Expanding the phenotypic spectrum of ARCN1-related syndrome

Ritter, Alyssa; Gold, Jessica I.; Hayashi, Hiroshi; Ackermann, Amanda M.; Hanke, Stephanie; Skraban, Cara; Cuddapah, Sanmati; Bhoj, Elizabeth; Liu, Dong; Kuroda, Yukiko; Wen, Jessica; Takeda, Ryojun; Bibb, Audrey L.; Chehadeh, Salima El; Piton, Amélie; Ohl, J.; Kukolich, Mary K.; Nagasaki, Keisuke; Kato, Kohji; Ogi, Tomoo; Russo, Pierre; Krock, Bryan L.; Murrell, Jill R.; Sullivan, Jennifer; Shashi, Vandana; Stong, Nicholas; Hákonarson, Hákon; Sawano, Kentaro; Torti, Erin; Willaert, Rebecca; Si, Yue; Wilcox, William R.; Wirgenes, Katrine Verena; Thomassen, Kristian; Carlotti, Katherine; Erwin, Angelika; Lazier, Joanna; Marquardt, Thorsten; He, Miao; Edmondson, Andrew C.; Izumi, Kosuke

doi:10.1016/j.gim.2022.02.005

Cited by 5 publications

(8 citation statements)

References 14 publications

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“…Data from this study have been included in 32 publications, including novel gene‐disease associations, 38–46 novel phenotypes 24–28 and phenotype expansions 29–37 for ultra‐rare disorders.…”

Section: Resultsmentioning

confidence: 99%

“…Most of the 138 definite/likely diagnoses were known disorders (n = 115, 83%); the remaining were new phenotypes for genes previously known to be associated with disease (n = 5, 3.6%) [24][25][26][27][28] and phenotypic expansions for known disorders (n = 9, 6.5%). [29][30][31][32][33][34][35][36][37] Additionally, nine new gene-disease associations (6.5% of the def/likely diagnoses) were established. [38][39][40][41][42][43][44][45][46]…”

Section: Types Of Diagnosesmentioning

confidence: 99%

“…Data from this study have been included in 32 publications, including novel gene-disease associations, [38][39][40][41][42][43][44][45][46] novel phenotypes [24][25][26][27][28] and phenotype expansions [29][30][31][32][33][34][35][36][37] for ultra-rare disorders. For the fourth patient, the UDN prioritized a homozygous missense variant in a gene that had in the interim been associated with a disease.…”

Section: Academic Impactmentioning

confidence: 99%

See 2 more Smart Citations

The best of both worlds: Blending cutting‐edge research with clinical processes for a productive exome clinic

Sullivan,

Spillmann,

Schoch

et al. 2023

Clinical Genetics

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Genomic medicine has been transformed by next‐generation sequencing (NGS), inclusive of exome sequencing (ES) and genome sequencing (GS). Currently, ES is offered widely in clinical settings, with a less prevalent alternative model consisting of hybrid programs that incorporate research ES along with clinical patient workflows. We were among the earliest to implement a hybrid ES clinic, have provided diagnoses to 45% of probands, and have identified several novel candidate genes. Our program is enabled by a cost‐effective investment by the health system and is unique in encompassing all the processes that have been variably included in other hybrid/clinical programs. These include careful patient selection, utilization of a phenotype‐agnostic bioinformatics pipeline followed by manual curation of variants and phenotype integration by clinicians, close collaborations between the clinicians and the bioinformatician, pursuit of interesting variants, communication of results to patients in categories that are predicated upon the certainty of a diagnosis, and tracking changes in results over time and the underlying mechanisms for such changes. Due to its effectiveness, scalability to GS and its resource efficiency, specific elements of our paradigm can be incorporated into existing clinical settings, or the entire hybrid model can be implemented within health systems that have genomic medicine programs, to provide NGS in a scientifically rigorous, yet pragmatic setting.

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Section: Resultsmentioning

confidence: 99%

Section: Types Of Diagnosesmentioning

confidence: 99%

Section: Academic Impactmentioning

confidence: 99%

See 1 more Smart Citation

The best of both worlds: Blending cutting‐edge research with clinical processes for a productive exome clinic

Sullivan,

Spillmann,

Schoch

et al. 2023

Clinical Genetics

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“…The phenotypic spectrum of ARCN1-related syndrome has been described in 15 patients and 5 fetal cases in the past 6 years. [1][2][3][4] Core features include fetal growth restriction and micrognathia, and other common features are genitourinary anomalies, microcephaly and developmental delay. In contrast to liveborn cases, fetal cases more often have rhizomelic shortening and skeletal anomalies.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to liveborn cases, fetal cases more often have rhizomelic shortening and skeletal anomalies. 4 ARCN1 encodes the coatomer subunit delta of coat protein complex I (COPI), which is essential for intracellular transport of type 1 collagen. 1 Another example of deficient COPI transport of collagen is due to mutations in KDELR2 and shows a severe osteogenesis imperfecta (OI) phenotype.…”

Section: Introductionmentioning

confidence: 99%

The Radiological and Histological Phenotype of Skeletal Abnormalities in Fetal ARCN1-Related Syndrome

Houck,

Koopmans,

Nikkels

2023

Pediatr Dev Pathol

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Mutations in ARCN1 give rise to a syndromic disorder with rhizomelic short stature with microretrognathia and developmental delay. ARCN1 encodes the delta subunit of the coat protein I complex, which is required for intracellular trafficking of collagen 1 and which may also be involved in the endoplasmic reticulum (ER) stress response. In this paper we describe for the first time the skeletal histological abnormalities in an 18-week-old fetus with an ARCN1 mutation, and we suggest that the skeletal phenotype in ARCN1-related syndrome has more resemblance with ER stress than with a defect in collagen 1 metabolism.

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SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis

Tobias,

Lucas-Herald,

Sagar

et al. 2024

Endocrine

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Expanding the phenotypic spectrum of ARCN1-related syndrome

Cited by 5 publications

References 14 publications

The best of both worlds: Blending cutting‐edge research with clinical processes for a productive exome clinic

The best of both worlds: Blending cutting‐edge research with clinical processes for a productive exome clinic

The Radiological and Histological Phenotype of Skeletal Abnormalities in Fetal ARCN1-Related Syndrome

SEC31A may be associated with pituitary hormone deficiency and gonadal dysgenesis

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