pre-MIR7-2 CHNG3

Nongoitrous congenital hypothyroidism-3 (CHNG3) is characterized by infantile-onset clinical and subclinical hypothyroidism associated with a small thyroid gland, high circulating TSH, normal free T4 levels, and normal or mildly increased serum thyroglobulin. Untreated patients or patients who discontinue treatment show a characteristic transition to multinodular goiter (MNG) with age¹.

Prevalence

Found in 12 families, with ancestry including: Irish, White European, French (Normandie), Ashkenazi, French Canadian, Danish/White European, Welsh, Scottish, Italian, British/White European, Italian/Turkish/Lebanese, German/Palestinian, and South Chinese².

Age of Onset Details

0 (birth)

Locus

hg19

chr15:89112665-89112680

hg38

chr15:88569434-88569449

t2t

chr15:86324039-86324054

Details

Deletion of one repeat (4 to 3 repeats) found in 10 unrelated families with unsolved disease³; a heterozygous T-to-G transversion in the third repeat can also lead to disease².

Mechanism

GoF

Activates a thyroid-specific enhancer^2,3.

Year

2024³

Gene Strand

Alleles

Ref. Motif

AAAC

Pathogenic (ref.)

AAAC

Pathogenic (gene)

GTTT

References

Direct supporting references for info on this page.

omim:609893

Functional variants in a TTTG microsatellite on 15q26.1 cause familial nonautoimmune thyroid abnormalities.

Satoshi,Narumi, Keisuke,Nagasaki, Mitsuo,Kiriya, Erika,Uehara, Kazuhisa,Akiba, Kanako,Tanase-Nakao, Kazuhiro,Shimura, Kiyomi,Abe, Chiho,Sugisawa, Tomohiro,Ishii, Kenichi,Miyako, Yukihiro,Hasegawa, Yoshihiro,Maruo, Koji,Muroya, Natsuko,Watanabe, Eijun,Nishihara, Yuka,Ito, Takahiko,Kogai, Kaori,Kameyama, Kazuhiko,Nakabayashi, Kenichiro,Hata, Maki,Fukami, Hirohito,Shima, Atsuo,Kikuchi, Jun,Takayama, Gen,Tamiya, Tomonobu,Hasegawa

Nature genetics · 2024-05-07

pmid:38714868

STR mutations on chromosome 15q cause thyrotropin resistance by activating a primate-specific enhancer of MIR7-2/MIR1179.

Helmut,Grasberger, Alexandra M,Dumitrescu, Xiao-Hui,Liao, Elliott G,Swanson, Roy E,Weiss, Panudda,Srichomkwun, Theodora,Pappa, Junfeng,Chen, Takashi,Yoshimura, Phillip,Hoffmann, Monica Malheiros,França, Rebecca,Tagett, Kazumichi,Onigata, Sabine,Costagliola, Jane,Ranchalis, Mitchell R,Vollger, Andrew B,Stergachis, Jessica X,Chong, Michael J,Bamshad, Guillaume,Smits, Gilbert,Vassart, Samuel,Refetoff

Nature genetics · 2024-05-07

pmid:38714869