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A previously unreported mutation in a Currarino syndrome kindred
Author(s) -
Wang Raymond Y.,
Jones Julie R.,
Chen Steve,
Rogers R. Curtis,
Friez Michael J.,
Schwartz Charles E.,
Graham John M.
Publication year - 2006
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.31420
Subject(s) - frameshift mutation , medicine , nonsense mutation , asymptomatic , missense mutation , imperforate anus , expressivity , phenotype , genetics , pathology , biology , gene , anatomy
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. © 2006 Wiley‐Liss, Inc.