Aaron Seo1, Tom Walsh, Ming K Lee, Phoenix A Ho, Evelyn Kanyu Hsu, Robert Sidbury, Mary-Claire King, Akiko Shimamura. 1. From the *Department of Genome Sciences, University of Washington; †Clinical Research Division, Fred Hutchinson Cancer Research Center; ‡Division of Medical Genetics, University of Washington; §Pediatric Hematology/Oncology, Seattle Children's Hospital; ∥Department of Pediatrics, University of Washington; ¶Pediatric Gastroenterology and Hepatology, and #Department of Dermatology, Seattle Children's Hospital, Seattle, WA; and **Boston Children's Hospital, Dana Farber Cancer Institute, and Harvard Medical School, Boston, MA.
Abstract
OBJECTIVES: Few genetic causes of exocrine pancreatic dysfunction have been described to date. We identified a family with multiple affected members manifesting exocrine pancreatic dysfunction. Additional associated features included facial rash, sparse hair, hypohidrosis, and swelling of the extremities. The transmission pattern of these clinical features was consistent with an autosomal dominant mode of inheritance. The 2 proband siblings also had transient elevated liver transaminases with hepatic steatosis early in life. This study identifies the genetic cause of exocrine pancreatic dysfunction in this family. METHODS: Whole exome sequencing was performed to identify the genetic cause of exocrine pancreatic dysfunction. RESULTS: A heterozygous germline in-frame deletion in the gene FAM111B (c.1261_1263delAAG, p.Lys421del) cosegregated with the phenotype: the variant was present in all affected relatives genotyped and absent in all unaffected relatives genotyped. The variant is also absent from public control sequence databases. CONCLUSIONS: Our findings implicate FAM111B in autosomal dominantly inheritable exocrine pancreatic dysfunction.
OBJECTIVES: Few genetic causes of exocrine pancreatic dysfunction have been described to date. We identified a family with multiple affected members manifesting exocrine pancreatic dysfunction. Additional associated features included facial rash, sparse hair, hypohidrosis, and swelling of the extremities. The transmission pattern of these clinical features was consistent with an autosomal dominant mode of inheritance. The 2 proband siblings also had transient elevated liver transaminases with hepatic steatosis early in life. This study identifies the genetic cause of exocrine pancreatic dysfunction in this family. METHODS: Whole exome sequencing was performed to identify the genetic cause of exocrine pancreatic dysfunction. RESULTS: A heterozygous germline in-frame deletion in the gene FAM111B (c.1261_1263delAAG, p.Lys421del) cosegregated with the phenotype: the variant was present in all affected relatives genotyped and absent in all unaffected relatives genotyped. The variant is also absent from public control sequence databases. CONCLUSIONS: Our findings implicate FAM111B in autosomal dominantly inheritable exocrine pancreatic dysfunction.
Authors: Graeme R B Boocock; Jodi A Morrison; Maja Popovic; Nicole Richards; Lynda Ellis; Peter R Durie; Johanna M Rommens Journal: Nat Genet Date: 2002-12-23 Impact factor: 38.330
Authors: Michael Y Zhang; Siobán B Keel; Tom Walsh; Ming K Lee; Suleyman Gulsuner; Amanda C Watts; Colin C Pritchard; Stephen J Salipante; Michael R Jeng; Inga Hofmann; David A Williams; Mark D Fleming; Janis L Abkowitz; Mary-Claire King; Akiko Shimamura Journal: Haematologica Date: 2014-09-19 Impact factor: 9.941
Authors: J R Riordan; J M Rommens; B Kerem; N Alon; R Rozmahel; Z Grzelczak; J Zielenski; S Lok; N Plavsic; J L Chou Journal: Science Date: 1989-09-08 Impact factor: 47.728
Authors: J M Rommens; M C Iannuzzi; B Kerem; M L Drumm; G Melmer; M Dean; R Rozmahel; J L Cole; D Kennedy; N Hidaka Journal: Science Date: 1989-09-08 Impact factor: 47.728
Authors: Wan F Ip; Annie Dupuis; Lynda Ellis; Satti Beharry; Jodi Morrison; Michael O Stormon; Mary Corey; Johanna M Rommens; Peter R Durie Journal: J Pediatr Date: 2002-08 Impact factor: 4.406
Authors: Marina Macchiaiolo; Filippo M Panfili; Davide Vecchio; Fabiana Cortellessa; Michaela V Gonfiantini; Paola S Buonuomo; Andrea Pietrobattista; Paola Francalanci; Lorena Travaglini; Enrico S Bertini; Maya El Hachem; Andrea Bartuli Journal: Am J Med Genet A Date: 2022-07-23 Impact factor: 2.578