Genetic and Functional Analyses of the Novel KLF11 Pro193Thr Variant
                    in a Three-Generation Family with MODY7

Guan, Gaopeng; Qin, Tiantian; Zhao, Liling; Park, Jin

doi:10.1055/a-1961-6281

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…The DNA was cut into a length of 200–300 bp on the Bioruptor UCD-200 (Diagenode), diluted, loaded, and sequenced on the HiSeq2500 platform (Illumina, San Diego, CA). Exome data processing and variant annotation were performed as previously described ( Hu et al, 2020 ; Zhang et al, 2020 ; Guan et al, 2022 ), focusing on LCAH pathogenic genes. Mutations are rare events with a frequency of less than 1% in 1,000 genomes ( http://browser.1000genomes.org ), Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org/ ), and Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/ ).…”

Section: Methodsmentioning

confidence: 99%

Clinical and functional analyses of the novel STAR c.558C>A in a patient with classic lipoid congenital adrenal hyperplasia

et al. 2023

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Objective: Congenital lipid adrenal hyperplasia (LCAH) is the most serious type of congenital adrenal hyperplasia and is caused by steroid-based acute regulatory (STAR) protein mutations. Herein, we report compound heterozygous mutations c.558C>A (p.S186 R) and c.772C>T (p.Q258*) in a newborn 46 XY patient diagnosed with classic LCAH and explore their clinical and functional characteristics.Methods: Peripheral blood samples were collected from LCAH patient and their families. The pathogenic variant identified by whole-exome sequencing was further confirmed by Sanger sequencing and pedigree verification. The functional consequence and ability to convert cholesterol into progesterone of the identified STAR Q258* and S186 R mutations were analyzed by cell transfection and in vitro assays.Results: The proband was presented with severe glucocorticoid and mineralocorticoid deficiency, high adrenocorticotropic hormone, and enlarged adrenals. Heterozygous mutations p. S186 R and p. Q258* in the STAR gene were identified in the patient, and her parents were carriers, which is consistent with an autosomal recessive disorder. The STAR p. Q258* mutation has been reported and generates a truncated protein. The p. S186 R mutation is a novel variant that disrupts STAR. The residual STAR activities of p. S186R, p. Q258*, and p. S186R/p.Q258* were 13.9%, 7.3%, and 11.2%, respectively, of the wild-type, proving the main negative effects of the mutant proteins.Conclusion: Our findings reveal the molecular mechanisms underlying LCAH pathogenesis, further expanding the genotype and clinical spectrum of LCAH.

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Section: Methodsmentioning

confidence: 99%

Clinical and functional analyses of the novel STAR c.558C>A in a patient with classic lipoid congenital adrenal hyperplasia

et al. 2023

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“…Moreover, by inhibiting insulin gene promoter activity, the insulin gene cannot be normally expressed, which reduces insulin levels. Additionally, high glucose stimulation can inhibit the function of the peroxidase promoter and reduce the ability of islet β cells to scavenge oxidative free radicals, which eventually leads to MODY7[ 4 ]. Another report identified a novel KLF11 Pro193Thr variant in a three generation family with MODY7[ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, high glucose stimulation can inhibit the function of the peroxidase promoter and reduce the ability of islet β cells to scavenge oxidative free radicals, which eventually leads to MODY7[ 4 ]. Another report identified a novel KLF11 Pro193Thr variant in a three generation family with MODY7[ 4 ]. These findings shed light on the molecular mechanisms underlying the pathogenesis of MODY7.…”

Section: Introductionmentioning

confidence: 99%

Novel gene mutation in maturity-onset diabetes of the young: A case report

Zhang¹,

Zhao²,

Li³

et al. 2023

World J Clin Cases

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BACKGROUND Maturity-onset diabetes of the young (MODY) is the most common monogenic type of diabetes. Recently, 14 gene mutations have been found to be associated with MODY. In addition, the KLF11 gene mutation is the pathogenic gene of MODY7. To date, the clinical and functional characteristics of the novel KLF11 mutation c. G31A have not yet been reported. CASE SUMMARY We report of a 30-year-old male patient with a one-year history of nonketosis-prone diabetes and a 3-generation family history of diabetes. The patient was found to carry a KLF11 gene mutation. Therefore, the clinical data of family members were collected and investigated. A total of four members of the family were found to have heterozygous mutations in the KLF11 gene c. G31A, which resulted in a change in the corresponding amino acid p.D11N. Three patients had diabetes mellitus, and one patient had impaired glucose tolerance. CONCLUSION The heterozygous mutation of the KLF11 gene c.G31A (p. D11N) is a new mutation site of MODY7. Subsequently, the main treatment included dietary interventions and oral drugs.

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Krüppel‐like factors family in health and disease

Xiang,

Yang,

Deng

et al. 2024

MedComm

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Krüppel‐like factors (KLFs) are a family of basic transcription factors with three conserved Cys2/His2 zinc finger domains located in their C‐terminal regions. It is acknowledged that KLFs exert complicated effects on cell proliferation, differentiation, survival, and responses to stimuli. Dysregulation of KLFs is associated with a range of diseases including cardiovascular disorders, metabolic diseases, autoimmune conditions, cancer, and neurodegenerative diseases. Their multidimensional roles in modulating critical pathways underscore the significance in both physiological and pathological contexts. Recent research also emphasizes their crucial involvement and complex interplay in the skeletal system. Despite the substantial progress in understanding KLFs and their roles in various cellular processes, several research gaps remain. Here, we elucidated the multifaceted capabilities of KLFs on body health and diseases via various compliable signaling pathways. The associations between KLFs and cellular energy metabolism and epigenetic modification during bone reconstruction have also been summarized. This review helps us better understand the coupling effects and their pivotal functions in multiple systems and detailed mechanisms of bone remodeling and develop potential therapeutic strategies for the clinical treatment of pathological diseases by targeting the KLF family.

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Genetic and Functional Analyses of the Novel KLF11 Pro193Thr Variant in a Three-Generation Family with MODY7

Cited by 4 publications

References 32 publications

Clinical and functional analyses of the novel STAR c.558C>A in a patient with classic lipoid congenital adrenal hyperplasia

Clinical and functional analyses of the novel STAR c.558C>A in a patient with classic lipoid congenital adrenal hyperplasia

Novel gene mutation in maturity-onset diabetes of the young: A case report

Krüppel‐like factors family in health and disease

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