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The historical Coffin–Lowry syndrome family revisited: Identification of two novel mutations of RPS6KA3 in three male patients
Author(s) -
Nishimoto Hiromi Koso,
Ha Kyungsoo,
Jones Julie R.,
Dwivedi Alka,
Cho HyunMin,
Layman Lawrence C.,
Kim HyungGoo
Publication year - 2014
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.36488
Subject(s) - missense mutation , exon , genetics , hypotonia , cls upper limits , biology , mutation , medicine , gene , optometry
Coffin–Lowry syndrome (CLS) is a rare X‐linked dominant disorder characterized by intellectual disability, craniofacial abnormalities, short stature, tapering fingers, hypotonia, and skeletal malformations. CLS is caused by mutations in the Ribosomal Protein S6 Kinase, 90 kDa, Polypeptide 3 ( RPS6KA3 ) gene located at Xp22.12, which encodes Ribosomal S6 Kinase 2 (RSK2). Here we analyzed RPS6KA3 in three unrelated CLS patients including one from the historical Coffin–Lowry syndrome family and found two novel mutations. To date, over 140 mutations in RPS6KA3 have been reported. However, the etiology of the very first familial case, which was described in 1971 by Lowry with detailed phenotype and coined the term CLS, has remained unknown. More than 40 years after the report, we succeeded in identifying deposited fibroblast cells from one patient of this historic family and found a novel heterozygous 216 bp in‐frame deletion, encompassing exons 15 and 16 of RPS6KA3 . Drop episodes in CLS patients were reported to be associated with truncating mutations deleting the C‐terminal kinase domain (KD), and only one missense mutation and one single basepair duplication involving the C‐terminal KD of RSK2 in the patients with drop episode have been reported thus far. Here we report the first in‐frame deletion in C‐terminal KD of RPS6KA3 in a CLS patient with drop episodes. © 2014 Wiley Periodicals, Inc.