Genomic regions associated with microdeletion/microduplication syndromes exhibit extreme diversity of structural variation.

Segmental duplications (SDs) are a class of long, repetitive DNA elements whose paralogs share a high level of sequence similarity with each other. SDs mediate chromosomal rearrangements that lead to structural variation in the general population as well as genomic disorders associated with multiple congenital anomalies, including the 7q11.23 (Williams-Beuren Syndrome, WBS), 15q13.

Disclosure to friends or family and consequences after interpersonal violence: intersections of sexual identity and race.

This study's purpose was to examine whether disclosures to friends or family post-victimization was associated with emotional and academic consequences (e.g. feeling detached from others, getting worse grades) among students grouped by sexual identity and race intersections.

It's like herding cats: Atheist minority stress, group involvement, and psychological outcomes.

Using minority stress theory with a sample of 522 atheist people from the United States, the present study examined the associations of discrimination, proximal minority stressors (stigma consciousness, internalized antiatheism, outness as atheist), and atheist group involvement with psychological distress and self-esteem. Atheist group involvement was associated positively with outness and self-esteem, and negatively with discrimination. Structural equation modeling indicated that discrimination and stigma consciousness yielded significant positive direct relations with distress, whereas outness yielded a significant negative direct relation with distress.

The 22q11 low copy repeats are characterized by unprecedented size and structural variability.

Low copy repeats (LCRs) are recognized as a significant source of genomic instability, driving genome variability and evolution. The Chromosome 22 LCRs (LCR22s) mediate nonallelic homologous recombination (NAHR) leading to the 22q11 deletion syndrome (22q11DS). However, LCR22s are among the most complex regions in the genome, and their structure remains unresolved.

Unpacking body image concerns and disordered eating for transgender women: The roles of sexual objectification and minority stress.

Synthesizing both objectification theory (Fredrickson & Roberts, 1997) and minority stress theory (Meyer, 2003), the present study used a pantheoretical model of dehumanization (Moradi, 2013) to examine body image concerns and disordered eating symptomatology with 205 transgender women from the United States. Objectification theory constructs (i.e.

Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities.

CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin B12) metabolism and other developmental defects. Mutations in HCFC1, a transcriptional co-regulator which interacts with multiple transcription factors, have been associated with cblX. HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor.

Discovery of a potentially deleterious variant in TMEM87B in a patient with a hemizygous 2q13 microdeletion suggests a recessive condition characterized by congenital heart disease and restrictive cardiomyopathy.

Restrictive cardiomyopathy (RCM) is a rare cause of heart muscle disease with the highest mortality rate among cardiomyopathy types. The etiology of RCM is poorly understood, although genetic causes have been implicated, and syndromic associations have been described. Here, we describe a patient with an atrial septal defect and restrictive cardiomyopathy along with craniofacial anomalies and intellectual disabilities.

Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder.

Background: Mitochondrial disease is often suspected in cases of severe epileptic encephalopathy especially when a complex movement disorder, liver involvement and progressive developmental regression are present. Although mutations in either mitochondrial DNA or POLG are often present, other nuclear defects in mitochondrial DNA replication and protein translation have been associated with a severe epileptic encephalopathy.

Methods And Results: We identified a proband with an epileptic encephalopathy, complex movement disorder and a combined mitochondrial respiratory chain enzyme deficiency.

Hcfc1b, a zebrafish ortholog of HCFC1, regulates craniofacial development by modulating mmachc expression.

Mutations in HCFC1 (MIM300019), have been recently associated with cblX (MIM309541), an X-linked, recessive disorder characterized by multiple congenital anomalies including craniofacial abnormalities. HCFC1 is a transcriptional co-regulator that modulates the expression of numerous downstream target genes including MMACHC, but it is not clear how these HCFC1 targets play a role in the clinical manifestations of cblX. To begin to elucidate the mechanism by which HCFC1 modulates disease phenotypes, we have carried out loss of function analyses in the developing zebrafish.

Negotiating multiple marginalizations: experiences of South Asian LGBQ individuals.

Drawing from minority stress (Meyer, 2003) and feminist multicultural (Brown, 1994) theories, the present study investigated the additive and interactive relations between 2 types of external minority stress (heterosexist discrimination and racist events) and 4 internal stress processes related to identifying as a South Asian American lesbian, gay, bisexual, and queer (LGBQ) person (internalized heterosexism, acculturation, enculturation, and outness as LGBQ) with psychological distress. With 142 participants, Pearson's correlations, multiple regression, and simultaneous multiple moderation analyses were conducted. Experiences of heterosexist discrimination, racist events, and internalized heterosexism were correlated positively with psychological distress and enculturation was correlated negatively.

An individual with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and additional features expands the phenotype associated with mutations in KAT6B.

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal dominant disorder caused by mutations in FOXL2. We identified an individual with BPES and additional phenotypic features who did not have a FOXL2 mutation. We used whole exome sequencing to identify a de novo mutation in KAT6B (lysine acetyltransferase 6B) in this individual.

Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5.

Patients with nonketotic hyperglycinemia and deficient glycine cleavage enzyme activity, but without mutations in AMT, GLDC or GCSH, the genes encoding its constituent proteins, constitute a clinical group which we call 'variant nonketotic hyperglycinemia'. We hypothesize that in some patients the aetiology involves genetic mutations that result in a deficiency of the cofactor lipoate, and sequenced genes involved in lipoate synthesis and iron-sulphur cluster biogenesis. Of 11 individuals identified with variant nonketotic hyperglycinemia, we were able to determine the genetic aetiology in eight patients and delineate the clinical and biochemical phenotypes.

Moving beyond the binary with disordered eating research: a test and extension of objectification theory with bisexual women.

In predicting disordered eating, the core model of objectification theory (Fredrickson & Roberts, 1997) has been replicated and extended in research across most sexual minority groups (e.g., Haines et al.

An X-linked cobalamin disorder caused by mutations in transcriptional coregulator HCFC1.

Derivatives of vitamin B12 (cobalamin) are essential cofactors for enzymes required in intermediary metabolism. Defects in cobalamin metabolism lead to disorders characterized by the accumulation of methylmalonic acid and/or homocysteine in blood and urine. The most common inborn error of cobalamin metabolism, combined methylmalonic acidemia and hyperhomocysteinemia, cblC type, is caused by mutations in MMACHC.

Genes and biological processes commonly disrupted in rare and heterogeneous developmental delay syndromes.

Rare copy number variations (CNVs) are a recognized cause of common human disease. Predicting the genetic element(s) within a small CNV whose copy number loss or gain underlies a specific phenotype might be achieved reasonably rapidly for single patients. Identifying the biological processes that are commonly disrupted within a large patient cohort which possess larger CNVs, however, requires a more objective approach that exploits genomic resources.

Recurrent interstitial 1p36 deletions: Evidence for germline mosaicism and complex rearrangement breakpoints.

Deletions of chromosome 1p36 are one of the most frequently encountered subtelomeric alterations. Clinical features of monosomy 1p36 include neurocognitive impairment, hearing loss, seizures, cardiac defects, and characteristic facial features. The majority of cases have occurred sporadically, implying that genomic instability plays a role in the prevalence of the syndrome.

A de novo 8.8-Mb deletion of 21q21.1-q21.3 in an autistic male with a complex rearrangement involving chromosomes 6, 10, and 21.

We report here on a normal-appearing male with pervasive developmental disorder who was found to have a de novo, apparently balanced complex rearrangement involving chromosomes 6, 10, and 21: 46,XY,ins(21;10)(q11.2;p11.2p13)t(6;21)(p23;q11.

High-resolution mapping and analysis of copy number variations in the human genome: a data resource for clinical and research applications.

We present a database of copy number variations (CNVs) detected in 2026 disease-free individuals, using high-density, SNP-based oligonucleotide microarrays. This large cohort, comprised mainly of Caucasians (65.2%) and African-Americans (34.

Copy number variation at 1q21.1 associated with neuroblastoma.

Common copy number variations (CNVs) represent a significant source of genetic diversity, yet their influence on phenotypic variability, including disease susceptibility, remains poorly understood. To address this problem in human cancer, we performed a genome-wide association study of CNVs in the childhood cancer neuroblastoma, a disease in which single nucleotide polymorphism variations are known to influence susceptibility. We first genotyped 846 Caucasian neuroblastoma patients and 803 healthy Caucasian controls at approximately 550,000 single nucleotide polymorphisms, and performed a CNV-based test for association.

Identification of familial and de novo microduplications of 22q11.21-q11.23 distal to the 22q11.21 microdeletion syndrome region.

Deletions of the 22q11.2 region distal to the 22q11.21 microdeletion syndrome region have recently been described in individuals with mental retardation and congenital anomalies.

A 3.1-Mb microdeletion of 3p21.31 associated with cortical blindness, cleft lip, CNS abnormalities, and developmental delay.

We report a 3.1-Mb de novo deletion of 3p21.31 in a 3.

Low copy repeats mediate distal chromosome 22q11.2 deletions: sequence analysis predicts breakpoint mechanisms.

Genomic disorders contribute significantly to genetic disease and, as detection methods improve, greater numbers are being defined. Paralogous low copy repeats (LCRs) mediate many of the chromosomal rearrangements that underlie these disorders, predisposing chromosomes to recombination errors. Deletions of proximal 22q11.

Rapid detection of submicroscopic chromosomal rearrangements in children with multiple congenital anomalies using high density oligonucleotide arrays.

Chromosomal rearrangements such as microdeletions and interstitial duplications are the underlying cause of many human genetic disorders. These disorders can manifest in the form of multiple congenital anomalies (MCA), which are a significant cause of morbidity and mortality in children. The major limitations of cytogenetic tests currently used for the detection of such chromosomal rearrangements are low resolution and limited coverage of the genome.