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Breeding for dwarfing traits in sorghum is crucial. However, only three genes (Dw1–Dw3) that control plant height have been mapped. In this study, 634 sorghum cultivars were collected to investigate plant height and genotypes. Four were genotyped Dw1DW2Dw3 (wild type) but with different plant heights, and they were selected to construct two populations and map new dwarf genes. Bulked segregant analysis with whole-genome resequencing of the two populations identified the candidate gene in one same genomic region—on chromosome 7. Then, it was narrowed down to a region containing nine genes. Amino acid and DNA sequence analysis of the parent and offspring plants revealed that two novel allelic mutations in the Dw3 gene play a role in reducing the plant height—8R262 or 8R417, including 1 bp substitution and 2 bp deletions. Furthermore, we sequenced 19 cultivars that primarily exhibited a "one-dwarf" hybrid or wild-type and presumed another allelic mutation via the amino acid alignment of 8R019, 8R100, and 8R402, which was another one-base substitution. These results indicate that multiple types of allelic mutations in the Dw3 gene should be considered when identified or applied. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the genetic diversity of isolates of Mycobacterium tuberculosis (Mtb) from presumed drug-resistant tuberculosis patients from several states of Brazil. The isolates had been submitted to conventional drug susceptibility testing for first- and second-line drugs. Multidrug-resistant (MDR-TB) (54.8%) was the most frequent phenotypic resistance profile, in addition to an important high frequency of pre-extensive resistance (p-XDR-TB) (9.2%). Using whole-genome sequencing (WGS), we characterized 298 Mtb isolates from Brazil. Besides the analysis of genotype distribution and possible correlations between molecular and clinical data, we determined the performance of an in-house WGS pipeline with other online pipelines for Mtb lineages and drug resistance profile definitions. Sub-lineage 4.3 (52%) was the most frequent genotype, and the genomic approach revealed a p-XDR-TB level of 22.5%. We detected twenty novel mutations in three resistance genes, and six of these were observed in eight phenotypically resistant isolates. A cluster analysis of 170 isolates showed that 43.5% of the TB patients belonged to 24 genomic clusters, suggesting considerable ongoing transmission of DR-TB, including two interstate transmissions. The in-house WGS pipeline showed the best overall performance in drug resistance prediction, presenting the best accuracy values for five of the nine drugs tested. Significant associations were observed between suffering from fatal disease and genotypic p-XDR-TB (p = 0.03) and either phenotypic (p = 0.006) or genotypic (p = 0.0007) ethambutol resistance. The use of WGS analysis improved our understanding of the population structure of MTBC in Brazil and the genetic and clinical data correlations and demonstrated its utility for surveillance efforts regarding the spread of DR-TB, hopefully helping to avoid the emergence of even more resistant strains and to reduce TB incidence and mortality rates. [ABSTRACT FROM AUTHOR]

Simple Summary: Cleidocranial dysplasia is a rare disease, manifested by anomalies in the skull, face, teeth, thorax, clavicle, extremities, and short stature. The disease is caused by mutations in the RUNX2 gene, which is involved in the differentiation of cells that give rise and formation of bones. In this study, the genetic material of four patients and their families was analyzed, with the purpose of identifying changes in the sequence of the RUNX2 gene, finding three new changes and one change already reported in the literature. One patient presented cataract and damage to the retina of the eye, and data were not reported in other patients. A bioinformatic analysis of the RUNX2 protein was carried out with the aim of predicting mechanisms, such as the function, stability, and conformation of the protein, and of trying to understand its relationship with the variable presentation of signs and symptoms in this condition. These results can be useful in the genetic counselling of patients. Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia characterized by persistent open skull sutures with bulging calvaria, hypoplasia, or aplasia of clavicles permitting abnormal opposition of the shoulders; wide public symphysis; short middle phalanx of the fifth fingers; and vertebral, craniofacial, and dental anomalies. It is a rare disease, with a prevalence of 1–9/1,000,000, high penetrance, and variable expression. The gene responsible for CCD is the Runt-related transcription factor 2 (RUNX2) gene. We characterize the clinical, genetic, and bioinformatic results of four CCD cases: two cases within Mexican families with six affected members, nine asymptomatic individuals, and two sporadic cases with CCD, with one hundred healthy controls. Genomic DNA analyses of the RUNX2 gene were performed for Sanger sequencing. Bioinformatics tools were used to predict the function, stability, and structural changes of the mutated RUNX2 proteins. Three novel heterozygous mutations (c.651_652delTA; c.538_539delinsCA; c.662T>A) and a previously reported mutation (c.674G>A) were detected. In silico analysis showed that all mutations had functional, stability-related, and structural alterations in the RUNX2 protein. Our results show novel mutations that enrich the pool of RUNX2 gene mutations with CCD. Moreover, the proband 1 presented clinical data not previously reported that could represent an expanded phenotype of severe expression. [ABSTRACT FROM AUTHOR]

Simple Summary: The fall armyworm (FAW) is a pest that can cause severe damage to crops, particularly maize and cotton, resulting in agricultural losses. It has developed resistance to various types of insecticides due to certain gene mutations in its body. Our study aims to investigate how these genes affect the pest's sensitivity to insecticides. We utilized amplicon sequencing to analyze 21 sites within six related genes and identified both known and unknown mutations. Subsequently, molecular docking simulations were employed to assess the impact of these mutations on the binding ability between insecticides and proteins. Our findings indicate that these mutations reduce the binding ability, potentially contributing to increased insecticide resistance. Thus, our study could unveil the variation and evolution of resistance genes in FAW. The fall armyworm (FAW), Spodoptera frugiperda, is a worldwide agricultural pest that invaded China in 2018, and has developed resistance to multiple insecticides. The evolution of insecticide resistance is facilitated by mutations of target genes responsible for conferring resistance. In this study, amplicon sequencing analyzed 21 sites in six resistance genes. In addition to known mutations, unknown variants were also found, including novel variants: F290C (ace-1 gene, 0.1% frequency), I1040T/V (CHSA gene, 0.1% frequency), A309T (GluCl gene, 0.1% frequency), and I4790T/V (RyR gene, 0.1% frequency). Additionally, molecular docking was employed to investigate the impact of the aforementioned new mutations on insecticide binding to proteins. The analyses indicated that the binding abilities were reduced, similar to the resistance mutations that were reported, implying these novel mutations may confer transitional resistance. This study may provide a foundation for understanding the functions of these novel mutations in the evolutionary processes that drive the emergence of insecticide resistance in this invasive species. [ABSTRACT FROM AUTHOR]

Pathogenic variants in IMPDH1 are associated with autosomal dominant retinitis pigmentosa 10 (RP10), and Leber congenital amaurosis 11. This case report of a 13-year-old girl with Down's syndrome and keratoglobus is aimed at linking the novel variant IMPDH1 c.134A>G, p.(Tyr45Cys), a variant of uncertain significance, to a clinical phenotype and to provide grounds for the objective assignment of its benign features. RP10 is characterized by the early onset and rapid progression of ocular symptoms, beginning with nyctalopia in childhood, accompanied by typical RP fundus changes. As evidenced via thorough clinical examination and testing, none of the RP10 characteristics were present in our patient. On the contrary, our patient who was heterozygous for IMPDH1 c.134A>G, p.(Tyr45Cys) showed no signs of peripheral retinal dystrophy, and did not manifest any disease characteristics typical of the IMPDH1 gene mutation. Consequently, we conclude that the variant did not contribute to the phenotype. According to standards and guidelines for the interpretation of sequence variants, IMPDH1 c.134A>G, p.(Tyr45Cys) revealed likely benign features. [ABSTRACT FROM AUTHOR]

Tufting enteropathy (TE) is caused by recessive EPCAM mutations, and is characterized by intractable diarrhea of congenital onset and disorganization of enterocytes. TE generally requires parenteral nutrition (PN) during childhood or intestinal bowel transplantation. We report three unrelated families with six children with TE.We highlight the high rate of disease-related mortality. We observe adequate weight gain with PN, but low to normal and stunted body length, supporting the recent notion that a short stature might be intrinsic to TE. The diagnosis of TE in the index patients from each family was delayed for months to years, even when clinical data, duodenal biopsies, or exome sequencing data were obtained early on. We identified three novel pathogenic EPCAM variants: a deletion of exon 1 that removes the ATG initiation codon, a missense variant c.326A > G (p.Gln109Arg), and nonsense mutation c.429G > A (p.Trp143*) in a compound heterozygous state with the Mediterranean splice site variant c.556-14A > G (Tyr186Phefs*6). Homozygosity for p.Gln109Arg was associated with absent EPCAM staining, and compound heterozygosity for p.Trp143*/Tyr186Phefs*6 was associated with reduced EPCAM staining in duodenal biopsies; such observations might contribute to a genotype–phenotype correlation in larger cohorts of TE patients. This study extends the clinical and molecular spectrum of TE. [ABSTRACT FROM AUTHOR]

Xeroderma pigmentosum is a rare autosomal recessive skin disorder characterized by freckle-like dry pigmented skin, photosensitivity, and photophobia. Skin and ocular symptoms are confined to sun exposed areas of the body. Patients have markedly increased risk for UV-induced skin, ocular, and oral cancers. Some patients develop neurodegenerative symptoms, including diminished tendon reflexes and microcephaly. In this study, we describe clinical and genetic findings of 36 XP patients from Egypt, a highly consanguineous population from North Africa. Thorough clinical evaluation followed by Sanger sequencing of XPA and XPC genes were done. Six novel and seven previously reported mutations were identified. Phenotype-genotype correlation was investigated. We report clinical and molecular findings consistent with previous reports of countries sharing common population structure, and geographical and historical backgrounds with implications on common ancestral origins and historical migration flows. Clinical and genetic profiling improves diagnosis, management, counselling, and implementation of future targeted therapies. [ABSTRACT FROM AUTHOR]

Alström syndrome (ALMS) is an ultrarare disease with an estimated prevalence lower than 1 in 1,000,000. It is associated with disease-causing mutations in the Alström syndrome 1 (ALMS1) gene, which codifies for a structural protein of the basal body and centrosomes. The symptomatology involves nystagmus, type 2 diabetes mellitus (T2D), obesity, dilated cardiomyopathy (DCM), neurodegenerative disorders and multiorgan fibrosis. We refined the clinical and genetic diagnosis data of 12 patients from 11 families, all of them from Spain. We also studied the allelic frequency of the different variants present in this cohort and performed a haplotype analysis for the most prevalent allele. The genetic analysis revealed 2 novel homozygous variants located in the exon 8, p.(Glu929Ter) and p.(His1808GlufsTer20) in 2 unrelated patients. These 2 novel variants were classified as pathogenic after an in silico experiment (computer analysis). On the other hand, 2 alleles were detected at a high frequency in our cohort: p.(Tyr1714Ter) (25%) and p.(Ser3872TyrfsTer19) (16.7%). The segregation analysis showed that the pathogenic variant p.(Tyr1714Ter) in 3 families is linked to a rare missense polymorphism, p.(Asn1787Asp). In conclusion, 2 novel pathological mutations have been discovered in homozygosis, as well as a probable founder effect in 3 unrelated families. [ABSTRACT FROM AUTHOR]