Screening for AIP gene mutations in a Han Chinese pituitary adenoma cohort followed by LOH analysis.
OBJECTIVE
The aryl hydrocarbon receptor interacting protein gene (AIP) is associated with pituitary adenoma (PA). AIP has not been sequenced in East Asian PA populations, so we performed this study in a Han Chinese cohort.


METHODS
Our study included six familial PA pedigrees comprising 16 patients and 27 unaffected relatives, as well as 216 sporadic PA (SPA) patients and 100 unrelated healthy controls.


METHODS
AIP sequencing was carried out on genomic DNA isolated from blood samples. Multiplex ligation-dependent probe amplification and microsatellite marker analyses on DNA from the paired tumor tissues were performed for loss of heterozygosity analysis.


RESULTS
We identified three common and four rare single nucleotide polymorphisms (SNPs), one intron insertion, one novel synonymous variant, four novel missense variants, and a reported nonsense mutation in three familial isolated PA (FIPA) cases from the same family. Large genetic deletions were not observed in the germline but were seen in the sporadic tumor DNA from three missense variant carriers. The prevalence of AIP pathogenic variants in PA patients here was low (3.88%), but was higher in somatotropinoma patients (9.30%), especially in young adults (≤30 years) and pediatric (≥18 years) paients (17.24% and 25.00% respectively). All AIP variant patients suffered from macroadenomas. However, the AIP mutation rate in FIPA families was low in this cohort (16.67%, 1/6 families).


CONCLUSIONS
AIP gene mutation may not be frequent in FIPA or SPA from the Han Chinese population. AIP sequencing and long-term follow-up investigations should be performed for young patients with large PAs and their families with PA predisposition.
Department of Neurosurgery, Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing 100730, People's Republic of China.
Feng
F
Cai
Yi-Dan
YD
Zhang
Xiuli
X
Zhao
Ya-Kun
YK
Yang
Si-Hai
SH
Ma
Cong-Xin
CX
Dai
Xiao-Hai
XH
Liu
Yong
Y
Yao
Ming
M
Feng
Jun-Ji
JJ
Wei
Bing
B
Xing
Yong-Hui
YH
Jiao
Zhen-Qing
ZQ
Wei
Zhen-Ming
ZM
Yin
Bo
B
Zhang
Feng
F
Gu
Ren-Zhi
RZ
Wang
D000236:Adenoma / Q000453:epidemiology / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D002648:Child; D002681:China / Q000453:epidemiology; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D016254:Mutagenesis, Insertional; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D010911:Pituitary Neoplasms / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
D047908:Intracellular Signaling Peptides and Proteins; C103265:aryl hydrocarbon receptor-interacting protein