Pituitary hormone deficiency

Gene: TTC26

Green List (high evidence)

Comment on list classification: There are more than 3 unrelated individuals reported in literature with biallelic TTC26 variants and a multisystem ciliopathy with pituitary involvement. Patients exhibited impaired pituitary function. Pituitary anomalies e.g., pituitary hypoplasia / stalk interruption, were seen on MRI in 5 different families. Animal models support function of TTC26 in ciliogenesis and ciliary function. Hence, this gene should be promoted to Green at the next update.

Created: 22 Apr 2026, 1:08 p.m. | Last Modified: 22 Apr 2026, 1:08 p.m.

Panel Version: 4.6

PMID: 31595528 Shaheen et al., 2020
Report of seven individuals from seven families with syndromic ciliopathy clinical features, including severe neonatal cholestasis (lethal in one, required liver transplant in two cases). Other features: polydactyly (5/7), echogenic kidneys with impaired renal function (5/7), variable cardiac anomalies (5/7).
TTC26 variants detected: NM_024926.4: c.788A>G, p.Asn263Ser (4 patients, shared haplotype); c.1331C>T, p.Pro444Leu (1 patient, and c.4-1G>C (2 patients).

PMID: 32617964 David et al., 2020
Four patients from two apparently unrelated consanguineous Bedouin families with ciliopathy due to a homozygous TTC26 c.695A>G p.Asn232Ser mutation. Patients had dysmorphic features, early-onset cholestatic jaundice (4/4), pituitary hormone deficiency (2/4), postaxial polydactyly (3/4), ectopic / absent neurohypophysis (posterior lobe of the pituitary gland) on brain MRI (3/4).

PMID: 34177428 Alfadhel et al., 2021
Nonconsanguineous Saudi family. The female proband exhibited cholestasis, cystic dilatation of intrahepatic biliary ducts, diabetes insipidus, dysmorphic facial features, optic atrophy, hydrocephalus, aqueductal stenosis, hyperextensible knee joints, bilateral knee dislocation, polydactyly, and syndactyly. Brain MRI showed pituitary hypoplasia. She died at 15 months of age.
WGS + Sanger sequencing revealed a homozygous TTC26 variant (c.4-1G>C; NM_024926.3).

PMID: 38135897 Papingi et al., 2024
Male patient with hexadactyly, pituitary stalk interruption, hepatopathy, nephropathy, unilateral hearing impairment, a congenital heart defect, and a bilateral lip-palate cleft. He was homozygous for TTC26 c.1006-5T> C. Parents are first degree-cousins, Afghan ancestry.

PMID: 39514123 Yang et al., 2025
Chinese case of BRENS syndrome who exhibited bilateral small kidney size and abnormal kidney function, cryptorchidism and short penis, optic atrophy, pituitary anomalies (including missing pituitary stalk on imaging), hexadactyly, congenital cardiac defect, thyroid dysfunction, partial hypopituitarism, and other features (though no biliary involvement). 3 TTC26 variant detected: c.1069+5G>A inherited from the mother and c.511A>G (p.Ile171Val) and c.1099T>C (p.Ser367Pro) from the father.

Functional evidence:
PMID: 24596149 Ishikawa et al., 2014 - Knockdown of ttc26 in zebrafish embryos or mutation of Dyf13 (TTC26 ortholog) in C. reinhardtii produced short cilia with abnormal motility.

TTC26 is associated with AR Biliary, renal, neurologic, and skeletal syndrome, OMIM:619534 (OMIM accessed 22nd Apr 2026).
Sources: Literature

Created: 22 Apr 2026, 12:46 p.m. | Last Modified: 22 Apr 2026, 1:06 p.m.

Panel Version: 4.5

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Biliary, renal, neurologic, and skeletal syndrome, OMIM:619534; biliary, renal, neurologic, and skeletal syndrome, MONDO:0859191

Publications

• 31595528
• 32617964
• 34177428
• 38135897
• 39514123