Unusual presentation of familial glucocorticoid deficiency with a novel MRAP mutation.
BACKGROUND
Mutations in MRAP, an interacting partner of the ACTH receptor, have been shown recently to cause familial glucocorticoid deficiency (FGD) in kindreds with confirmed FGD and no ACTH receptor mutations.


OBJECTIVE
We describe a Jewish-Ethiopian family with FGD caused by a novel MRAP mutation.


METHODS
Our index patient presented at the age of 19 months with hypocortisolism, severe psychomotor retardation, myoclonic seizures, spastic quadriparesis, and microcephaly. Before the definite diagnosis was made, a female sibling was born in another hospital and succumbed during the neonatal period due to sepsis and adrenal crisis.


METHODS
DNA was extracted from peripheral blood samples from the index case and his mother and from fibroblasts obtained from the female patient. The DAX-1, ACTH receptor (MC2R), and MRAP genes were analyzed.


RESULTS
The index patient was diagnosed with FGD and was found to be homozygous for a novel MRAP mutation, a seven-base deletion in exon 3 of the MRAP gene. This deletion causes a frame shift, resulting in a stop codon after 23 amino acids (L31X). Postmortem analysis of fibroblasts obtained from the female patient revealed that she harbored the same mutation.


CONCLUSIONS
This is the first report of MRAP mutations after the recent identification of the gene. Whether the novel MRAP mutation described by us is associated with a particularly severe phenotype remains to be investigated.
Modan-Moses
Dalit
D
Pediatric Endocrinology Unit, Division of Pediatrics, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel. dmodan@sheba.health.gov.il
Ben-Zeev
Bruria
B
Hoffmann
Chen
C
Falik-Zaccai
Tzipora C
TC
Bental
Yoram A
YA
Pinhas-Hamiel
Orit
O
Anikster
Yair
Y
D004831:Epilepsies, Myoclonic / Q000209:etiology; D005938:Glucocorticoids / Q000172:deficiency*; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000209:etiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008831:Microcephaly / Q000209:etiology; D009154:Mutation; D011782:Quadriplegia / Q000209:etiology; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics
D005938:Glucocorticoids; C458099:MRAP protein, human; D008565:Membrane Proteins; D044103:Receptor, Melanocortin, Type 2