An unusual phenotype of X‐linked developmental delay and extreme behavioral difficulties associated with a mutation in the EBP gene. Issue 4 (23rd January 2014)

• Record Type: Journal Article
• Authors: Hartill, Verity L.; Tysoe, Carolyn; Manning, Nigel; Dobbie, Angus; Santra, Saikat; Walter, John; Caswell, Richard; Koster, Janet; Waterham, Hans; Hobson, Emma
• Is Part Of: American journal of medical genetics. Volume 164:Issue 4(2014.)
• Page Start: 907
• Page End: 914
• Publication Date: 2014-01-23
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36368
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga36368-sec-0001" sec-type="section"> <p>We report on a family in which four males over three generations are affected with X‐linked recessive developmental delay, learning difficulties, severe behavioral difficulties and mild dysmorphic features. Plasma sterol analysis in three of the four affected males demonstrated increased concentrations of 8‐dehydrocholesterol (8‐DHC) and cholest‐8(9)‐enol. All four affected males had a novel hemizygous missense mutation, p.W47R (c.139T>C), in <italic>EBP</italic>. Functional studies showed raised levels of cholest‐8(9)‐enol in patient's cultured fibroblast cells, which were suppressed when the cells were incubated with simvastatin. <italic>EBP</italic> encodes 3β‐hydroxysteroid‐delta8, delta7‐isomerase, a key enzyme involved in the cholesterol biosynthesis pathway. Mutations in <italic>EBP</italic> have previously been associated with Conradi–Hunermann–Happle syndrome (CHH), an X‐linked dominant disorder characterized by skeletal dysplasia, skin, and ocular abnormalities, which is usually lethal in males. Four previous reports describe X‐linked recessive multiple anomaly syndromes associated with non‐mosaic <italic>EBP</italic> mutations in males, two at the same amino acid position, p.W47C. This phenotype has previously been described as "MEND" syndrome (male <italic>EBP</italic> disorder with neurological defects). The family reported herein represent either a novel phenotype, or an expansion of the MEND phenotype, characterized by extreme behavioral difficulties and a scarcity of structural anomalies. Simvastatin therapy is being evaluated in two males from this family. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>