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Non‐syndromic X‐linked mental retardation associated with a missense mutation (P312L) in the FGD1 gene
Author(s) -
Lebel RR,
May M,
Pouls S,
Lubs HA,
Stevenson RE,
Schwartz CE
Publication year - 2002
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1034/j.1399-0004.2002.610209.x
Subject(s) - missense mutation , genetics , mutation , exon , biology , craniofacial , short stature , noonan syndrome , gene , endocrinology
Three brothers with non‐syndromal X‐linked mental retardation were found to have a novel missense mutation in FGD1, the gene associated with the Aarskog syndrome. Although the brothers have short stature and small feet, they lack distinct craniofacial, skeletal or genital findings suggestive of Aarskog syndrome. Their mother, the only obligate carrier available for testing, has the FGD1 mutation. The mutation, a C934T base change in exon 4, results in the proline at position 312 to be substituted with a leucine. This missense mutation is predicted to eliminate a β‐turn, creating an extra‐long stretch of coiled sequence which may affect the orientations of an SH3 (Src homology 3) binding domain and the first structural conserved region. A new molecular defect associated with non‐syndromal X‐linked mental retardation affords an opportunity to seek specific diagnosis in males with previously unexplained developmental delays and this opens further predictive tests in families at risk.