BACKGROUND: Colorectal cancer in children and adolescents is an exceptional condition. Its clinical symptoms are non-specific, leading to delayed diagnosis and poor prognosis.
METHODS: The present article reports the case of a 15-year-old child followed for acute lymphoblastic leukemia with a history of a grandfather operated on and followed for colorectal cancer. The child was admitted to our department with an occlusive syndrome. Endoscopy and radiological findings suggested the diagnosis of colon adenocarcinoma (AC). The therapeutic decision was a segmental colectomy covering the right colonic angle and colostomy followed by chemotherapy.
CONCLUSIONS: Colorectal cancer remains an exceptional pathology in children. They often include abdominal pain, nausea, vomiting and rectal discharge. Endoscopy is the key diagnostic test, enabling both distal and proximal lesions to be detected. Primary CA of the colon is rare in children, and even rarer as a second malignancy.
CONCLUSIONS: The clinical symptoms of colorectal adenocarcinoma in children are non-specific. These cancers are little-known in pediatrics, and are often diagnosed at an advanced stage.

Recurring episodes of fever characterize tumor necrosis factor receptor-associated periodic syndrome (TRAPS) which is autosomal dominant. The primary symptoms of patients with TRAPS include prolonged fever, abdominal pain, muscle pain, and skin rashes. The prevalence of TRAPS appeared higher in Western countries than in Asian countries. Herein, we present the case of a 13-year-old girl who experienced intermittent fever for 8 years, with episodes that occur every 2 years. The patient demonstrated periodic fever, headache, vomiting, rash, and elevated inflammatory marker levels during the disease course. A heterozygous C55Y mutation was identified via a direct DNA sequencing of her genomic DNA. This mutation is located in exon 4 of TNFRSF1A. Genetic studies of her sister and mother revealed that they possessed the C55Y heterozygous mutation without demonstrating any clinical signs, while the father did not. Further, we conducted a thorough assessment of the literature and compiled the information from the eight TRAPS case series.

Hypoplastic left heart syndrome (HLHS) is a rare but genetically complex and clinically and anatomically severe form of congenital heart disease (CHD).
Here, we report on the use of rapid prenatal whole-exome sequencing for the prenatal diagnosis of a severe case of neonatal recurrent HLHS caused by heterozygous compound variants in the MYH6 gene inherited from the (healthy) parents. MYH6 is known to be highly polymorphic; a large number of rare and common variants have variable effects on protein levels. We postulated that two hypomorphic variants led to severe CHD when associated in trans; this was consistent with the autosomal recessive pattern of inheritance. In the literature, dominant transmission of MYH6-related CHD is more frequent and is probably linked to synergistic heterozygosity or the specific combination of a single, pathogenic variant with common MYH6 variants.
The present report illustrates the major contribution of whole-exome sequencing (WES) in the characterization of an unusually recurrent fetal disorder and considered the role of WES in the prenatal diagnosis of disorders that do not usually have a genetic etiology.

Familial longevity confers advantages in terms of health, functionality, and longevity. We sought to assess potential differences in frailty and sarcopenia in older adults according to a parental history of extraordinary longevity. A total of 176 community-dwelling subjects aged 65-80 years were recruited in this observational case-control study, pair-matched 1:1 for gender, age, and place of birth and residence: 88 centenarians\' offspring (case group) and 88 non-centenarians\' offspring (control group). The main variables were frailty and sarcopenia based on Fried\'s phenotype and the European Working Group on Sarcopenia in Older People (EWGSOP) definitions, respectively. Sociodemographics, comorbidities, clinical and functional variables, the presence of geriatric syndromes, and laboratory parameters were also collected. Related sample tests were applied, and conditional logistic regression was performed. Cases had a higher percentage of robust patients (31.8% vs. 15.9%), lower percentages of frailty (9.1% vs. 21.6%) and pre-frailty (59.1% vs. 62.5%) (p = 0.001), and lower levels of IL-6 (p = 0.044) than controls. The robust adjusted OR for cases was 3.00 (95% CI = 1.06-8.47, p = 0.038). No significant differences in muscle mass were found. Familial longevity was also associated with less obesity, insomnia, pain, and polypharmacy and a higher education level and total and low-density lipoprotein cholesterol. The results suggest an inherited genetic component in the frailty phenotype, while the sarcopenia association with familial longevity remains challenging.

BACKGROUND: Breast cancer is an umbrella term referring to a group of biologically and molecularly heterogeneous diseases originating from the breast. Globally, incidences of breast cancer has been increasing dramatically over the past decades. Analyses of multiple clinical \"big data\" can aid us in clarifying the means of preventing the disease. In addition, predisposing risk factors will be the most important issues if we can confirm their relevance. This study aims to provide an overview of the predisposing factors that contribute to a higher possibility of developing breast cancer and emphasize the signs that we ought to pay more attention to.
METHODS: This is a matched nested case-control study. The cohort focused on identifying the eligible risk factors in breast cancer development by data screening (2000-2013) from the Taiwan National Health Insurance Research Database (NHIRD) under approved protocol. A total of 486,069 females were enrolled from a nationwide sampled database, and 3281 females was elligible as breast cancer cohort, 478,574 females who had never diagnosed with breast cancer from 2000 to 2013 were eligible as non-breast cancer controls, and matched to breast cancer cases according to age using a 1:6 ratio.
RESULTS: We analyzed 3281 breast cancer cases and 19,686 non-breast cancer controls after an age-matched procedure. The significant predisposing factors associated with breast cancer development including obesity, hyperlipidemia, thyroid cancer and liver cancer. As for patients under the age of 55, gastric cancer does seem to have an impact on the development of breast cancer; compared with their counterparts over the age of 55, endometrial cancer appears to exhibit an evocative effect.
CONCLUSIONS: In this nationwide matched nested case-control study, we identified obesity, hyperlipidemia, previous cancers of the thyroid, stomach and liver as risk factors associated with breast cancer. However, the retrospective nature and limited case numbers of certain cancers still difficult to provide robust evidence. Further prospective studies are necessitated to corroborate this finding in order to nip the disease in the bud.
BACKGROUND: The studies involving human participants were reviewed and approved by the China Medical University Hospital [CMUH104-REC2-115(AR-4)].

The primary aim of this study was to determine if self-reported occupational noise exposure was associated with Raynaud\'s phenomenon. In northern Sweden, a nested case-control study was performed on subjects reporting Raynaud\'s phenomenon (N=461), and controls (N=763) matched by age, sex and geographical location. The response rate to the exposure questionnaire was 79.2%. The study showed no statistically significant association between occupational noise exposure and reporting Raynaud\'s phenomenon (OR 1.10; 95% CI 0.83-1.46) in simple analyses. However, there was a trend towards increasing OR for Raynaud\'s phenomenon with increasing noise exposure, although not statistically significant. Also, there was a significant association between noise exposure and hearing loss (OR 2.76; 95% CI 2.00-3.81), and hearing loss was associated with reporting Raynaud\'s phenomenon (OR 1.52; 95% CI 1.03-2.23) in a multiple regression model. In conclusion, self-reported occupational noise exposure was not statistically significantly associated with Raynaud\'s phenomenon, but there was a dose-effect trend. In addition, the multiple model showed a robust association between hearing loss and Raynaud\'s phenomenon. These findings offer some support for a common pathophysiological background for Raynaud\'s phenomenon and hearing loss among noise-exposed workers, possibly through noise-induced vasoconstriction.

UNASSIGNED: The incidence of breast cancer is growing rapidly worldwide (1.7 million new cases and 600,000 deaths per year). Moreover, about 10% of breast cancer cases occur in young women under the age of 45. The aim of the study was to report a rare case of BRCA 1-mutated breast cancer in a young patient with multiple affected relatives. Breast cancer is due to a genetic predisposition with BRCA1 and BRCA2 representing a significant proportion of families with a very high risk of developing the disease over a lifetime of up to 50-80%.
UNASSIGNED: In this paper we report a case of a 29-year-old woman with a confirmed diagnosis of left breast carcinoma.
UNASSIGNED: Mutations of the BRCA1 gene were revealed in the patient, in two of her sisters, brother and brother\'s daughter.

Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive (AR) immune disorder that has usually been associated to missense, nonsense or indels mutations in the LYST gene. In this study, we describe for the first time the case of a CHS patient carrying a homozygous mutation in the LYST gene inherited as a result of a partial uniparental isodisomy (UPiD) of maternal origin. Sanger sequencing of the LYST cDNA and single nucleotide polymorphism (SNP)-arrays were performed to identify the causative mutation and to explain the molecular mechanism of inheritance, respectively. Partial-UPiD leads to a copy neutral loss of heterozygosity (CN-LOH) of the telomeric region of chromosome 1 (1q41q44), unmasking the potential effect of the mutation detected. The mutation (c.8380dupT) is an insertion located in exon 32 of the LYST gene resulting in a premature stop codon and leading to the loss of all the conserved domains at the C-terminal of the LYST protein. This would account for the severe phenotype observed. We also reviewed the only two previously reported cases of CHS as a result of a uniparental disomy. In this study, we show that the combination of different strategies, including the use of SNP-arrays, is pivotal to fine-tune the diagnosis of rare AR disorders, such as CHS. Moreover, this case highlights the relevance of uniparental disomy as a potential mechanism of CHS expression in non-consanguineous families.

Recently, a novel syndrome of combined immune deficiency, infections, allergy, and inflammation has been attributed to mutations in the gene encoding actin-related protein 2/3 complex subunit 1B (ARPC1B), which is a key molecule driving the dynamics of the cytoskeleton. Homozygous mutations in the ARPC1B gene have been found to result in the disruption of the protein structure and cause an autosomal recessive syndrome of combined immune deficiency, impaired T-cell migration and proliferation, increased levels of immunoglobulin E (IgE) and immunoglobulin A (IgA), and thrombocytopenia. To date, only a few individuals have been diagnosed with the ARPC1B deficiency syndrome worldwide. In this case series, we report the wide spectrum of phenotype in 3 siblings of a consanguineous family from Afghanistan with a novel homozygous synonymous pathogenic variant c.783G>A, p. (Ala261Ala) of the ARPC1B gene that causes a similar syndrome but no thrombocytopenia. Targeted RNA studies demonstrated that the variant affects the splicing process of mRNA, resulting in a marked reduction of the levels of primary (normal) RNA transcript of the ARPC1B gene in the affected patients and likely premature termination from the abnormally spliced mRNA. The next generation sequencing (NGS) studies facilitated the diagnosis of this rare combined immunodeficiency and led to the decision to treat the affected patients with hematopoietic cell transplant (HCT) from an human leukocyte antigen (HLA)-matched healthy sibling.

Genetic mutations that result in loss-of-function of the protein A20 result in an early-onset autoinflammatory disease-haploinsufficiency of A20 (HA20). The reported clinical presentations of HA20 include a Behcet\'s disease-like phenotype and a more lupus-like phenotype. We have identified a novel mutation in the gene encoding A20 in a pediatric patient with chronic lymphadenopathy, lupus-like symptoms, and progressive hypogammaglobulinemia. This case illustrates the wide range of clinical symptoms, including immunodeficiency, that can occur in patients with HA20.