An Evaluation of the Protein Requirements of Japanese Young Men by Consuming Two Types of Dairy Proteins Using the Indicator Amino Acid Oxidation Method.

The indicator amino acid oxidation method is a relatively new method for determining protein requirements. Our hypothesis was that the protein requirement of the casein-whey protein mixture (70% casein and 30% whey protein) was lower than the protein requirement of plain casein, because casein and whey proteins compensate for the lack of the first-limiting amino acids. The optimal mixing ratio was determined based on the amino acid scoring pattern which is used to calculate the digestible indispensable amino acid score. In this study, digestibility was not considered to determine the optimal mixing ratio because dairy protein is a good source of digestible protein. This study aimed to evaluate the protein requirements of Japanese young men by consuming casein and casein-whey protein mixture. Ten healthy young men (22±0.2 y old) participated in 12 experiments according to a graded protein intake (0.5, 0.7, 0.9, 1.0, 1.2, 1.4 g/kg/d) of casein and casein-whey protein mixture. The mean protein requirement was calculated as the breakpoint of breath 13CO2 enrichment using change-point regression models. The mean protein requirements of Japanese young men by consuming casein and casein-whey protein mixture were estimated to be 1.00 g/kg/d and 0.90 g/kg/d, respectively. These estimated requirements were consistent with the protein quality expected from the amount of the first-limiting amino acids. The indicator amino acid oxidation method may be useful to evaluate protein quality.

Further delineation of auriculocondylar syndrome based on 14 novel cases and reassessment of 25 published cases.

Auriculocondylar syndrome (ACS) is a rare craniofacial disorder characterized by mandibular hypoplasia and an auricular defect at the junction between the lobe and helix, known as a "Question Mark Ear" (QME). Several additional features, originating from the first and second branchial arches and other tissues, have also been reported. ACS is genetically heterogeneous with autosomal dominant and recessive modes of inheritance. The mutations identified to date are presumed to dysregulate the endothelin 1 signaling pathway. Here we describe 14 novel cases and reassess 25 published cases of ACS through a questionnaire for systematic data collection. All patients harbor mutation(s) in PLCB4, GNAI3, or EDN1. This series of patients contributes to the characterization of additional features occasionally associated with ACS such as respiratory, costal, neurodevelopmental, and genital anomalies, and provides management and monitoring recommendations.

Divergent variant patterns among 19 patients with Rubinstein-Taybi syndrome uncovered by comprehensive genetic analysis including whole genome sequencing.

Rubinstein-Taybi syndrome (RSTS) is characterized by dysmorphic facial features, broad thumbs, and intellectual disability. CREB-binding protein (CREBBP) or E1A-binding protein P300 (EP300) are causative genes. To elucidate the underlying genetic and genomic architecture related to the RSTS phenotype, we performed comprehensive genetic analysis targeting CREBBP and/or EP300 in 22 clinically diagnosed patients. During the 11-year study period, we used several analysis methods including high-resolution melting, array-based comparative genomic hybridization, panel-based exome sequencing, whole exome sequencing, and whole genome sequencing (WGS). We identified the causative variants in 19 patients (86.3%), but they were variable and complex, so we must combine multiple analysis methods. Notably, we found genetic alterations in the non-coding regions of two patients (10.5%, 2/19): scattered deletions including a partial 5'-untranslated region of CREBBP in one patient (all coding exons were intact), and a deep 229-bp intronic deletion in another patient, resulting in a splicing error. Furthermore, we identified rare clinical findings: two patients with an EP300 variant showed abnormal development of the neural tube, and one patient with a CREBBP variant had anorectal atresia with a cloaca. Our findings expand the allelic heterogeneity of RSTS, underscore the utility of comprehensive genetic analysis, and suggest that WGS may be a practical diagnostic strategy.

Dietary cystine is important to maintain plasma mercaptalbumin levels in rats fed low-protein diets.

The oxidized/reduced state of plasma albumin in rats is influenced by the quantity of dietary protein. However, the effects of the protein quality on the oxidized/reduced state of plasma albumin are not clear. We hypothesized that the quality of dietary protein might modulate the oxidized/reduced state of plasma albumin. The aim of the present study was to examine whether the amino acid composition of dietary protein modulates the oxidized/reduced state of plasma albumin in rats. Male Sprague-Dawley rats were fed low-protein diets containing 5% casein (CA), 5% egg white (EW), or 6% wheat gluten (WG) for 2 weeks. The plasma albumin concentration gradually decreased in rats fed each diet; however, there was no significant difference among the groups. In rats fed the 5% CA diet, the percentage of mercaptalbumin within the total plasma albumin was significantly lower than in those fed the EW or WG diet. Compared with EW or WG, CA contains lower amounts of glycine and cystine. In rats fed a 5% CA diet supplemented with cystine, the percentage of mercaptalbumin was significantly higher than that in rats fed a 5% CA diet supplemented with glycine. The expression of hepatic eukaryotic initiation factor 4E-binding protein 1 was significantly lower in rats fed the cystine-supplemented diet than in those fed the glycine-supplemented diet. These results suggest that dietary protein with a high cystine content maintains plasma mercaptalbumin levels in rats fed low-protein diets.

Intake of Carbohydrate to Fiber Ratio Is a Useful Marker for Metabolic Syndrome in Patients with Type 2 Diabetes: A Cross-Sectional Study.

BACKGROUND/AIMS: The effect of low carbohydrate diet on human health is still controversial. Whole grain, which is carbohydrate rich in fiber, has protective effects on human health. Thus, we assumed that intake of carbohydrate to fiber ratio has an important role in human health. METHODS: This is a post-hoc analysis of a cross-sectional study of 164 patients with type 2 diabetes. Habitual food and nutrient intake were assessed and estimated by a self-administered diet history questionnaire. Intake of carbohydrate to fiber ratio was defined as carbohydrate (g)/fiber intake (g). Logistic regression analyses were performed to reveal the association between intake of carbohydrate to fiber ratio and metabolic syndrome (MetS). RESULTS: Intake of carbohydrate to fiber ratio has closely associated with metabolic parameters, including triglycerides (r = 0.21, p = 0.007) and high-density lipoprotein cholesterol (r = -0.23, p = 0.003). Intake of carbohydrate to fiber ratio was associated with MetS (OR 1.06 [95% CI 1.00-1.13], p = 0.047) after adjusting for covariates, whereas carbohydrate intake (1.00 [0.99-1.01], p = 0.752) or carbohydrate energy/total energy (1.00 [0.94-1.07], p = 0.962) was not associated with MetS. CONCLUSIONS: Intake of carbohydrate to fiber ratio was associated with MetS, whereas carbohydrate intake was not.

Urinary pH reflects dietary acid load in patients with type 2 diabetes.

Dietary acid load is important information, however, survey of food intake needs time and skill. Therefore, it is difficult to survey food intake from all patients. It remains to be elucidated the association between dietary acid load and urinary pH in patients with type 2 diabetes. In this cross-sectional study of 173 patients, we investigated the relationship between urinary pH and dietary acid load, assessed with potential renal acid load. Habitual food and nutrient intake was assessed by a self-administered diet history questionnaire. Urinary pH was negatively correlated with potential renal acid load (r = -0.24, p = 0.002). Multivariate regression analysis revealed that potential renal acid load (standardized regression coefficient = -0.21, p = 0.036) was associated with urinary pH after adjusting for covariates. In addition, according to the receiver operator characteristic analysis, the optimal cut-off point of urinary pH for high dietary acid load, defined as potential renal acid load over 7.0 mEq/day was 5.7 (area under the receiver operator characteristic curve 0.63 (95% CI 0.54-0.71), sensitivity = 0.56, specificity = 0.70, p = 0.004). Urinary pH was associated with dietary acid load in patients with type 2 diabetes. We suggest that urinary pH can be a practical screening marker for dietary acid load in patients with type 2 diabetes.

Current status of non-invasive prenatal testing in Japan.

AIM: The purpose of this study was to report the 3-year experience of a nationwide demonstration project to introduce non-invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the current status of NIPT in Japan. METHODS: Tests were conducted to detect aneuploidy in high-risk pregnant women, and adequate genetic counseling was provided. The clinical data, test results, and pregnancy outcomes were recorded. We discuss the problems of NIPT on the basis of published reports and meta-analyses. RESULTS: From April 2013 to March 2016, 30 613 tests were conducted at 55 medical sites participating in a multicenter clinical study. Among the 30 613 women tested, 554 were positive (1.81%) and 30 021 were negative (98.1%) for aneuploidy. Of the 289, 128, and 44 women who tested positive for trisomies 21, 18, and 13, respectively, and underwent definitive testing, 279 (96.5%), 106 (82.8%), and 28 (63.6%) were determined to have a true-positive result. For the 13 481 women with negative result and whose progress could be traced, two had a false-negative result (0.02%). The tests were performed on the condition that a standard level of genetic counseling be provided at hospitals. CONCLUSION: Here, we report on the 3-year nationwide experience with NIPT in Japan. It is important to establish a genetic counseling system to enable women to make informed decisions regarding prenatal testing. Moreover, a welfare system is warranted to support women who decide to give birth to and raise children with chromosomal diseases.

An oxidized/reduced state of plasma albumin reflects malnutrition due to an insufficient diet in rats.

We examined whether protein- and food-intake restrictions modulate the oxidized/reduced state of plasma albumin in Sprague-Dawley rats. Rats were fed a 3%, 5%, 10% or 20% casein diet for 2 weeks. The plasma albumin concentration significantly decreased with decreasing protein intake. However, no significant difference in plasma albumin concentration was seen between rats fed the 5% or 10% casein diet. In rats fed the 5% casein diet, the percentage of mercaptalbumin within total plasma albumin was significantly lower and that of nonmercaptalbumin-1 was significantly higher than in rats fed the 10% casein diet. In experiments with food-intake restriction for 2 weeks, rats were fed 50% or 75% of the amount of a 20% casein diet consumed by control rats. The percentage of mercaptalbumin was significantly lower and that of nonmercaptalbumin-2 was significantly higher in rats with food-intake restriction than in control rats. When rats with malnutrition were refed with the 20% casein diet ad libitum, the percentage of mercaptalbumin rapidly increased. The change in the percentage of mercaptalbumin was correlated with the plasma transthyretin concentration. These results indicate that the oxidized/reduced state of plasma albumin may be applied as a sensitive marker of nutritional status reflecting dietary pattern.

Comparisons of dietary intake in Japanese with non-alcoholic fatty liver disease and type 2 diabetes mellitus.

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease that involves a complex interaction between genetics, diet, and lifestyle, all of which combine to form the NAFLD phenotype. In Japan, medical nutrition therapy for NAFLD has not yet been established, so NAFLD patients are instructed in the dietary modifications used for type 2 diabetes mellitus (T2DM). Because points of difference may exist in the effects of dietary choices on NAFLD and T2DM, the present study aimed to compare and assess the dietary intake of Japanese individuals with NAFLD and T2DM. This cross-sectional study involved 219 patients (77 NAFLD subjects; 33 males, 44 females; 142 T2DM subjects: 76 males, 66 females) aged 40-79 years. Dietary intake was assessed using a validated self-administered diet history questionnaire. Among the results, the most notable in NAFLD patients relative to T2DM patients were: 1) the low intake of vegetables that can reduce the overall energy density; 2) the high consumption of fruits and confectionery containing simple carbohydrates such as fructose; and 3) BMI may be higher. We demonstrated differences in dietary selection between the two groups. NAFLD patients were more likely to have dietary habits that promote fat accumulation in the body.

The Issue of Nutrition in an Aging Society.

Viewed from a global perspective, Japan is often considered a country where the progression towards a low birthrate and longevity has been prominent. In 2007, the ratio of the aged population reached 21.5%, propelling Japan into the classification of a super aging society. The long-term care insurance system in Japan was initiated in the year 2000, as a general long-term care service system for the whole society, covering the nutrition, medical care, and welfare fields. The goal of nutrition in an aged society is the extension of healthy life expectancy. The ratio of elderly citizens with malnutrition is high. Due to the loss of teeth, and a decrease in digestive and physical functions, there is often a decrease in appetite, and the inability to obtain enough nutrition for physical homeostasis is related to such conditions as frailty and the partial loss of physical functions due to sarcopenia, as well as a decrease in the quality of life (QOL). The elderly can easily fall into a state of protein and energy malnutrition (PEM), due to a variety of causes. Accordingly, it is important to adopt an appropriate approach that ensures a correct understanding of the causes of malnutrition and the special characteristics of malnutrition in the elderly.

Differing phenotypes of Moyamoya disease in a familial case involving heterozygous c.14429G > A variant in RNF213.

Moyamoya disease (MMD) is a chronic steno-occlusive arteriopathy involving the development of abnormal collateral vessels. Ring finger protein (RNF213) on the 17q25.3 locus was identified as an MMD-susceptibility gene in East Asian populations. We report a 5-year-old Japanese boy diagnosed with cerebral infarction and unilateral MMD. Magnetic resonance angiography (MRA) showed severe stenosis of the left internal carotid artery (ICA), terminal portion of the left ICA, and left origin of the posterior cerebral artery. Genetic testing indicated a heterozygous c.14429G > A (formerly described as c.14576G > A) variant in RNF213. The boy's mother had no neurological symptoms, but sequencing of RNF213 showed the same variant, and MRA indicated stenosis of the terminal bilateral ICA. This is the first report, to our knowledge, of different MMD phenotypes in a familial case involving the same heterozygous c.14429G > A variant in RNF213. Genetic testing for RNF213 is suggested for family member screening.

Lower vegetable protein intake and higher dietary acid load associated with lower carbohydrate intake are risk factors for metabolic syndrome in patients with type 2 diabetes: Post-hoc analysis of a cross-sectional study.

AIMS/INTRODUCTION: A low-carbohydrate diet based on animal sources is associated with higher all-cause mortality, whereas a vegetable-based low-carbohydrate diet is associated with lower cardiovascular disease mortality. It has been suggested that acid/base imbalance might play an important role in some cardiometabolic abnormalities. The aims of the present study were to evaluate whether carbohydrate intake is associated with quality of dietary protein and acid load, and whether these are related to metabolic syndrome in patients with type 2 diabetes. MATERIALS AND METHODS: The present cross-sectional study involved 149 patients with type 2 diabetes. Dietary intake was assessed using a validated self-administered diet history questionnaire. Dietary acid load was assessed by potential renal acid load and net endogenous acid production. RESULTS: Mean daily total energy intake, carbohydrate intake, animal protein intake and vegetable protein intake were 1821.5 kcal, 248.8 g, 36.1 g and 31.1 g, respectively. Carbohydrate energy/total energy was negatively correlated with animal protein energy/total energy, potential renal acid load or net endogenous acid production score, and was positively correlated with vegetable protein energy/total energy. Logistic regression analyses showed that the subgroup of patients with a lower vegetable protein energy/total energy or higher potential renal acid load or net endogenous acid production score was significantly associated with the prevalence of metabolic syndrome. CONCLUSIONS: The present study showed that carbohydrate intake was associated with the quality of dietary protein and dietary acid load. Furthermore, decreased vegetable protein intake and increased dietary acid load were associated with the prevalence of metabolic syndrome.

A Simple Evaluation Method for the Quality of Dietary Protein in Rats Using an Indicator Amino Acid Oxidation Technique.

We demonstrated that the indicator amino acid oxidation (IAAO) method could be employed for the evaluation of quality of dietary protein by comparing the protein intakes required to meet metabolic demand in rats fed different proteins. The objective of this study was to validate a simple evaluation method for determining the quality of dietary protein using the IAAO technique. Male Sprague-Dawley rats (5-6 wk old) were fed meals composed of graded protein, using either casein, wheat gluten (WG), soy protein isolate (SPI), or egg white protein (EW), every 3 h from 09:00 to 18:00. Administration of L-[1-(13)C]phenylalanine was performed hourly from 15:00 to 18:00. The (13)CO2 level in breath CO2 was measured at 18:30. The protein intake values required to meet the metabolic demand based on the breath (13)CO2 data for the dietary casein, WG, SPI, and EW intake were 18.0, 22.2, 17.5, and 10.1 g/kg BW/d, respectively. The breath (13)CO2 concentrations corresponding to the protein intake of 7.5 g/kg BW/d for casein, WG, SPI, and EW were 9.8, 10.9, 10.3, and 8.9 (‰)/100 g BW, respectively. A significant correlation was demonstrated between the protein intake required to meet the metabolic demands and the (13)CO2 concentration in the breath for a protein intake of 7.5 g/kg BW/d (r=0.967; p<0.05). These results demonstrated that the protein intake required to meet metabolic demand could be estimated and that the quality of the dietary protein could be evaluated using the (13)CO2 concentration in the breath with a protein intake of 7.5 g/kg BW/d.

Additional patients with 4q deletion: Severe growth delay and polycystic kidney disease associated with 4q21q22 loss.

BACKGROUND: To the best of our knowledge, this is the third report concerning 4q21q22 deletions. In this report, we describe the cases of two girls with 4q deletion and polycystic kidney disease. G-banding confirmed the deletion in one patient but not in the other. METHODS: We describe the cases of two girls with 4q deletion and polycystic kidney disease. Chromosomal deletions were mapped to 4q21-22. One patient had a simple 4q contiguous gene deletion, whereas the other patient had a complicated chromosomal rearrangement. In patient 1, a smaller part of the 4q deletion was translocated to the 3p region. RESULTS: Fifty-four genes and 72 genes were deleted in patients 1 and 2, respectively. In both patients, 52 genes were consistently deleted. CONCLUSION: The present two patients had a similar phenotype, including severe growth and developmental retardation, and a characteristic facial appearance. The loss of RPKG2 and RASGEF1B causes severe growth defect. PKD2 loss causes kidney cysts.

Egg Yolk Protein Delays Recovery while Ovalbumin Is Useful in Recovery from Iron Deficiency Anemia.

Protein is a main nutrient involved in overall iron metabolism in vivo. In order to assess the prevention of iron deficiency anemia (IDA) by diet, it is necessary to confirm the influence of dietary protein, which coexists with iron, on iron bioavailability. We investigated the usefulness of the egg structural protein in recovery from IDA. Thirty-one female Sprague-Dawley rats were divided into a control group (n = 6) fed a casein diet (4.0 mg Fe/100 g) for 42 days and an IDA model group (n = 25) created by feeding a low-iron casein diet (LI, 0.4 mg Fe/100 g) for 21 days and these IDA rats were fed normal iron diet with different proteins from eggs for another 21 days. The IDA rats were further divided into four subgroups depending on the proteins fed during the last 21 days, which were those with an egg white diet (LI-W, 4.0 mg Fe/100 g, n = 6), those with an ovalbumin diet (LI-A, 4.0 mg Fe/100 g, n = 7), those with an egg yolk-supplemented diet (LI-Y, 4.0 mg Fe/100 g, n = 6), and the rest with a casein diet (LI-C, 4.0 mg Fe/100 g, n = 6). In the LI-Y group, recovery of the hematocrit, hemoglobin, transferrin saturation level and the hepatic iron content were delayed compared to the other groups (p < 0.01, 0.01, 0.01, and 0.05, respectively), resulting in no recovery from IDA at the end of the experimental period. There were no significant differences in blood parameters in the LI-W and LI-A groups compared to the control group. The hepatic iron content of the LI-W and LI-A groups was higher than that of the LI-C group (p < 0.05). We found that egg white protein was useful for recovery from IDA and one of the efficacious components was ovalbumin, while egg yolk protein delayed recovery of IDA. This study demonstrates, therefore, that bioavailability of dietary iron varies depending on the source of dietary protein.

Breakpoint analysis of the recurrent constitutional t(8;22)(q24.13;q11.21) translocation.

BACKGROUNDS: The t(8;22)(q24.13;q11.2) has been identified as one of several recurrent constitutional translocations mediated by palindromic AT-rich repeats (PATRRs). Although the breakage on 22q11 utilizes the same PATRR as that of the more prevalent constitutional t(11;22)(q23;q11.2), the breakpoint region on 8q24 has not been elucidated in detail since the analysis of palindromic sequence is technically challenging. RESULTS: In this study, the entire 8q24 breakpoint region has been resolved by next generation sequencing. Eight polymorphic alleles were identified and compared with the junction sequences of previous and two recently identified t(8;22) cases . All of the breakpoints were found to be within the PATRRs on chromosomes 8 and 22 (PATRR8 and PATRR22), but the locations were different among cases at the level of nucleotide resolution. The translocations were always found to arise on symmetric PATRR8 alleles with breakpoints at the center of symmetry. The translocation junction is often accompanied by symmetric deletions at the center of both PATRRs. Rejoining occurs with minimal homology between the translocation partners. Remarkably, comparison of der (8) to der(22) sequences shows identical breakpoint junctions between them, which likely represent products of two independent events on the basis of a classical model. CONCLUSIONS: Our data suggest the hypothesis that interactions between the two PATRRs prior to the translocation event might trigger illegitimate recombination resulting in the recurrent palindrome-mediated translocation.

Type 2 diabetic conditions in Otsuka Long-Evans Tokushima Fatty rats are ameliorated by 5-aminolevulinic acid.

A precursor of protoporphyrin IX, 5-aminolevulinic acid (5-ALA) is used as a prodrug for photodiagnosis and photodynamic therapy. Recently, it has been shown that 5-ALA reduces glucose levels during fasting and after glucose loading in prediabetic subjects. We hypothesized that 5-ALA ameliorates diabetic conditions through mitochondrial changes in visceral adipose tissue. In order to explore the metabolic effects on the type 2 diabetic state, we administered ALA hydrochloride in combination with sodium ferrous citrate to Otsuka Long-Evans Tokushima Fatty (OLETF) rats at intragastric doses of 20 and 300 mg kg(-1) d(-1) for 6 weeks. The administration of 300 mg kg(-1) d(-1) of 5-ALA improved glucose intolerance, hypertriglyceridemia, and hyperleptinemia in OLETF rats more effectively than the administration of an equivalent dose of metformin, in accordance with reductions in food intake and body weight. Furthermore, the weight of the retroperitoneal fat tended to decrease and cellular mitochondrial content of the fat was markedly reduced by the 5-ALA administration, showing a positive correlation. These results suggest that 5-ALA ameliorates diabetic abnormalities in OLETF rats by reducing the visceral fat mass and mitochondrial content of adipocytes in a site-specific manner.

QOL in caregivers of Japanese patients with Prader-Willi syndrome with reference to age and genotype.

This study aimed to measure quality of life (QOL) of the primary family caregivers for patients with Prader-Willi syndrome (PWS). Comparisons were made between caregivers' QOL in regard to their dependents' genotype and age group. The participants with PWS consisted of 22 children (aged from 6 to 12 years) and 23 adolescents (aged from 13 to 19 years), including 6 children and 7 adolescents with maternal uniparental disomy (mUPD) and 16 children and 16 adolescents with deletion (DEL). The QOL of the primary family caregiver for each patient was assessed using the Japanese version of the WHOQOL-BREF. To examine the effect that age (children vs. adolescents) and genotype (DEL vs. mUPD) have on the QOL of caregivers, a two-way ANOVA was conducted, followed by the Bonferroni procedure to test the simple main effects. The two age groups and the two genotypes of PWS were used as independent variables and the total QOL of caregivers as a dependent variable. The two-way ANOVA (F(1, 41) = 6.98, P < 0.05), followed by the Bonferroni procedure, showed the following: the total QOL of caregivers of DEL adolescents showed little difference from that with DEL children, but the QOL of caregivers for mUPD adolescents was shown to be lower than that with mUPD children along with that of caregivers with DEL adolescents. There is hence a growing tendency for the deterioration in the QOL of caregivers to manifest itself later in the patients' adolescence, found mainly with mUPD patients.

Autism spectrum disorders and hyperactive/impulsive behaviors in Japanese patients with Prader-Willi syndrome: a comparison between maternal uniparental disomy and deletion cases.

This study aims to compare maternal uniparental disomy 15 (mUPD) and a paternal deletion of 15q11-13 (DEL) of Prader-Willi syndrome (PWS) in regard to autism spectrum disorders (ASD). Forty-five Japanese individuals with PWS were recruited from a single recruitment center. The participants consisted of 22 children (aged from 6 to 12) and 23 adolescents (aged from 13 to 19). Six children and seven adolescents were confirmed as having mUPD. Sixteen children and 16 adolescents were confirmed as having DEL. Under blindness to the participants' genotypes, a single psychologist carried out behavioral and psychological assessments, including the Wechsler Intelligence Scales, Pervasive Developmental Disorders Autism Society Japan Rating Scale (PARS), and ADHD-Rating Scale-IV (ADHD-RS-IV). Two comparisons were made: one between mUPD and DEL children and another between mUPD and DEL adolescents. In children, no significant differences were found between mUPD and DEL participants in terms of autistic (PARS childhood, P = 0.657) and impulsive behaviors (ADHD-RS-IV hyperactive/impulsive, P = 0.275). In adolescents, mUPD patients showed significantly more autistic symptomatology (PARS adolescent, P = 0.027) and significantly more impulsive behavior (ADHD-RS-IV hyperactive/impulsive, P = 0.01) than DEL patients. Our findings about Japanese PWS patients were consistent with previous researches from western countries not focused on Asian patients, indicating that mUPD cases would be more prone to ASD than DEL cases, regardless of ethnoregional differences. In addition, our data suggested that the behavioral difference between mUPD and DEL cases in terms of autistic and impulsive symptoms tend to be unrecognizable in their childhood.