Novel PIBF1 Pathogenic Variant in Three Siblings with Joubert Syndrome Type 33

Area of Science:

• Genetics
• Rare Diseases
• Neurology

Background:

• Joubert syndrome type 33 (JBTS33) is a rare autosomal recessive disorder.
• Characterized by developmental delay, severe renal disease, hypotonia/ataxia, cerebellar abnormalities, and optic nerve atrophy.
• Over 40 genes are associated with JBTS, including CEP290, TMEM216, TMEM67, AHI1, and CC2D2A.

Purpose of the Study:

• To identify the genetic cause of JBTS33 in a consanguineous family.
• To expand the known molecular and clinical spectrum of JBTS.

Main Methods:

• Whole-exome sequencing was performed on a consanguineous family.
• A novel biallelic homozygous nonsense mutation in the progesterone-induced blocking factor 1 (PIBF1) gene was identified.

Main Results:

• Three patients with the same homozygous PIBF1 mutation exhibited psychomotor issues, dysmorphic features, hypotonia/ataxia, and kidney failure.
• Seizures in all three patients were resolved with phenobarbital.
• The identified PIBF1 mutation is novel and not present in public databases.

Conclusions:

• PIBF1 is confirmed as a disease-causing gene for JBTS33.
• This finding broadens the understanding of PIBF1 mutations and their associated clinical manifestations.
• Increased diagnostic awareness of PIBF1 mutations can improve early intervention and patient management.