title: A previously unreported mutation in a Currarino syndrome kindred.
abstract: Currarino syndrome consists of autosomal dominant hereditary sacral dysgenesis that is caused by mutations of the HOX gene, HLXB9. Sacral malformation, presacral mass, and anorectal malformations comprise the classic triad, but other common symptoms and malformations include neonatal-onset bowel obstruction, chronic constipation, recurrent perianal sepsis, renal/urinary tract anomalies, female internal genital anomalies, tethered spinal cord, and anterior meningocele. Up to 33% of patients are asymptomatic. There is marked inter- and intrafamilial variability in expression, and no genotype/phenotype correlations have been identified. To date, 32 different mutations have been identified in HLXB9: all nine missense mutations were found in the homeodomain, while the others were nonsense, frameshift, splice site mutations, or heterozygous whole-gene deletions. We report a four-generation family with Currarino syndrome varying in severity from very mild to full expression of the Currarino triad. They were found to carry a previously unreported nonsense mutation, E283X, absent in tested asymptomatic first-degree relatives. This family provides additional information on the degree of intrafamilial variability associated with HLXB9 mutations.
authors.affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, California 90048, USA. Raymond.wang@schs.org
authors.forename: Raymond Y
authors.initials: RY
authors.lastname: Wang
authors.forename: Julie R
authors.initials: JR
authors.lastname: Jones
authors.forename: Steve
authors.initials: S
authors.lastname: Chen
authors.forename: R Curtis
authors.initials: RC
authors.lastname: Rogers
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Friez
authors.forename: Charles E
authors.initials: CE
authors.lastname: Schwartz
authors.forename: John M
authors.initials: JM
authors.lastname: Graham
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001003:Anal Canal / Q000002:abnormalities* / Q000000981:diagnostic imaging; D002648:Child; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D011859:Radiography; D012007:Rectum / Q000002:abnormalities* / Q000000981:diagnostic imaging; D012447:Sacrum / Q000002:abnormalities* / Q000000981:diagnostic imaging; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C490003:MNX1 protein, human; D014157:Transcription Factors