Mutations in the gene SCAPER (S phase Cyclin A-Associated Protein residing in the Endoplasmic Reticulum) have recently been associated with retinitis pigmentosa (RP) and intellectual disability (ID). In 2011, a possible involvement of SCAPER in human diseases was discovered for the first time due to the identification of a homozygous mutation causing ID in an Iranian family. Later, five studies were published in 2019 that described patients with autosomal recessive syndromic retinitis pigmentosa (arRP) accompanied by ID and attention-deficit/hyperactivity disorder (ADHD). This present study describes three patients from an Arab consanguineous family in Israel with similar clinical features of the SCAPER syndrome. In addition, new manifestations of ocular symptoms, nystagmus, glaucoma, and elevator palsy, were observed. Genetic testing of the patients and both parents via whole-exome sequencing revealed the homozygous mutation c.2023-2A>G in SCAPER. Phenotypic and genotypic descriptions for all available cases described in the literature including our current three cases (37 cases) were carried out, in addition to a bioinformatics analysis for all the genetic variants that was undertaken. Our study confirms and extends the clinical manifestations of SCAPER-related disorders.

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BACKGROUND: NOTCH3 variants are known to be linked to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, some null NOTCH3 variants with homozygous inheritance cause neurological symptoms distinct from CADASIL. The aim of this study was to expand the clinical spectrum of this distinct condition and provide further evidence of its autosomal recessive inheritance.
RESULTS: Whole exome sequencing (WES) was performed on a proband who exhibited livedo racemosa, ataxia, cognitive decline, seizures, and MRI white matter abnormalities without anterior temporal pole lesions. Segregation analysis was conducted with Sanger sequencing. WES of the proband identified a novel homozygous NOTCH3 null variant (c.2984delC). The consanguineous parents were confirmed as heterozygous variant carriers. In addition, three heterozygous NOTCH3 null variants were reported as incidental findings in three unrelated cases analyzed in our center.
CONCLUSIONS: The findings of this study suggest an autosomal recessive inheritance pattern in this early-onset leukoencephalopathy, in contrast to CADASIL\'s dominant gain-of-function mechanism; which is a clear example of genotype-phenotype correlation. Comprehensive genetic analysis provides valuable insights into disease mechanisms and facilitates diagnosis and family planning for NOTCH3-associated neurological disorders.

UNASSIGNED: The identification and analysis of allelic variation are important bases for crop diversity research, trait domestication and molecular marker development. Grain tannin content is a very important quality trait in sorghum. Higher tannin levels in sorghum grains are usually required when breeding varieties resistant to bird damage or those used for brewing liquor. Non-tannin-producing or low-tannin-producing sorghum accessions are commonly used for food and forage. Tan1 and Tan2, two important cloned genes, regulate tannin biosynthesis in sorghum, and mutations in one or two genes will result in low or no tannin content in sorghum grains. Even if sorghum accessions contain dominant Tan1 and Tan2, the tannin contents are distributed from low to high, and there must be other new alleles of the known regulatory genes or new unknown genes contributing to tannin production.
UNASSIGNED: The two parents 8R306 and 8R191 did not have any known recessive alleles for Tan1 and Tan2, and it was speculated that they probably both had dominant Tan1 and Tan2 genotypes. However, the phenotypes of two parents were different; 8R306 had tannins and 8R191 had non-tannins in the grains, so these two parents were constructed as a RIL population. Bulked segregant analysis (BSA) was used to determine other new alleles of Tan1 and Tan2 or new Tannin locus. Tan1 and Tan2 full-length sequences and tannin contents were detected in wild sorghum resources, landraces and cultivars.
UNASSIGNED: We identified two novel recessive tan1-d and tan1-e alleles and four recessive Tan2 alleles, named as tan2-d, tan2-e, tan2-f, and tan2-g. These recessive alleles led to loss of function of Tan1 and Tan2, and low or no tannin content in sorghum grains. The loss-of-function alleles of tan1-e and tan2-e were only found in Chinese landraces, and other alleles were found in landraces and cultivars grown all around the world. tan1-a and tan1-b were detected in foreign landraces, Chinese cultivars and foreign cultivars, but not in Chinese landraces.
UNASSIGNED: These results implied that Tan1 and Tan2 recessive alleles had different geographically distribution in the worldwide, but not all recessive alleles had been used in breeding. The discovery of these new alleles provided new germplasm resources for breeding sorghum cultivars for food and feed, and for developing molecular markers for low-tannin or non-tannin cultivar-assisted breeding in sorghum.

Movement disorders such as bradykinesia, tremor, dystonia, chorea, and myoclonus most often arise in several neurodegenerative diseases with basal ganglia and white matter involvement. While the pathophysiology of these disorders remains incompletely understood, dysfunction of the basal ganglia and related brain regions is often implicated. The VPS13D gene, part of the VPS13 family, has emerged as a crucial player in neurological pathology, implicated in diverse phenotypes ranging from movement disorders to Leigh syndrome. We present a clinical case of VPS13D-associated disease with two variants in the VPS13D gene in an adult female. This case contributes to our evolving understanding of VPS13D-related diseases and underscores the importance of genetic screening in diagnosing and managing such conditions.

Recessive genic male sterility (RGMS) provides an effective approach for the commercial exploitation of heterosis, especially in Brassica crops. Although some artificial RGMS mutants have been reported in B. rapa, no causal genes derived from these natural mutants have been identified so far. In this study, a spontaneous RGMS mutant Bcajh97-01A derived from the \'Aijiaohuang\' line traced back to the 1980 s was identified. Genetic analysis revealed that the RGMS trait was controlled by a single locus in the Bcajh97-01A/B system. Bulk segregant analysis (BSA) in combination with linkage analysis was employed to delimit the causal gene to an approximate 129 kb interval on chromosome A02. The integrated information of transcriptional levels and the predicted genes in the target region indicated that the Brmmd1 (BraA02g017420) encoding a PHD-containing nuclear protein was the most likely candidate gene. A 374 bp miniature inverted-repeat transposable element (MITE) was inserted into the first exon to prematurely stop the Brmmd1 gene translation, thus blocking the normal expression of this gene at the tetrad stage in the Bcajh97-01A. Additionally, a co-segregating structure variation (SV) marker was developed to rapidly screen the RGMS progenies from Bcajh97-01A/B system. Our findings reveal that BraA02g017420 is the causal gene responsible for the RGMS trait. This study lays a foundation for marker-assisted selection and further molecular mechanism exploration of pollen development in B. rapa.

CONCLUSIONS: The gene controlling pink flesh in watermelon was finely mapped to a 55.26-kb region on chromosome 6. The prime candidate gene, Cla97C06G122120 (ClPPR5), was identified through forward genetics. Carotenoids offer numerous health benefits; while, they cannot be synthesized by the human body. Watermelon stands out as one of the richest sources of carotenoids. In this study, genetic generations derived from parental lines W15-059 (red flesh) and JQ13-3 (pink flesh) revealed the presence of the recessive gene Clpf responsible for the pink flesh (pf) trait in watermelon. Comparative analysis of pigment components and microstructure indicated that the disparity in flesh color between the parental lines primarily stemmed from variations in lycopene content, as well as differences in chromoplast number and size. Subsequent bulk segregant analysis (BSA-seq) and genetic mapping successfully narrowed down the Clpf locus to a 55.26-kb region on chromosome 6, harboring two candidate genes. Through sequence comparison and gene expression analysis, Cla97C06G122120 (annotated as a pentatricopeptide repeat, PPR) was predicted as the prime candidate gene related to pink flesh trait. To further investigate the role of the PPR gene, its homologous gene in tomato was silenced using a virus-induced system. The resulting silenced fruit lines displayed diminished carotenoid accumulation compared with the wild-type, indicating the potential regulatory function of the PPR gene in pigment accumulation. This study significantly contributes to our understanding of the forward genetics underlying watermelon flesh traits, particularly in relation to carotenoid accumulation. The findings lay essential groundwork for elucidating mechanisms governing pigment synthesis and deposition in watermelon flesh, thereby providing valuable insights for future breeding strategies aimed at enhancing fruit quality and nutritional value.

Recessive dystrophic epidermolysis bullosa is a rare genodermatosis caused by a mutation of the Col7a1 gene. The Col7a1 gene codes for collagen type VII protein, a major component of anchoring fibrils. Mutations of the Col7a1 gene can cause aberrant collagen type VII formation, causing an associated lack or absence of anchoring fibrils. This presents clinically as chronic blistering, scarring, and fibrosis, often leading to the development of cutaneous squamous cell carcinoma. Patients also experience persistent pain and pruritus. Pain management and supportive bandaging remain the primary treatment options. The pathology of recessive dystrophic epidermolysis bullosa was first described in the 1980s, and there has since been a multitude of encouraging treatment options developed. However, in vivo research has been hindered by inadequate models of the disease. The various mouse models in existence possess longevity and surface area constraints, or do not adequately model a normal human disease state. In this paper, we describe a novel rat model of recessive dystrophic epidermolysis bullosa that offers an alternative to previous murine models. An 8-base pair deletion was induced in the Col7a1 gene of Lewis rats, which was subsequently found to cause a premature stop codon downstream. Homozygous mutants presented with a fragile and chronically blistered phenotype postnatally. Further histological analysis revealed subepidermal clefting and the absence of anchoring fibrils. The generation of this novel model offers researchers an easily maintained organism that possesses a larger surface area for experimental topical and transfused therapies to be tested, which may provide great utility in the future study of this debilitating disease.

BACKGROUND: Bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is one of the most devastating diseases of rice leading to huge yield losses in Southeast Asia. The recessive resistance gene xa-45(t) from Oryza glaberrima IRGC102600B, mapped on rice chromosome 8, spans 80 Kb with 9 candidate genes on Nipponbare reference genome IRGSP-1.0. The xa-45(t) gene provides durable resistance against all the ten Xanthomonas pathotypes of Northern India, thus aiding in the expansion of recessive bacterial blight resistance gene pool. Punjab Rice PR127, carrying xa-45(t), was released for wider use in breeding programs. This study aims to precisely locate the target gene among the 9 candidates conferring resistance to bacterial blight disease.
RESULTS: Sanger sequencing of all nine candidate genes revealed seven SNPs and an Indel between the susceptible parent Pusa 44 and the resistant introgression line IL274. The genotyping with polymorphic markers identified three recombinant breakpoints for LOC_Os08g42370, and LOC_Os08g42400, 15 recombinants for LOC_Os08g423420 and 26 for LOC_Os08g42440 out of 190 individuals. Relative expression analysis across six time intervals (0, 8, 24, 48, 72, and 96 h) after bacterial blight infection showed over expression of LOC_Os08g42410-specific transcripts in IL274 compared to Pusa 44, with a significant 4.46-fold increase observed at 72 h post-inoculation.
CONCLUSIONS: The Indel marker at the locus LOC_Os08g42410 was found co-segregating with the phenotype, suggesting its candidacy towards xa-45(t). The transcript abundance assay provides strong evidence for the involvement of LOC_Os08g42410 in the resistance conferred by the bacterial blight gene xa-45(t).

Epidermolysis bullosa (EB) is an umbrella term for a group of rare inherited skin disorders characterised by mucocutaneous fragility. Patients suffer from blisters and chronic wounds that arise spontaneously or following minor mechanical trauma, often resulting in inflammation, scarring and fibrosis due to poor healing. The recessive form of dystrophic EB (RDEB) has a particularly severe phenotype and is caused by mutations in the COL7A1 gene, encoding the collagen VII protein, which is responsible for adhering the epidermis and dermis together. One of the most feared and devastating complications of RDEB is the development of an aggressive form of cutaneous squamous cell carcinoma (cSCC), which is the main cause of mortality in this patient group. However, pathological drivers behind the development and progression of RDEB-associated cSCC (RDEB-cSCC) remain somewhat of an enigma, and the evidence to date points towards a complex process. Currently, there is no cure for RDEB-cSCC, and treatments primarily focus on prevention, symptom management and support. Therefore, there is an urgent need for a comprehensive understanding of this cancer\'s pathogenesis, with the aim of facilitating the discovery of drug targets. This review explores the current knowledge of RDEB-cSCC, emphasising the important role of the immune system, genetics, fibrosis, and the tumour-promoting microenvironment, all ultimately intricately interconnected.