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A novel X‐linked multiple congenital anomaly syndrome associated with an EBP mutation
Author(s) -
Furtado Larissa V.,
BayrakToydemir Pinar,
Hulinsky Becki,
Damjanovich Kristy,
Carey John C.,
Rope Alan F.
Publication year - 2010
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.33674
Subject(s) - missense mutation , biology , agenesis of the corpus callosum , genetics , phenotype , endocrinology , mutation , craniofacial , medicine , cataracts , dysplasia , gene , corpus callosum , anatomy
Mutations of the gene coding for emopamil binding protein (EBP) can lead to deficient activity of 3‐β‐hydroxysteroid Δ 8 , Δ 7 isomerase and are most commonly identified in. association with the X‐linked dominant (male lethal) chondrodysplasia punctata (CDPX2), also known as Conradi‐Hunermann syndrome. Our group has identified a hemizygous EBP mutation in males with a phenotype remarkable for Dandy‐Walker malformation, cataracts, collodion skin and cryptorchidism. Additional findings of hydrocephalus, dysplasia of the corpus callosum, cardiovascular, craniofacial and skeletal anomalies were regularly seen in affected males and the family histories were supportive of an X‐linked ‐recessive condition. The regularly reproducible constellation of cardinal features aligns very nicely with other disorders of sterol biosynthesis and is further distinguished by an absence of arty clinical manifestations in obligate carrier females. Biochemical analysis of blood from cases demonstrated markedly increased levels of 8(9)‐cholestenol, and 8‐dehydroeholesterol and a mildly increased level of 7‐dehydrocholesterol; a similar pattern to what is seen in CDPX2. Sequence analysis of EJJP revealed a novel hemizygous missense mutation at position 141, predictive of a tryptophan to cysteine substitution (c.141G>T, p.W47C). The unaffected mothers were heterozygous for the c.141G>T mutation arid showed random X‐inactivation pattern upon. © 2010 Wiley‐Liss, Inc.