FAM111B Mutation Is Associated With Inherited Exocrine Pancreatic Dysfunction.
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.



Whole exome sequencing was performed to identify the genetic cause of exocrine pancreatic dysfunction.



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.



Our findings implicate FAM111B in autosomal dominantly inheritable exocrine pancreatic dysfunction.
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.
Aaron
A
Seo
Tom
T
Walsh
Ming K
MK
Lee
Phoenix A
PA
Ho
Evelyn Kanyu
EK
Hsu
Robert
R
Sidbury
Mary-Claire
MC
King
Akiko
A
Shimamura
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D059472:Exome / Q000235:genetics; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D046790:Pancreas, Exocrine / Q000378:metabolism* / Q000503:physiopathology; D010182:Pancreatic Diseases / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA / Q000379:methods; D012689:Sequence Homology, Nucleic Acid; D035781:Siblings
D018797:Cell Cycle Proteins; C586301:FAM111B protein, human