Aggressive pituitary adenomas occurring in young patients in a large Polynesian kindred with a germline R271W mutation in the AIP gene.
OBJECTIVE
Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) were recently shown to confer a pituitary adenoma predisposition in patients with familial isolated pituitary adenomas (FIPA). We report a large Samoan FIPA kindred from Australia/New Zealand with an R271W mutation that was associated with aggressive pituitary tumors.


METHODS
Case series with germline screening of AIP and haplotype analyses among R271W families.


RESULTS
This previously unreported kindred consisted of three affected individuals that either presented with or had first symptoms of a pituitary macroadenoma in late childhood or adolescence. The index case, a 15-year-old male with incipient gigantism and his maternal aunt, had somatotropinomas, and the maternal uncle of the index case had a prolactinoma. All tumors were large (15, 40, and 60 mm maximum diameter) and two required transcranial surgery and radiotherapy. All three affected subjects and ten other unaffected relatives were found to be positive for a germline R271W AIP mutation. Comparison of the single nucleotide polymorphism patterns among this family and two previously reported European FIPA families with the same R271W mutation demonstrated no common ancestry.


CONCLUSIONS
This kindred exemplifies the aggressive features of pituitary adenomas associated with AIP mutations, while genetic analyses among three R271W FIPA families indicate that R271W represents a mutational hotspot that should be studied further in functional studies.
Jennings
Juliet E
JE
Department of Endocrinology and Diabetes and Centre for Hormone Research, The Murdoch Childrens Research Institute and The Royal Children's Hospital, Flemington Road, Parkville, Melbourne, Victoria 3052, Australia.
Georgitsi
Marianthi
M
Holdaway
Ian
I
Daly
Adrian F
AF
Tichomirowa
Maria
M
Beckers
Albert
A
Aaltonen
Lauri A
LA
Karhu
Auli
A
Cameron
Fergus J
FJ
D000236:Adenoma / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001315:Australia; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D018095:Germ-Line Mutation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D009520:New Zealand; D010375:Pedigree; D010911:Pituitary Neoplasms / Q000235:genetics*; D017354:Point Mutation; D011114:Polynesia / Q000208:ethnology; D017422:Sequence Analysis, DNA; D055815:Young Adult
D047908:Intracellular Signaling Peptides and Proteins; C103265:aryl hydrocarbon receptor-interacting protein; D004247:DNA