Juarezmeyers6506

MRI of the brain showed severe cerebellar hypoplasia. Patient 4 (c.971A>G, p.Glu324Gly), a 14-year-old boy, presented on day 1 of life with tremor, hypotonia, dystonia, nystagmus, facial dysmorphism, and later seizures. MRI of the brain revealed moderate cerebellar hypoplasia.

D-DEMØ represents an

-related phenotype, the observation of which should trigger investigation for

mutations. Our findings, and the presence of multiple distinct

-related phenotypes, support the possibility that there are differences in the underlying mechanisms.

D-DEMØ represents an ATP1A3-related phenotype, the observation of which should trigger investigation for ATP1A3 mutations. Our findings, and the presence of multiple distinct ATP1A3-related phenotypes, support the possibility that there are differences in the underlying mechanisms.

To define the phenotypic spectrum of isolated sulfite oxidase (ISOD) and molybdenum cofactor deficiency (MoCD), aiming to promote timely diagnosis and assist in future clinical trial design.

We analyzed clinical, radiographic, biochemical, and genetic data from 146 patients reported in the literature.

We stratified patients into 2 phenotypic subgroups based on clinical and radiographic characteristics. In the first (Class I), patients presented early in life (age 1-50 days) with acute onset of neurologic symptoms and development of diffuse brain injury with cystic leukomalacia. Patients in the second subgroup (Class II) presented later in life (age 30 days-23 years) with prominent movement abnormalities and selective injury of the basal ganglia and cerebellum. A significant difference in survival estimates correlated with milder disease severity among Class II patients. Substantial overlap in sulfur-containing metabolite levels prevented discrimination of subgroups based on diagnostic biomarkers, but genotype-phenotype correlations suggested that residual SUOX activity may contribute to milder phenotypes.

Patients with SUOX and MoCD gravitate toward 1 of 2 distinct clinicoradiographic profiles. Patient stratification may help promote accurate diagnosis, prognostication, and aid in the design of future clinical trials.

Patients with SUOX and MoCD gravitate toward 1 of 2 distinct clinicoradiographic profiles. Patient stratification may help promote accurate diagnosis, prognostication, and aid in the design of future clinical trials.

We aimed to determine whether 3D imaging reconstruction allows identifying molecularclinical associations in myotonic dystrophy type 1 (DM1).

We obtained myoblasts from 6 patients with DM1 and 6 controls. We measured cytosine-thymine-guanine (CTG) expansion and detected RNA foci and muscleblind like 1 (MBNL1) through 3D reconstruction. We studied dystrophia myotonica protein kinase (DMPK) expression and splicing alterations of MBNL1, insulin receptor, and sarcoplasmic reticulum Ca(2+)-ATPase 1.

Three-dimensional analysis showed that RNA foci (nuclear and/or cytoplasmic) were present in 45%-100% of DM1-derived myoblasts we studied (range 0-6 foci per cell). RNA foci represented <0.6% of the total myoblast nuclear volume. CTG expansion size was associated with the number of RNA foci per myoblast (

= 0.876 [95% confidence interval 0.222-0.986]) as well as with the number of cytoplasmic RNA foci (

= 0.943 [0.559-0.994]). Although MBNL1 colocalized with RNA foci in all DM1 myoblast cell lines, colocalization only accounted for 1% of total MBNL1 expression, with the absence of DM1 alternative splicing patterns. The number of RNA foci was associated with DMPK expression (

= 0.967 [0.079-0.999]). On the other hand, the number of cytoplasmic RNA foci was correlated with the age at disease onset (

= -0.818 [-0.979 to 0.019]).

CTG expansion size modulates RNA foci number in myoblasts derived from patients with DM1. MBNL1 sequestration plays only a minor role in the pathobiology of the disease in these cells. Higher number of cytoplasmic RNA foci is related to an early onset of the disease, a finding that should be corroborated in future studies.

CTG expansion size modulates RNA foci number in myoblasts derived from patients with DM1. MBNL1 sequestration plays only a minor role in the pathobiology of the disease in these cells. Higher number of cytoplasmic RNA foci is related to an early onset of the disease, a finding that should be corroborated in future studies.

To report a neuroradiologic phenotype associated with reduced generation of multiple motile cilia (RGMC) and mutations in the

gene. We hypothesize that the observed phenotype may reflect the emerging role that ependymal cilia play in regulating CSF production.

Clinical and radiologic records were retrospectively reviewed for 7 consecutive patients diagnosed by the Leicester UK national primary ciliary dyskinesia (PCD) diagnostic laboratory.

On MRI scanning, all patients demonstrated hydrocephalus, choroid plexus hyperplasia (CPH), and arachnoid cysts. No patient had any sign of neurologic deficit. All patients had significant lung disease.

We conclude that there is a high incidence of hydrocephalus, arachnoid cysts, and CPH in

-associated RGMC. In all cases, the observed hydrocephalus seems arrested in childhood without progression or adverse neurologic sequelae. Our new observation of CPH, which is associated with CSF overproduction, is the first macroscopic evidence that ependymal cilia may be involved in the regulation of CSF production and flow. We suggest that brain imaging should be performed in all cases of RGMC and that a diagnosis of PCD or RGMC be strongly considered in patients with unexplained hydrocephalus and a lifelong "wet"-sounding cough.

We conclude that there is a high incidence of hydrocephalus, arachnoid cysts, and CPH in MCIDAS-associated RGMC. In all cases, the observed hydrocephalus seems arrested in childhood without progression or adverse neurologic sequelae. Our new observation of CPH, which is associated with CSF overproduction, is the first macroscopic evidence that ependymal cilia may be involved in the regulation of CSF production and flow. We suggest that brain imaging should be performed in all cases of RGMC and that a diagnosis of PCD or RGMC be strongly considered in patients with unexplained hydrocephalus and a lifelong "wet"-sounding cough.

To demonstrate the causal role in disease of the

m.15992A>T mutation observed in patients from 5 independent families.

Lactate measurement, muscle histology, and mitochondrial activities in patients; PCR-based analyses of the size, amount, and sequence of muscle mitochondrial DNA (mtDNA) and proportion of the mutation; respiration, mitochondrial activities, proteins, translation, transfer RNA (tRNA) levels, and base modification state in skin fibroblasts and cybrids; and reactive oxygen species production, proliferation in the absence of glucose, and plasma membrane potential in cybrids.

All patients presented with severe exercise intolerance and hyperlactatemia. They were associated with prominent exercise-induced muscle swelling, conspicuous in masseter muscles (2 families), and/or with congenital cataract (2 families). MRI confirmed exercise-induced muscle edema. Muscle disclosed severe combined respiratory defect. Muscle mtDNA had normal size and amount. Its sequence was almost identical in all patients, defining the haplotype as J1c10, and sharing 31 variants, only 1 of which,

m.15992A>T, was likely pathogenic. The mutation was homoplasmic in all tissues and family members. Fibroblasts and cybrids with homoplasmic mutation had defective respiration, low complex III activity, and decreased tRNA

amount. Their respiratory complexes amount and tRNA

aminoacylation appeared normal. Low proliferation in the absence of glucose demonstrated the relevance of the defects on cybrid biology while abnormal loss of cell volume when faced to plasma membrane depolarization provided a link to the muscle edema observed in patients.

The homoplasmic

m.15992A>T mutation in the J1c10 haplotype causes exercise-induced muscle swelling and fatigue.

T mutation in the J1c10 haplotype causes exercise-induced muscle swelling and fatigue.

Based on the Minorities' Diminished Returns (MDRs) framework, indicators of high socioeconomic status (SES), such as high maternal educational attainment, show weaker protective effects on various developmental, behavioral, and health outcomes for Black than White families. As a result of these MDRs, families and individuals with high educational attainment still report high levels of depression, smoking, obesity, and chronic disease. Limited knowledge exists on MDRs of maternal education on indicators of wealth such as home ownership and home value.

Built on the MDRs framework, we tested the hypothesis of whether the effects of maternal educational attainment at birth on home ownership and home value, as proxies of wealth, vary between Black and White families. We hypothesized that 1) high maternal education would be associated with more wealth 15 years later, and 2) compared to Whites, Blacks would be less likely to accumulate wealth (own a house) across all educational levels, given a weaker boosting eaccumulation in Black families may be a mechanism that contributes to racial health disparities in high socioeconomic status and also poor outcomes of high SES Black families. selleckchem That is, a smaller effect of maternal educational attainment on changing the real lives of Black than White youth may be one of the mechanisms by which health remains worse than expected in high SES Black families. Not all of the health, behavioral, and developmental disparities are due to the racial gap in SES but also diminishing returns of socioeconomic status indicators such as maternal educational attainment for racial minorities. Research should study how social stratification, discriminatory mortgage and banking, residential segregation, family formation, employment, and occupational prestige reduce Black families' ability to mobilize their human capital and secure tangible economic and non-economic outcomes.Mammographic density (MD) influences breast cancer risk, but how this is mediated is unknown. Molecular differences between breast cancers arising in the context of the lowest and highest quintiles of mammographic density may identify the mechanism through which MD drives breast cancer development. Women diagnosed with invasive or in situ breast cancer where MD measurement was also available (n = 842) were identified from the Lifepool cohort of >54,000 women participating in population-based mammographic screening. This group included 142 carcinomas in the lowest quintile of MD and 119 carcinomas in the highest quintile. Clinico-pathological and family history information were recorded. Tumor DNA was collected where available (n = 56) and sequenced for breast cancer predisposition and driver gene mutations, including copy number alterations. Compared to carcinomas from low-MD breasts, those from high-MD breasts were significantly associated with a younger age at diagnosis and features associated with poor prognosis. Low- and high-MD carcinomas matched for grade, histological subtype, and hormone receptor status were compared for somatic genetic features. Low-MD carcinomas had a significantly increased frequency of TP53 mutations, higher homologous recombination deficiency, higher fraction of the genome altered, and more copy number gains on chromosome 1q and losses on 17p. While high-MD carcinomas showed enrichment of tumor-infiltrating lymphocytes in the stroma. The data demonstrate that when tumors were matched for confounding clinico-pathological features, a proportion in the lowest quintile of MD appear biologically distinct, reflective of microenvironment differences between the lowest and highest quintiles of MD.