[SMARCAL1 gene analysis of 2 Chinese Schimke immuno-osseous dysplasia children].
OBJECTIVE
Schimke immuno-osseous dysplasia (SIOD), is an autosomal recessive inherited disease caused by SMARCAL1 (MIM:20606622) mutations, while in about half of the patients no any mutation in SMARCAL1 could be found. This disease involves multiple systems and is characterized by short and dissymmetric stature with spondyloepiphyseal dysplasia, progressive renal failure, lymphopenia with recurrent infections, and hyperpigmented macules. This study aimed to analyze SMARCAL1 gene of 2 unrelated suspected SIOD children, to make definite diagnosis, and find more SMARCAL1 mutation types of Chinese SIOD.


METHODS
Two suspected Chinese Han male SIOD children who visited our hospital from 2008 to 2014, aged 3 y 6 m and 7 y 8 m, both were short and had spondyloepiphyseal dysplasia, progressive renal failure, lymphopenia with recurrent infections. After informed consent, they and their parents's DNA were extracted from blood. PCRs for all 16 exons of SMARCAL1 were performed and PCR products were purified by 2% gel electrophoresis and sequenced directly. Pathogenicity of missense variations was confirmed by SIFT and sequencing SMARCAL1 of fifty normal controls.


RESULTS
(1) Four gene variations were found in the two children: Two reported missense mutations c.1129G>C, p.Glu377Gln and c.1933C>T, p. Arg645Cys. Two splicing mutations c.1334+1G>A and c.2142-1 G>A were detected. (2) c.1129G>C, p.Glu377Gln were reported as a disease-causing mutations before, but it was an single nucleotide polymorphism (SNP) which was found in 15 of 50 normal controls. (3) Two novel splicing mutations were found in this study: c.1334+1G>A and c.2142-1 G>A.


CONCLUSIONS
(1) We detected 3 disease-causing mutations in 2 SIOD children by SMARCAL1 gene analysis, while 2 splicing mutations were novel mutations. (2) c.1129G>C, p.Glu377Gln was a SNP but not a disease-causing mutation at least in Chinese population.
Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Wei
W
Wang
Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China. Email: songhm1021@hotmail.com.
Hongmei
H
Song
Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Min
M
Wei
Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Zhengqing
Z
Qiu
Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Chen
C
Wang
Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Yu
Y
Zhang
Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Ming
M
Li
Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Yuheng
Y
Yuan
Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Xiaoyan
X
Tang
D001161:Arteriosclerosis / Q000150:complications / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004265:DNA Helicases / Q000235:genetics*; D005091:Exons; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000235:genetics*; D008231:Lymphopenia; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D009404:Nephrotic Syndrome / Q000150:complications / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000150:complications / Q000151:congenital / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000081207:Primary Immunodeficiency Diseases; D011655:Pulmonary Embolism / Q000150:complications / Q000235:genetics*; D051437:Renal Insufficiency
C412482:SMARCAL1 protein, human; D004265:DNA Helicases