Dona Aboud Syriani

<h3>Objective</h3> We evaluated the prevalence of pathogenic repeat expansions in replication factor C subunit 1 (<i>RFC1</i>) and disabled adaptor protein 1 <i>(DAB1)</i> in an undiagnosed ataxia cohort from North America. <h3>Methods</h3> A cohort of 596 predominantly adult-onset patients with undiagnosed familial or sporadic cerebellar ataxia was evaluated at a tertiary referral ataxia center and excluded for common genetic causes of cerebellar ataxia. Patients were then screened for the presence of pathogenic repeat expansions in <i>RFC1</i> (AAGGG) and <i>DAB1</i> (ATTTC) using fluorescent repeat-primed PCR (RP-PCR). Two additional undiagnosed ataxia cohorts from different centers, totaling 302 and 13 patients, respectively, were subsequently screened for <i>RFC1</i>, resulting in a combined 911 subjects tested. <h3>Results</h3> In the initial cohort, 41 samples were identified with 1 expanded allele in the <i>RFC1</i> gene (6.9%), and 9 had 2 expanded alleles (1.5%). For the additional cohorts, we found 20 heterozygous samples (6.6%) and 17 biallelic samples (5.6%) in the larger cohort and 1 heterozygous sample (7.7%) and 3 biallelic samples (23%) in the second. In total, 29 patients were identified with biallelic repeat expansions in <i>RFC1</i> (3.2%). Of these 29 patients, 8 (28%) had a clinical diagnosis of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), 14 had cerebellar ataxia with neuropathy (48%), 4 had pure cerebellar ataxia (14%), and 3 had spinocerebellar ataxia (10%). No patients were identified with expansions in the <i>DAB1</i> gene (spinocerebellar ataxia type 37). <h3>Conclusions</h3> In a large undiagnosed ataxia cohort from North America, biallelic pathogenic repeat expansion in <i>RFC1</i> was observed in 3.2%. Testing should be strongly considered in patients with ataxia, especially those with CANVAS or neuropathy.

Objective We evaluated the prevalence of pathogenic repeat expansions in replication factor C subunit 1 (RFC1) and disabled adaptor protein 1 (DAB1) in an undiagnosed ataxia cohort from North America. Methods A cohort of 596 predominantly adult-onset patients with undiagnosed familial or sporadic cerebellar ataxia was evaluated at a tertiary referral ataxia center and excluded for common genetic causes of cerebellar ataxia. Patients were then screened for the presence of pathogenic repeat expansions in RFC1 (AAGGG) and DAB1 (ATTTC) using fluorescent repeat-primed PCR (RP-PCR). Two additional undiagnosed ataxia cohorts from different centers, totaling 302 and 13 patients, respectively, were subsequently screened for RFC1, resulting in a combined 911 subjects tested. Results In the initial cohort, 41 samples were identified with 1 expanded allele in the RFC1 gene (6.9%), and 9 had 2 expanded alleles (1.5%). For the additional cohorts, we found 20 heterozygous samples (6.6%) and 17 biallelic samples (5.6%) in the larger cohort and 1 heterozygous sample (7.7%) and 3 biallelic samples (23%) in the second. In total, 29 patients were identified with biallelic repeat expansions in RFC1 (3.2%). Of these 29 patients, 8 (28%) had a clinical diagnosis of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), 14 had cerebellar ataxia with neuropathy (48%), 4 had pure cerebellar ataxia (14%), and 3 had spinocerebellar ataxia (10%). No patients were identified with expansions in the DAB1 gene (spinocerebellar ataxia type 37). Conclusions In a large undiagnosed ataxia cohort from North America, biallelic pathogenic repeat expansion in RFC1 was observed in 3.2%. Testing should be strongly considered in patients with ataxia, especially those with CANVAS or neuropathy.

PURPOSE: Percutaneous ultrasound-guided renal biopsy is essential for diagnosing medical renal disorders in transplant kidneys. A variety of techniques have been advocated. The purpose of this study is to evaluate the safety and efficacy of two different coaxial techniques and biopsy devices. METHODS: This single-center dual-arm, observation study cohort included 1831 consecutive transplant kidney biopsies performed over a 68-month period. Two coaxial techniques were used, distinguished by whether the 17 gauge (G) coaxial needle was advanced into the renal cortex (intracapsular technique; IC) or to the edge of the cortex (extracapsular technique; EC). One of two needle types could be used with either technique: an 18G side-cutting (Bard Max-Core or Mission) or an 18G end-cutting (Biopince Ultra) needle. In all cases, the cortical tangential technique was used to reduce the risk of central artery transgression and unnecessary medullary sampling. Patients were monitored for 30 days post-procedurally and complications were evaluated using the SIR adverse event classification. RESULTS: Of the 1831 patients included in the study cohort, 13 suffered severe bleeding complications requiring operative intervention. Of these patients, 8 underwent biopsy with side-cutting needle and IC, 2 with side-cutting needle and approach not specified, 2 with end-cutting needle and IC, and 1 with end-cutting needle and EC. There was no statistically significant difference in the risk of bleeding complications between different coaxial techniques and needle types. However, there was a significantly increased chance of inadequate sampling when comparing the side-cutting needle (1.0%) to the end-cutting needle (0.1%). CONCLUSIONS: Transplant kidney biopsy performed with two different coaxial techniques and needle types did not show differences in bleeding complications. There is an increased risk of inadequate sampling when using side-cutting relative to end-cutting biopsy devices.

We evaluated the prevalence of recently identified repeat-expansion disorders in an undiagnosed ataxia cohort from the United States.

ABSTRACT Objective Repeat expansions in RFC1 and DAB1 have recently been identified as causing cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) and spinocerebellar ataxia 37 (SCA37), respectively. We evaluated the prevalence of these repeat-expansions in an undiagnosed ataxia cohort from the United States. Methods A cohort of 596 patients with undiagnosed familial or sporadic cerebellar ataxia were evaluated at a tertiary referral ataxia center and excluded for common genetic causes of cerebellar ataxia. Patients were then screened for the presence of pathogenic repeat expansions in RFC1 (AAGGG) and DAB1 (ATTTC) using fluorescent repeat primed polymerase chain reaction (RP-PCR). Two additional undiagnosed ataxia cohorts from different centers, totaling 96 and 13 patients respectively, were subsequently screened for RFC1 resulting in a combined 705 subjects tested. Results In the initial cohort, 42 samples were identified with one expanded allele in the RFC1 gene (7.0%), and 9 had two expanded alleles (1.5%). For the additional cohorts, we found 12 heterozygous samples (12.5%) and 7 biallelic samples (7.3%) in the larger cohort, and 1 heterozygous sample (7.7%) and 3 biallelic samples (23%) in the second. In total, 19 patients were identified with biallelic repeat expansions in RFC1 (2.7%). Of these 19 patients, 6 (32%) had a clinical diagnosis of CANVAS, 10 had cerebellar ataxia with neuropathy (53%), and 3 had spinocerebellar ataxia (16%). No patients were identified with expansions in the DAB1 gene. Conclusion In a large undiagnosed ataxia cohort from the United States, biallelic pathogenic repeat expansion in RFC1 was observed in 2.7%. Testing should be strongly considered in ataxia patients, especially those with CANVAS or neuropathy.