Effect of changes in the menstrual cycle and age on the signal intensity of amide proton transfer imaging in the normal uterus: a preliminary study.

PURPOSE: To analyze the effect of changes in the menstrual cycle and age on the signal intensity of amide proton transfer (APT) imaging in normal uterine structures. METHODS: Thirty-one healthy females (age: 21-50 years old) underwent regular pelvic MRI and APT sequences during their menstrual cycle. The APT values of the endometrium, myometrium, and junctional zone were measured. One-way and multi-way analyses of variance were used to analyze the data. Intraindividual difference and Pearson's correlation analyses were also conducted. RESULTS: The APT values of the uterine structures during the menstrual, proliferative, and secretory phases were 3.413 ± 0.682%, 4.776 ± 0.829%, and 5.218 ± 0.772% for the endometrium; 2.966 ± 0.533%, 3.597 ± 0.380%, and 4.324 ± 0.583% for the myometrium; and 1.703 ± 0.393%, 2.362 ± 0.486%, and 2.779 ± 0.528% for the junctional zone. The individual variation in the APT values of the normal uterus during the three menstrual phases was 1.1-1.7%.There were no significant differences in APT values of uterine structures with age. The APT values of the endometrium were greater than those of other structures (P < 0.05).The Pearson correlation coefficients between APT values of uterine structures and menstrual cycle were 0.686, 0.743, and 0.684, respectively. CONCLUSION: The menstrual cycle had a significant effect on the APT signal intensities of the uterine structures, whereas premenopausal age had no significant effect. Changes in the uterine structures during the menstrual cycle should be considered when using APT to diagnose suspected uterine lesions.

GGC Repeat Expansion of RILPL1 is Associated with Oculopharyngodistal Myopathy.

OBJECTIVE: Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ptosis, dysarthria, ophthalmoplegia, and distal muscle weakness. Recent studies revealed that GGC repeat expansions in 5'-UTR of LRP12, GIPC1, and NOTCH2NLC are associated with OPDM. Despite these advances, approximately 30% of OPDM patients remain genetically undiagnosed. Herein, we aim to investigate the genetic basis for undiagnosed OPDM patients in two unrelated Chinese Han families. METHODS: Parametric linkage analysis was performed. Long-read sequencing followed by repeat-primed polymerase chain reaction and amplicon length polymerase chain reaction were used to determine the genetic cause. Targeted methylation sequencing was implemented to detect epigenetic changes. The possible pathogenesis mechanism was investigated by quantitative polymerase chain reaction, immunoblotting, RNA fluorescence in situ hybridization, and immunofluorescence staining of muscle biopsy samples. RESULTS: The disease locus was mapped to 12q24.3. Subsequently, GGC repeat expansion in the promoter region of RILPL1 was identified in six OPDM patients from two families, findings consistent with a founder effect, designated as OPDM type 4. Targeted methylation sequencing revealed hypermethylation at the RILPL1 locus in unaffected individuals with ultralong expansion. Analysis of muscle samples showed no significant differences in RILPL1 mRNA or RILPL1 protein levels between patients and controls. Public CAGE-seq data indicated that alternative transcription start sites exist upstream of the RefSeq-annotated RILPL1 transcription start site. Strand-specific RNA-seq data revealed bidirectional transcription from the RILPL1 locus. Finally, fluorescence in situ hybridization/immunofluorescence staining showed that both sense and antisense transcripts formed RNA foci, and were co-localized with hnRNPA2B1 and p62 in the intranuclear inclusions of OPDM type 4 patients. INTERPRETATION: Our findings implicate abnormal GGC repeat expansions in the promoter region of RILPL1 as a novel genetic cause for OPDM, and suggest a methylation mechanism and a potential RNA toxicity mechanism are involved in OPDM type 4 pathogenesis. ANN NEUROL 2022;92:512-526.