The landscape and clinical utility of comprehensive genomic investigations for a wide range of pediatric rheumatic disorders have not been fully characterized in the Middle East. Here seventy‐one pediatric patients, of diverse Arab origins, were clinically and genetically assessed for a spectrum of rheumatology‐related diseases at the only dedicated tertiary children's hospital in the United Arab Emirates

ABCC8 encodes the SUR1 subunit of the β‐cell ATP‐sensitive potassium channel whose loss of function causes congenital hyperinsulinism (CHI). Molecular diagnosis is critical for optimal management of CHI patients. Unfortunately, assessing the impact of ABCC8 variants on RNA splicing remains very challenging as this gene is poorly expressed in leukocytes.

Ferrodoxin reductase (FDXR) deficiency is a mitochondrial disease described in recent years primarily in association with optic atrophy, acoustic neuropathy, and developmental delays. Here, we identified seven unpublished patients with FDXR deficiency belonging to six independent families. These patients show a broad clinical spectrum ranging from Leigh syndrome with early demise and severe infantile‐onset

Idiopathic scoliosis (IS) is a spinal disorder affecting up to 3% of otherwise healthy children. IS has a strong familial genetic component and is believed to be genetically complex due to significant variability in phenotype and heritability. Previous studies identified putative loci and variants possibly contributing to IS susceptibility, including within ECM, cilia and actin networks, but the genetic

The discovery of high‐risk breast cancer susceptibility genes, such as Breast cancer associated gene 1 (BRCA1) and Breast cancer associated gene 2 (BRCA2) has led to accurate identification of individuals for risk management and targeted therapy. The rapid decline in sequencing costs has tremendously increased the number of individuals who are undergoing genetic testing world‐wide. However, given the

Mendelian rare genetic diseases affect 5‐10% of the population, and with over 5,300 genes responsible for ∼7,000 different diseases, they are challenging to diagnose. The use of whole genome sequencing (WGS) has bolstered the diagnosis rate significantly. Effective use of WGS relies upon the ability to identify the disrupted gene responsible for disease phenotypes. This process involves genomic variant

In (Gao et al., 2017), Caixia Xu is a co‐corresponding author with below details. She had been mistakenly listed as a co‐author and we′re correcting the error with release of a corrigendum. Caixia Xu3* 3 Research Centre for Translational Medicine, First Affiliated Hospital, Sun Yat‐Sen University, Guangzhou, China *Correspondence: Caixia Xu, Research Centre for Translational Medicine, First Affiliated

Documenting variation in our genomes is important for research and clinical care. Accuracy in the description of DNA variants is therefore essential. To address this issue, the Human Variome Project convened a committee to evaluate the feasibility of requiring authors to verify that all variants submitted for publication complied with a widely accepted standard for description. After a pilot study

Glutamatergic neurotransmission is crucial for brain development, wiring neuronal function, and synaptic plasticity mechanisms. Recent genetic studies showed the existence of autosomal dominant de novo GRIN gene variants associated with GRIN‐related disorders (GRDs), a rare pediatric neurological disorder caused by N‐methyl‐ d‐aspartate receptor (NMDAR) dysfunction. Notwithstanding, GRIN variants identification

Sequence variants of ZMYND15 cause azoospermia in humans, but they have not yet been reported in infertile men with severe oligozoospermia (SO). We performed whole‐exome and Sanger sequencing to identify suspected causative variants in 414 idiopathic participating infertile men with SO or azoospermia. Three novel homozygous truncating variants in ZMYND15 were identified in three of the 219 (1.37%)

Genome‐wide association studies (GWAS) have identified single‐nucleotide polymorphisms (SNPs) associated with glioma risk on 20q13.33, but the biological mechanisms underlying this association are unknown. We tested the hypothesis that a functional SNP on 20q13.33 impacted the activity of an enhancer, leading to an altered expression of nearby genes. To identify candidate functional SNPs, we identified

Signal sequence receptor protein 4 (SSR4) is a subunit of the translocon‐associated protein complex, which participates in the translocation of proteins across the endoplasmic reticulum membrane, enhancing the efficiency of N‐linked glycosylation. Pathogenic variants in SSR4 cause a congenital disorder of glycosylation: SSR4–congenital disorders of glycosylation (CDG). We describe three SSR4–CDG boys

In order to reconstruct the phenotypical and clinical implications of the Italian genetic structure, we thoroughly analyzed a whole‐exome sequencing dataset comprised of 1,686 healthy Italian individuals. We found six previously unreported variants with remarkable frequency differences between Northern and Southern Italy in the HERC2, OR52R1, ADH1B and THBS4 genes. We reported 36 clinically relevant

PALB2 has been identified as a breast and pancreatic cancer susceptibility gene. Utilizing a targeted sequencing approach, we discovered two novel germline missense PALB2 variants c.191C>T and c.311C>T, encoding p.Ser64Leu and p.Pro104Leu, respectively, in individuals in a pancreatic cancer registry. No missense PALB2 variants from familial pancreatic cancer patients, and few PALB2 variants overall

Spinal muscular atrophy (SMA) is a severe neuromuscular autosomal recessive disorder affecting 1/10,000 live births. Most SMA patients present homozygous deletion of SMN1, while the vast majority of SMA carriers present only a single SMN1 copy. The sequence similarity between SMN1 and SMN2, and the complexity of the SMN locus makes the estimation of the SMN1 copy‐number by next‐generation sequencing

As whole‐genome data become available for increasing numbers of individuals across diverse populations, the list of genomic variants of unknown significance (VOUS) continues to grow. One powerful tool in VOUS interpretation is determining whether an allele is too common to be considered pathogenic. As genetic and epidemiological parameters vary across disease models, so too does the pathogenic allele

Ciliopathies are clinically and genetically heterogeneous diseases. We studied three patients from two independent families presenting with features of Joubert syndrome: abnormal breathing pattern during infancy, developmental delay/intellectual disability, cerebellar ataxia, molar tooth sign on magnetic resonance imaging scans, and polydactyly. We identified biallelic loss‐of‐function (LOF) variants

This letter to the editor (Johnson & Ngo, 2020) was published in Human Mutation volume 41, issue 8 along with a response letter, but the order of articles in the Table of Contents (TOC) was incorrect. This letter should have been listed immediately before the response letter to the editor by Le et al. (2020) Also, co‐author Linh T. Ngo of the present Letter is not currently working in academia, so

This response letter to the editor [Le et al., 2020] was published in Human Mutation volume 41, issue 8 along with the originating letter, but the order of articles in the Table of Contents (TOC) was incorrect. This response letter should have been listed immediately following the original letter to the editor by Johnson and Ngo (2020). Also, the reference citation in this letter to Johnson and Ngo

More than two decades ago, a recessive syndromic phenotype affecting kidneys, eyes, and ears, was first described in the endogamous Afrikaner population of South Africa. Using whole‐exome sequencing of DNA from two affected siblings (and their carrier parents), we identified the novel RRM2B c.786G>T variant as a plausible disease‐causing mutation. The RRM2B gene is involved in mitochondrial integrity

LMX1A, encoding the LIM homeobox transcription factor, is essential for inner ear development. Despite previous reports of three human LMX1A variants with nonsyndromic hearing loss (NSHL) in the literature, functional characterization of these variants has never been performed. Encouraged by identification of a de novo, heterozygous, missense variant (c.595A > G; p.Arg199Gly) located in the homeodomain

Goldberg–Shprintzen syndrome (GOSHS) is caused by loss of function variants in the kinesin binding protein gene (KIFBP). However, the phenotypic range of this syndrome is wide, indicating that other factors may play a role. To date, 37 patients with GOSHS have been reported. Here, we document nine new patients with variants in KIFBP: seven with nonsense variants and two with missense variants. To our

Mutations in RBM20 encoding the RNA‐binding motif protein 20 (RBM20) are associated with an early onset and clinically severe forms of cardiomyopathies. Transcriptome analyses revealed RBM20 as an important regulator of cardiac alternative splicing. RBM20 mutations are especially localized in exons 9 and 11 including the highly conserved arginine and serine‐rich domain (RS domain). Here, we investigated

Genetic variants contribute to the risk of chronic pancreatitis (CP) in adults and children. The risk variant CEL‐HYB1, a recombinant hybrid allele of CEL and its neighboring pseudogene (CELP), encodes a pathogenic variant of the pancreatic digestive enzyme carboxyl ester lipase (CEL). We previously identified combinations of two non‐synonymous SNPs, c.1463T>C (p. Ile488Thr) and c.1643C>T (p. Thr548Ile)

Retraction: Montagna G., Di Biase A., Cappa M., Melone M. A., Piantadosi C., Colabianchi D., Patrono C., Attori L., Cannelli N., Cotrufo R., & Salvati S. (2005). Identification of seven novel mutations in ABCD1 by a DHPLC‐based assay in Italian patients with X‐linked adrenoleukodystrophy. Human Mutation, 25(2), 222. (https://onlinelibrary.wiley.com/doi/abs/10.1002/humu.9303). The above article, published

Genetic variation in the highly conserved Sonic Hedgehog (SHH) gene is one of the most common genetic causes for the malformations of the brain and face in humans described as the holoprosencephaly clinical spectrum. However, only a minor fraction of known SHH variants have been experimentally proven to lead to abnormal function. Employing a phenotypic rescue assay with synthetic human messenger RNA

In cystic fibrosis (CF), the correction of splicing defects represents an interesting therapeutic approach to restore normal CFTR function. In this study, we focused on 10 common mutations/variants 711+3A>G/C, 711+5G>A, TG13T3, TG13T5, TG12T5, 1863C>T, 1898+3A>G, 2789+5G>A, and 3120G>A that induce skipping of the corresponding CFTR exons 5, 10, 13, 16, and 18. To rescue the splicing defects we tested