we conducted a BMI-based analysis to identify specific risk factors for chronic kidney disease (CKD). Our findings revealed that individuals carrying the CA/AA genotype of the BBS2 rs773862084 variant or the CT/TT genotype of the MKS1 rs199910690 variant showed a reduced risk of developing CKD, irrespective of their BMI levels. When stratified by BMI level, obese males with the MKS1 rs199910690 variant and obese females with the BBS2 rs773862084 variant exhibited a negative association with CKD development. Conclusion: We found that aside from the association with overweight and obesity, heterozygous BBS mutations did not appear to increase the predisposition of individuals to comorbidities and metabolic diseases. To gain a more comprehensive understanding of the genetic susceptibility associated with Bardet-Biedl Syndrome (BBS), further research is warranted.

UNASSIGNED: Various genes have been associated with familial and sporadic primary hyperparathyroidism (PHPT), including activating mutations of the glial cells missing transcription factor 2 (GCM2) gene.
UNASSIGNED: The aim of this study was to assess the prevalence of the GCM2 p.Tyr394Ser variant in the Jerusalem Ashkenazi Jewish (AJ) population with PHPT, and to conclude whether routine genetic testing is justified.
UNASSIGNED: The blood of 40 self-reported AJ patients with PHPT and 200 AJ controls was tested for the GCM2 p.Tyr394Ser variant. Demographic and medical information was extracted from the patients\' charts and evaluated accordingly.
UNASSIGNED: Two (5%) PHPT patients and 3 (1.5%) controls were heterozygotes for the tested variant. Our patients were mostly (87.5%) sporadic cases. One of the heterozygote patients had familial PHPT; the other had 2 parathyroid adenomas, and the levels of his blood and urinary calcium were extremely high.
UNASSIGNED: Our results suggest that in AJ patients with sporadic, single-gland PHPT, the likelihood of the tested variant is low and genetic testing should be limited to those with familial PHPT or multiglandular disease.

Robertsonian translocation is the most common chromosomal rearrangement in mammals, and represents the type of chromosomal change that most effectively contributes to speciation in natural populations. Rb translocations involve double-strand DNA breaks at the centromere level in two telocentric chromosomes, followed by repair ligation of the respective long arms, creating a metacentric Rb chromosome. Many different chromosomal races have been described in Mus musculus domesticus that show reduced chromosome numbers due to the presence of Rb metacentric chromosomes. The crossroads between ancestral telocentrics and the new metacentric chromosomes should be resolved in the meiotic cells of the heterozygote individuals, which form trivalents. The preferential segregation of metacentric chromosomes to the egg during female meiosis I has been proposed to favor their fixation and eventual conversion of a telocentric karyotype to a metacentric karyotype. This biased segregation, a form of meiotic drive, explains the karyotype changes in mammalian species that have accumulated Rb fusions. We studied and compared the number of Rb chromosomes inherited by the offspring of multiple Rb heterozygous of M. domesticus in reciprocal crosses. We did not find that the Rb chromosomes were inherited preferentially with respect to the telocentric chromosomes; therefore, we found no evidence for the meiotic drive, nor was there a random distribution of Rb chromosomes inherited by the descendants.

We screened 62 late-onset ataxia patients for the AAGGG pathological expansion in the RFC-1 gene that, when biallelic, causes Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS). Nine patients tested positive. Six had a previous diagnosis of sporadic adult-onset ataxia (SAOA) and three of multisystem atrophy type C (MSA-C). Further six patients were heterozygous for the pathological RFC-1 expansion, four with an initial diagnosis of MSA-C and two of SAOA. In comparison with CANVAS, MSA-C patients had faster progression and shorter disease duration to walking with aids. An abnormal DaTscan does not seem to contribute to differential diagnosis between CANVAS and MSA-C.

Fanconi anemia (FA) is a cancer-prone inherited bone marrow failure syndrome caused by biallelic pathogenic variants in one of >22 genes in the FA/BRCA DNA repair pathway. A major concern is whether the risk of cancer is increased in individuals with a single pathogenic FA gene variant.
We evaluated the risk of cancer in the relatives of patients with FA in the National Cancer Institute Inherited Bone Marrow Failure Syndrome cohort. We genotyped all available relatives and determined the rates, types of cancer and the age of patients at cancer diagnosis. We calculated the observed-to-expected (O/E) cancer ratios using data from the Surveillance, Epidemiology, and End Results Program adjusted for age, sex, and birth cohort.
The risk of cancer was not increased among all FA relatives and FA heterozygotes (O/E ratios of 0.78 and 0.79, respectively). In particular, the risk of cancer was not increased among FANCA or FANCC heterozygotes (O/E ratios of 0.92 and 0.71, respectively). Relatives did not have typical FA cancers, and age at cancer diagnosis was not younger than expected.
Understanding the risk of cancer in individuals with single pathogenic FA variants is critical for counseling and management. We did not find increased risk of cancer in these individuals. These findings do not extend to the known cancer predisposition autosomal dominant FA genes, namely BRCA1, BRCA2, PALB2, BRIP1, and RAD51C.

The proliferation of genetic profiling has revealed many associations between genetic variations and disease. However, large-scale phenotyping efforts in largely healthy populations, coupled with DNA sequencing, suggest variants currently annotated as pathogenic are more common in healthy populations than previously thought. In addition, novel and rare variants are frequently observed in genes associated with disease both in healthy individuals and those under suspicion of disease. This raises the question of whether these variants can be useful predictors of disease. To answer this question, we assessed the degree to which the presence of a variant in the cardiac potassium channel gene KCNH2 was diagnostically predictive for the autosomal dominant long QT syndrome.
We estimated the probability of a long QT diagnosis given the presence of each KCNH2 variant using Bayesian methods that incorporated variant features such as changes in variant function, protein structure, and in silico predictions. We call this estimate the posttest probability of disease. Our method was applied to over 4000 individuals heterozygous for 871 missense or in-frame insertion/deletion variants in KCNH2 and validated against a separate international cohort of 933 individuals heterozygous for 266 missense or in-frame insertion/deletion variants.
Our method was well-calibrated for the observed fraction of heterozygotes diagnosed with long QT syndrome. Heuristically, we found that the innate diagnostic information one learns about a variant from 3-dimensional variant location, in vitro functional data, and in silico predictors is equivalent to the diagnostic information one learns about that same variant by clinically phenotyping 10 heterozygotes. Most importantly, these data can be obtained in the absence of any clinical observations.
We show how variant-specific features can inform a prior probability of disease for rare variants even in the absence of clinically phenotyped heterozygotes.

Hereditary persistence of fetal hemoglobin (HPFH) is a benign condition in which significant fetal hemoglobin production continues well into adulthood, disregarding the normal shutoff point after which only adult-type hemoglobin should be produced. The percentage of incorrect expression might be as low as 10%-15% or as high as 100% of the total hemoglobin, usually higher in homozygotes than in heterozygotes. The present case is a typical example of homozygous HPFH.

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The aims of this review were to understand the roles of bitter taste genes in humans. Some of the peoples have the capacity to taste some chemical substance such as phenylthiocarbamide (PTC) while others cant not based on the dietary hazards and food preferences. There are two alleles responsible to express these phenotypes which are homozygous recessive. In human TAS2R38 genes located on the chromosome number 7 and consist of different nucleotide polymorphism that related to detection of the phenotype of different chemical compounds such as 6-n-propylthiouracil (PROP) and phenylthiocarbamide bitterness and this Gene is the member of the TAS2R genes which are eleven pseudogenes and twenty that has roles in many biological processes. There are many factors that affect the bitter taste such as food, age, sex, and different diseases. The mechanism of food bitter taste and genotype of TAS2R38 until know not well understood due to that the proof of relation between bitter taste sensitivity and food is harmful. there are many different diseases can impact the influence of taste such as neoplasm and lifestyle such as consumption of alcohol along with the use of medication, head trauma, upper tract infections. On the other hand, A relation between TAS2R38 genotype and meal preferences has been observed among children, however, no associations have been mentioned among older adults. Some previous research proved some vital points that show an association between type 1 of diabetes and phenylthiocarbamide (PTC) but other studies cannot demonstrate that. However, of other disease such as obesity is controversial but other studies reported to the relationship between them.

Heterozygous mutations in the glucocerebrosidase gene (GBA) have been shown to be an important genetic risk factor for Parkinson\'s disease (PD) worldwide. However, the penetrance of GBA heterozygote for L444P, the common mutation for Asian population, is not known in older Chinese people.
To assess the conversion rate to PD in identified carriers of GBA L444P/R mutations in Chinese community-dwelling older adults.
The GBA gene was sequenced for mutations at position 444 in 8405 people older than 55 years who participated in the Beijing Longitudinal Study on Aging II cohort. Nine subjects were identified as heterozygous carriers of GBA L444P or L444R mutations at baseline and clinically followed up from 2009 to 2019 to investigate their PD conversion, motor and nonmotor symptoms, and change of vesicular monoamine transporter type 2 using tracer of [18 F]9-fluoropropyl-(+)-dihydrotetrabenazine (18 F-DTBZ, also known as 18 F-AV-133).
Eight heterozygous GBA L444P and 1 L444R mutation carriers were identified without PD at baseline, and none of them developed clinical parkinsonism after a 10-year follow-up.
Although GBA mutations may lead to an earlier onset PD, the majority of GBA L444P heterozygotes in older adults may not convert to PD. Further studies are warranted to identify factors that modify the risk of conversion. © 2020 International Parkinson and Movement Disorder Society.