Diagnosing amyotrophic lateral sclerosis (ALS) is challenging and requires distinguishing it from conditions like distal hereditary motor neuropathy type 5 (dHMN-V). A 21-year-old female initially diagnosed with ALS showed progressive upper limb weakness extending to the lower limbs. Trio exome sequencing revealed a de novo pathogenic Berardinelli-Seip congenital lipodystrophy 2 variant (c.263A>G, p.Asn88Ser), confirming dHMN-V. Minipolymyoclonus of small amplitudes in bilateral wrists and ankles was an atypical presentation. This case underscores the importance of considering dHMN-V as a differential diagnosis in ALS-like distal upper extremity weakness.

Diagnosing amyotrophic lateral sclerosis (ALS) is challenging and requires distinguishing it from conditions like distal hereditary motor neuropathy type 5 (dHMN-V). A 21-year-old female initially diagnosed with ALS showed progressive upper limb weakness extending to the lower limbs. Trio exome sequencing revealed a de novo pathogenic Berardinelli-Seip congenital lipodystrophy 2 variant (c.263A>G, p.Asn88Ser), confirming dHMN-V. Minipolymyoclonus of small amplitudes in bilateral wrists and ankles was an atypical presentation. This case underscores the importance of considering dHMN-V as a differential diagnosis in ALS-like distal upper extremity weakness.

Diagnosing amyotrophic lateral sclerosis (ALS) is challenging and requires distinguishing it from conditions like distal hereditary motor neuropathy type 5 (dHMN-V). A 21-year-old female initially diagnosed with ALS showed progressive upper limb weakness extending to the lower limbs. Trio exome sequencing revealed a de novo pathogenic Berardinelli-Seip congenital lipodystrophy 2 variant (c.263A>G, p.Asn88Ser), confirming dHMN-V. Minipolymyoclonus of small amplitudes in bilateral wrists and ankles was an atypical presentation. This case underscores the importance of considering dHMN-V as a differential diagnosis in ALS-like distal upper extremity weakness.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy that mainly affects skeletal muscle. FSHD1 accounts for 95% of all FSHD cases and can be diagnosed based on the pathogenic contraction of the D4Z4-repeat array on chromosome 4q35. Genetic diagnosis of FSHD1 is challenging because of the large size and repetitive nature of the D4Z4 region. We evaluated the clinical applicability of optical genome mapping (OGM) for the genetic diagnosis of FSHD1. Methods: We included 25 individuals with clinically confirmed or suspected/probable FSHD and their families. Ultra-high-molecular-weight DNA from peripheral blood was labeled, stained, and imaged using a single-molecule OGM platform (Bionano Genomics Saphyr system). D4Z4 repeat size and haplotype information were analyzed using the manufacturer’s dedicated pipeline. We also compared the workflow and test time between Southern blot analysis and OGM. Results: We obtained concordant OGM and Southern blot results with 10 samples from patients with clinically confirmed FSHD. The D4Z4 repeat size differed within 1 unit between the Southern blot analysis and OGM. Among nine patients with clinically suspected or probable FSHD, six patients were confirmed to have pathogenic contractions by OGM.In our cohort, one de novo mosaic FSHD1 patient was successfully diagnosed with OGM.Moreover, OGM has a more straightforward and less time-consuming workflow than Southern blot analysis. Conclusions OGM enables accurate and reliable detection of pathogenic contraction of the D4Z4-repeat array and is a valuable tool for the genetic diagnosis of FSHD1.

Background: The three best-known NUP214 rearrangements found in leukemia (SET::NUP214, NUP214::ABL1, and DEK::NUP214) are associated with treatment resistance and poor prognosis. Mouse experiments have shown that NUP214 rearrangements alone are insufficient for leukemogenesis; therefore, the identification of concurrent mutations is important for accurate assessment and tailored patient management. Here, we characterized the demographic characteristics and concurrent mutations in patients harboring NUP214 rearrangements. Methods: To identify patients with NUP214 rearrangements, RNA-sequencing results of diagnostic bone marrow aspirates were retrospectively studied. Concurrent targeted nextgeneration sequencing results, patient demographics, karyotypes, and flow cytometry information were also reviewed. Results: In total, 11 patients harboring NUP214 rearrangements were identified, among whom four had SET::NUP214, three had DEK::NUP214, and four had NUP214::ABL1. All DEK::NUP214-positive patients were diagnosed as having AML. In patients carrying SET::NUP214 and NUP214::ABL1, T-lymphoblastic leukemia was the most common diagnosis (50%, 4/8). Concurrent gene mutations were found in all cases. PFH6 mutations were the most common (45.5%, 5/11), followed by WT1 (27.3%, 3/11), NOTCH1 (27.3%, 3/11), FLT3-internal tandem duplication (27.3%, 3/11), NRAS (18.2%, 2/11), and EZH2 (18.2%, 2/11) mutations. Two patients represented the second and third reported cases of NUP214::ABL1-positive AML. Conclusions We examined the characteristics and concurrent test results, including gene mutations, of 11 leukemia patients with NUP214 rearrangement. We hope that the elucidation of the context in which they occurred will aid future research on tailored monitoring and treatment.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy that mainly affects skeletal muscle. FSHD1 accounts for 95% of all FSHD cases and can be diagnosed based on the pathogenic contraction of the D4Z4-repeat array on chromosome 4q35. Genetic diagnosis of FSHD1 is challenging because of the large size and repetitive nature of the D4Z4 region. We evaluated the clinical applicability of optical genome mapping (OGM) for the genetic diagnosis of FSHD1. Methods: We included 25 individuals with clinically confirmed or suspected/probable FSHD and their families. Ultra-high-molecular-weight DNA from peripheral blood was labeled, stained, and imaged using a single-molecule OGM platform (Bionano Genomics Saphyr system). D4Z4 repeat size and haplotype information were analyzed using the manufacturer’s dedicated pipeline. We also compared the workflow and test time between Southern blot analysis and OGM. Results: We obtained concordant OGM and Southern blot results with 10 samples from patients with clinically confirmed FSHD. The D4Z4 repeat size differed within 1 unit between the Southern blot analysis and OGM. Among nine patients with clinically suspected or probable FSHD, six patients were confirmed to have pathogenic contractions by OGM.In our cohort, one de novo mosaic FSHD1 patient was successfully diagnosed with OGM.Moreover, OGM has a more straightforward and less time-consuming workflow than Southern blot analysis. Conclusions OGM enables accurate and reliable detection of pathogenic contraction of the D4Z4-repeat array and is a valuable tool for the genetic diagnosis of FSHD1.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy that mainly affects skeletal muscle. FSHD1 accounts for 95% of all FSHD cases and can be diagnosed based on the pathogenic contraction of the D4Z4-repeat array on chromosome 4q35. Genetic diagnosis of FSHD1 is challenging because of the large size and repetitive nature of the D4Z4 region. We evaluated the clinical applicability of optical genome mapping (OGM) for the genetic diagnosis of FSHD1. Methods: We included 25 individuals with clinically confirmed or suspected/probable FSHD and their families. Ultra-high-molecular-weight DNA from peripheral blood was labeled, stained, and imaged using a single-molecule OGM platform (Bionano Genomics Saphyr system). D4Z4 repeat size and haplotype information were analyzed using the manufacturer’s dedicated pipeline. We also compared the workflow and test time between Southern blot analysis and OGM. Results: We obtained concordant OGM and Southern blot results with 10 samples from patients with clinically confirmed FSHD. The D4Z4 repeat size differed within 1 unit between the Southern blot analysis and OGM. Among nine patients with clinically suspected or probable FSHD, six patients were confirmed to have pathogenic contractions by OGM.In our cohort, one de novo mosaic FSHD1 patient was successfully diagnosed with OGM.Moreover, OGM has a more straightforward and less time-consuming workflow than Southern blot analysis. Conclusions OGM enables accurate and reliable detection of pathogenic contraction of the D4Z4-repeat array and is a valuable tool for the genetic diagnosis of FSHD1.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is a common form of muscular dystrophy that mainly affects skeletal muscle. FSHD1 accounts for 95% of all FSHD cases and can be diagnosed based on the pathogenic contraction of the D4Z4-repeat array on chromosome 4q35. Genetic diagnosis of FSHD1 is challenging because of the large size and repetitive nature of the D4Z4 region. We evaluated the clinical applicability of optical genome mapping (OGM) for the genetic diagnosis of FSHD1. Methods: We included 25 individuals with clinically confirmed or suspected/probable FSHD and their families. Ultra-high-molecular-weight DNA from peripheral blood was labeled, stained, and imaged using a single-molecule OGM platform (Bionano Genomics Saphyr system). D4Z4 repeat size and haplotype information were analyzed using the manufacturer’s dedicated pipeline. We also compared the workflow and test time between Southern blot analysis and OGM. Results: We obtained concordant OGM and Southern blot results with 10 samples from patients with clinically confirmed FSHD. The D4Z4 repeat size differed within 1 unit between the Southern blot analysis and OGM. Among nine patients with clinically suspected or probable FSHD, six patients were confirmed to have pathogenic contractions by OGM.In our cohort, one de novo mosaic FSHD1 patient was successfully diagnosed with OGM.Moreover, OGM has a more straightforward and less time-consuming workflow than Southern blot analysis. Conclusions OGM enables accurate and reliable detection of pathogenic contraction of the D4Z4-repeat array and is a valuable tool for the genetic diagnosis of FSHD1.

Background: : A torn plantar plate (PP) is important pathologic anatomy related to a dislocated or subluxated metatarsophalangeal joint (MTPJ). Traditionally, a torn PP was treated with Weil osteotomy through a dorsal approach. However, because of the limited visualization of the dorsal approach, PP repair through a plantar approach has been proposed as a new technique. This study aimed to radiologically evaluate the outcome of PP repair through the plantar approach using an improved MTPJ overlap distance (MOD) on an anteroposterior view and the degree of subluxation on an oblique view. We also aimed to investigate the potential factors affecting the recurrence of MTPJ instability. Methods: In this study, we included 31 patients who had a subluxated or dislocated MTPJ of the second or third toe and underwent surgical PP repair. PP repair was performed via a plantar approach after shortening metatarsal (MT) osteotomy with a dorsal approach for longer MT bone. We assessed the severity of MTPJ subluxation by measuring the MOD and subluxation subtype on radiographs. Radiologic recurrence was defined as an increase in MOD or change from subluxation type A to subluxation type B.The relationship of recurrence with clinical and radiologic factors was evaluated by comparing the recurred group against the nonrecurred group. Results: Shortening MT osteotomy was performed in 26 of 31 cases (84%). Repeated measures analysis of variance comparing preoperation, pin removal, and the latest follow-up MOD values revealed the effectiveness of PP repair through the plantar approach (p < 0.001). The MOD did not significantly change after pin removal and the latest follow-up (p = 0.130), indicating that reduction was well maintained. None of the clinical and radiologic factors were significantly related to recurrence. However, 3 of 12 rheumatoid arthritis (RA) feet (25%) recurred and 3 of 5 recurred cases (60%) were RA feet. This result suggests that RA indicated a tendency for recurrence. Conclusions PP repair through the plantar approach has the advantage of excellent visualization of a torn PP and direct repair.We, therefore, recommend using the plantar approach for PP repair of the MTPJ.

Background: : A torn plantar plate (PP) is important pathologic anatomy related to a dislocated or subluxated metatarsophalangeal joint (MTPJ). Traditionally, a torn PP was treated with Weil osteotomy through a dorsal approach. However, because of the limited visualization of the dorsal approach, PP repair through a plantar approach has been proposed as a new technique. This study aimed to radiologically evaluate the outcome of PP repair through the plantar approach using an improved MTPJ overlap distance (MOD) on an anteroposterior view and the degree of subluxation on an oblique view. We also aimed to investigate the potential factors affecting the recurrence of MTPJ instability. Methods: In this study, we included 31 patients who had a subluxated or dislocated MTPJ of the second or third toe and underwent surgical PP repair. PP repair was performed via a plantar approach after shortening metatarsal (MT) osteotomy with a dorsal approach for longer MT bone. We assessed the severity of MTPJ subluxation by measuring the MOD and subluxation subtype on radiographs. Radiologic recurrence was defined as an increase in MOD or change from subluxation type A to subluxation type B.The relationship of recurrence with clinical and radiologic factors was evaluated by comparing the recurred group against the nonrecurred group. Results: Shortening MT osteotomy was performed in 26 of 31 cases (84%). Repeated measures analysis of variance comparing preoperation, pin removal, and the latest follow-up MOD values revealed the effectiveness of PP repair through the plantar approach (p < 0.001). The MOD did not significantly change after pin removal and the latest follow-up (p = 0.130), indicating that reduction was well maintained. None of the clinical and radiologic factors were significantly related to recurrence. However, 3 of 12 rheumatoid arthritis (RA) feet (25%) recurred and 3 of 5 recurred cases (60%) were RA feet. This result suggests that RA indicated a tendency for recurrence. Conclusions PP repair through the plantar approach has the advantage of excellent visualization of a torn PP and direct repair.We, therefore, recommend using the plantar approach for PP repair of the MTPJ.