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Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency with SLC25A13 Mutation Delivering Hepatic Steatosis and also Prolonged Jaundice. A hard-to-find Situation Report.
0, 1.4, 1.6, and 2.5, respectively; p for trend ＜0.01). Also, sdLDL-C was a sensitive marker for predicting the need for laser treatment among lipids (log rank, p=0.009), especially in patients with elderly (≧65 yrs) and obesity (BMI ≧25 kg/m
).

SdLDL-C is a sensitive target marker to predict cardiovascular events as well as the need for laser treatment in patients with hypercholesterolemia and diabetic retinopathy.
SdLDL-C is a sensitive target marker to predict cardiovascular events as well as the need for laser treatment in patients with hypercholesterolemia and diabetic retinopathy.Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by biallelic pathogenic mutations in the MTTP gene. Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver, resulting in malabsorption of fat and fat-soluble vitamins and severe hypolipidemia. Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy. The deficiency of fat-soluble vitamins progressively develops into a variety of symptoms later in life, including hematological (acanthocytosis, anemia, bleeding tendency, etc.), neuromuscular (spinocerebellar ataxia, peripheral neuropathy, myopathy, etc.), and ophthalmological symptoms (e.g., retinitis pigmentosa). If left untreated, the disease can be debilitating and even lethal by the third decade of life due to the development of severe complications, such as blindness, neuromyopathy, and respiratory failure. High dose vitamin supplementation is the mainstay for treatment and may prevent, delay, or alleviate the complications and improve the prognosis, enabling some patients to live to the eighth decade of life. However, it cannot fully prevent or restore impaired function. Novel therapeutic modalities that improve quality of life and prognosis are awaited. The aim of this review is to 1) summarize the pathogenesis, clinical signs and symptoms, diagnosis, and management of ABL, and 2) propose diagnostic criteria that define eligibility to receive financial support from the Japanese government for patients with ABL as a rare and intractable disease. In addition, our diagnostic criteria and the entry criterion of low-density lipoprotein cholesterol (LDL-C) ＜15 mg/dL and apoB ＜15 mg/dL can be useful in universal or opportunistic screening for the disease. Registry research on ABL is currently ongoing to better understand the disease burden and unmet needs of this life-threatening disease with few therapeutic options.
Familial hypercholesterolemia (FH) is underdiagnosed in most countries. The genetic heterogeneity of FH requires an algorithm to efficiently integrate genetic testing into clinical practice. We aimed to report the spectrum of genetic mutations from patients with clinically diagnosed FH in Taiwan.

Patients with LDL-C＞190 mg/dL or those with probable or definite FH according to the Taiwan Lipid Guidelines underwent genetic testing. Samples from 750 index patients from the Taiwan FH registry were screened using custom-made mass spectrometry, followed by targeted next generation sequencing (NGS) and/or multiplex ligation-dependent probe amplification (MLPA) if found negative.

The mean age of the patients was 52.4±15.1 years and 40.9% were male. Mutations were detected in 445 patients (59.3%). The distribution of mutations was as follows LDLR (n=395), APOB (n=58), PCSK9 (n=0), and ABCG5 (n=3). The most common mutations were APOB c.10579 C＞T (p.R3527W) (12.6%), LDLR c.986 G＞A (p.C329Y) (11.5%), and LDLR c.1747 C＞T (p.H583Y) (10.8%). LDLR c.1187-10 G＞A (IVS 8-10) and APOB c.10580 G＞A (p.R3527Q) were detected using targeted NGS in Taiwan for the first time. read more Four novel mutations were identified, including LDLR c.1060＋2 T＞C (IVS 7＋2), LDLR c.1139 A＞C (p.E380A), LDLR c.1322 T＞C (p.A431T)＋c.1867 A＞G (p.I623V), and ABCG5 c.1337 G＞A (p.R447Q).

LDLR and APOB, but not PCSK9, mutations were the major genetic causes of FH. Four novel mutations in LDLR or ABCG5 were identified. This genetic screening method using mass spectrometry, targeted NGS, and MLPA analysis provided an efficient algorithm for genetic testing for clinically diagnosed FH in Taiwan.
LDLR and APOB, but not PCSK9, mutations were the major genetic causes of FH. Four novel mutations in LDLR or ABCG5 were identified. This genetic screening method using mass spectrometry, targeted NGS, and MLPA analysis provided an efficient algorithm for genetic testing for clinically diagnosed FH in Taiwan.Anti-Müllerian hormone (AMH) is primarily produced by ovarian granulosa cells and contributes to follicle development. AMH is also produced in other tissues, including the brain and pituitary; however, its roles in these tissues are not well understood. In this study, we examined the effect of AMH on pituitary gonadotrophs. We detected AMH and AMH receptor type 2 expression in LβT2 cells. In these cells, the expression of FSHβ- but not α- and LHβ-subunits increased significantly as the concentration of AMH increased. LβT2 cells expressed Kiss-1 and Kiss-1R. AMH stimulation resulted in decreases in both Kiss-1 and Kiss-1R. The siRNA-mediated knockdown of Kiss-1 in LβT2 cells did not alter the basal expression levels of α-, LHβ-, and FSHβ-subunits. In LβT2 cells overexpressing Kiss-1R, exogenous kisspeptin stimulation significantly increased the expression of all three gonadotropin subunits. However, kisspeptin-induced increases in these subunits were almost completely eliminated in the presence of AMH. In contrast, GnRH-induced increases in the three gonadotropin subunits were not modulated by AMH. Our observations suggested that AMH acts on pituitary gonadotrophs and induces FSHβ-subunit expression with concomitant decreases in Kiss-1 and Kiss-1R gene expression. Kisspeptin, but not GnRH-induced gonadotropin subunit expression, was inhibited by AMH, suggesting that it functions in association with the kisspeptin/Kiss-1R system in gonadotrophs.The melanocortin-1 receptor gene (MC1R) controls production of the pigments eumelanin and pheomelanin. Changes in MC1R lead to variation in coat color in mammals, which can range from entirely black (melanism) to yellowish. In this study, we report a case of a wild-caught Norway rat (Rattus norvegicus) from Sado Island, Japan with a yellowish coat color. Upon sequencing the whole coding region of the Mc1r gene (954 bp), we found a 1-bp deletion at site 337 (c.337del), indicative of a frameshift mutation, which was characterized as a severe loss-of-function or null mutation. A spectrophotometer was used to measure coat color, revealing that the rat had a distinctly lighter coat, based on lightness score, than mice with homozygous similar loss-of-function mutations. This implies that loss-of-function mutations can yield different phenotypes in murine rodents. The loss-of-function-mutant rat exhibited a contrasting coat pattern consisting of darker and lighter colors along its dorsal and ventral sides, respectively.
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