Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene Mutations in Acromegaly
Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene Mutations in Acromegaly
Acromegaly is a rare disease caused by growth hormone (GH) secreting pituitary adenoma in
 more than 95% of cases. Acromegaly can be seen sporadically or may be associated with a
 variety of genetic syndromes such as Multiple Endocrine Neoplasia Type 1, Carney Complex,
 familial isolated pituitary adenoma (FIPA) and Mc-Cune Albright Syndrome. The accompanying
 features of these syndromes and family history are helpful in the differential diagnosis.
 Aryl hydrocarbon receptor (AHR)-interacting protein (AIP) gene mutations can be seen
 sporadically as well as in FIPA. But the prescience of the presence of AIP mutation is
 limited by positive family history and early-onset of acromegaly. Furthermore, the
 probability of the patient to be the index case of the family should not be ignored.

 Screening for AIP gene mutation is recommended in patients with pituitary adenomas of
 childhood-onset, GH or prolactin secreting tumors who are diagnosed before the age of 30
 years and positive family history in two or more family members according to present evidence
 in the literature. It is also known that AIP mutation is usually associated with more
 aggressive clinical behavior due to unclarified reasons.

 The prevalence of AIP mutation in Turkish population and types of mutations have not been
 defined previously. The primary aim of the present study is to define the AIP gene mutation
 prevalence and the relation with clinical and tumour behaviour in a subgroup of Turkish
 acromegalic patients. If AIP gene mutation is detected in some patients, it will be possible
 to screen the family of the patient for the presence of AIP mutation or at least for the
 presence of pituitary adenoma.

 Acromegalic patients who are followed in Erciyes University Medical School Department of
 Endocrinology will be enrolled into the study. After DNA isolation, each exon of AIP gene
 including splicing points will be reproduced by polymerase chain reaction (PCR) and will be
 analyzed for the presence of mutation by sequence analysis. The cases will be analyzed
 further in means of clinical features according to presence of AIP gene mutation.

 The prevalence of AIP gene mutation, clinical reflection of presence of AIP mutation will be
 determined and genetic consultation will be given to the carriers of AIP gene mutation at the
 end of the study.
Screening for AIP gene mutation is recommended in patients with pituitary adenomas of
 childhood-onset, GH or PRL secreting tumors who are diagnosed before the age of 30 years and
 positive family history in two or more family members according to present evidence in the
 literature. It is also known that AIP mutation is usually associated with more aggressive
 clinical behavior due to unclarified reasons.

 The prevalence of AIP mutation in Turkish population and types of mutations have not been
 defined previously. The primary aim of the present study is to define the AIP gene mutation
 prevalence and the relation with clinical and tumour behavior in a subgroup of Turkish
 acromegalic patients. If AIP gene mutation is detected in some patients, it will be possible
 to screen the family of the patient for the presence of AIP mutation or at least for the
 presence of pituitary adenoma.

 Acromegalic patients who are followed in Erciyes University Medical School Department of
 Endocrinology will be enrolled into the study. The clinical and laboratory data will be
 recorded and the remission status of the patients will be determined. Each exon of AIP gene
 including splicing points will be reproduced by PCR and will be analyzed for the presence of
 mutation by sequence analysis. Genomic DNA will be isolated from peripheral blood samples of
 acromegalic patients by using the QIAamp DNA blood mini kit (QIA-GEN, Milano, Italy)
 according to the manufacturer's instruction. Fifty nanograms of genomic DNA will be ampliﬁed
 with primers as reported. The entire AIP gene will be examined acromegaly patients and
 healthy control group. Each AIP exon from each DNA sample will be ampliﬁed using PCR. Six AIP
 exons will be ampliﬁed using the Thermo Taq DNA polymerase and following conditions: an
 initial denaturation at 96°C for 5 min, followed by 34 cycles of 94°C for 45 s, 60°C for 45
 s, 72°C for 1 min, then a ﬁnal extension step at 72°C for 7 min.PCR ampliﬁcations will be
 checked on a 2 % agarose gel. PCR products will be purified by PCR purification kit.
 Sequential alterations will be determined by bidirectional sequencing. Six AIP exons will be
 sequenced by using Beckman CEQ 8000.

 The cases will be analyzed further in means of clinical features according to presence of AIP
 gene mutation.

 The prevalence of AIP gene mutation, clinical reflection of presence of AIP mutation will be
 determined and genetic consultation will be given to the carriers of AIP gene mutation at the
 end of the study.
Inclusion Criteria:

 * Patients with acromegaly

 Exclusion Criteria:

 * Patients with acromegaly due to ectopic GH or GHRH secreting tumors