Send to

Choose Destination
Cold Spring Harb Mol Case Stud. 2018 Oct 1;4(5). pii: a003046. doi: 10.1101/mcs.a003046. Print 2018 Oct.

Further evidence for the involvement of EFL1 in a Shwachman-Diamond-like syndrome and expansion of the phenotypic features.

Collaborators (199)

Alejandro ME, Azamian MS, Bacino CA, Balasubramanyam A, Bostwick BL, Burrage LC, Chen S, Clark GD, Craigen WJ, Dhar SU, Emrick LT, Goldman AM, Hanchard NA, Jamal F, Karaviti L, Lalani SR, Lee BH, Lewis RA, Marom R, Moretti PM, Murdock DR, Nicholas SK, Orange JS, Orengo JP, Posey JE, Potocki L, Rosenfeld JA, Samson SL, Scott DA, Tran AA, Vogel TP, Bellen HJ, Wangler MF, Yamamoto S, Eng CM, Muzny DM, Ward PA, Yang Y, Goldstein DB, Stong N, Cope H, Jiang YH, McConkie-Rosell A, Pena LDM, Schoch K, Shashi V, Spillmann RC, Sullivan JA, Tan QK, Walley NM, Aaron A, Beggs AH, Berry GT, Briere LC, Cooper CM, Donnell-Fink LA, Fieg EL, High F, Korrick S, Krier JB, Lincoln SA, Loscalzo J, Maas RL, MacRae CA, Carl Pallais J, Rodan LH, Silverman EK, Stoler JM, Sweetser DA, Walker M, Walsh CA, Esteves C, Glanton E, Holm IA, Kohane IS, McCray AT, Might M, LeBlanc K, Bick DP, Birch CL, Boone BE, Brown DM, Dorset DC, Jones AL, Lazar J, Levy SE, May T, Scott Newberry J, Worthey EA, Batzli GF, Colley HA, Dayal JG, Eckstein DJ, Gould SE, Howerton EM, Krasnewich DM, Mamounas LA, Manolio TA, Mulvihill JJ, Urv TK, Wise AL, Brush M, Gourdine JF, Haendel M, Koeller DM, Kyle JE, Metz TO, Waters KM, Webb-Robertson BM, Ashley EA, Bernstein JA, Bonner D, Coakley TR, Davidson JM, Dries AM, Enns GM, Fernandez L, Fisher PG, Friedman ND, Hom J, Huang Y, Kohler JN, Majcherska MM, Marwaha S, McCormack CE, Merker JD, Reuter CM, Sampson JB, Smith KS, Waggott DM, Wheeler MT, Zastrow DB, Zhao C, Allard P, Barseghyan H, Butte MJ, Dell'Angelica EC, Dipple KM, Dorrani N, Douine ED, Eskin A, Fogel BL, Lee H, Loo SK, Martin MG, Martínez-Agosto JA, Nelson SF, Palmer CG, Papp JC, Parker NH, Signer R, Sinsheimer JS, Vilain E, Wan J, Yoon AJ, Zheng A, Behnam B, Burke EA, D'Souza P, Davids M, Draper DD, Estwick T, Ferreira C, Godfrey RA, Groden CA, Johnston JM, Christopher Lau C, Macnamara EF, Maduro VV, Markello TC, Morimoto M, Murphy JL, Nehrebecky ME, Novacic D, Pusey BN, Sharma P, Wahl CE, Yu G, Gropman AL, Baker E, Adams DR, Gahl WA, Malicdan MCV, Tifft CJ, Wolfe LA, Yang J, Postlethwait JH, Westerfield M, Bican A, Brokamp E, Duncan L, Hamid R, Kozuira M, Newman JH, Phillips JA 3rd, Rives L, Robertson AK, Shakachite L, Cogan JD.

Author information

Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.
Institute for Genomic Medicine, Columbia University, New York, New York 10032, USA.
Department of Pediatrics, Division of Hematology-Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Duke University Medical Center, Durham, North Carolina 27710, USA.
Department of Radiology, Division of Pediatric Radiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Cedars-Sinai Medical Center, International Skeletal Dysplasia Registry, Los Angeles, California 90048, USA.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Department of Psychiatry and Behavioral Sciences, Division of Child and Family Mental Health and Developmental Neuroscience, Duke University Medical Center, Durham, North Carolina 27710, USA.
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Cincinnati Children's Hospital Medical Center, Division of Human Genetics, Cincinnati, Ohio 45229, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Contributed equally


Recent evidence has implicated EFL1 in a phenotype overlapping Shwachman-Diamond syndrome (SDS), with the functional interplay between EFL1 and the previously known causative gene SBDS accounting for the similarity in clinical features. Relatively little is known about the phenotypes associated with pathogenic variants in the EFL1 gene, but the initial indication was that phenotypes may be more severe, when compared with SDS. We report a pediatric patient who presented with a metaphyseal dysplasia and was found to have biallelic variants in EFL1 on reanalysis of trio whole-exome sequencing data. The variant had not been initially reported because of the research laboratory's focus on de novo variants. Subsequent phenotyping revealed variability in her manifestations. Although her metaphyseal abnormalities were more severe than in the original reported cohort with EFL1 variants, the bone marrow abnormalities were generally mild, and there was equivocal evidence for pancreatic insufficiency. Despite the limited number of reported patients, variants in EFL1 appear to cause a broader spectrum of symptoms that overlap with those seen in SDS. Our report adds to the evidence of EFL1 being associated with an SDS-like phenotype and provides information adding to our understanding of the phenotypic variability of this disorder. Our report also highlights the value of exome data reanalysis when a diagnosis is not initially apparent.


congenital thrombocytopenia; exocrine pancreatic insufficiency; hepatic bridging fibrosis; hypercalciuria; intellectual disability, mild; portal fibrosis; short stature; spondylometaphyseal dysplasia

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center