ClinVar

In a female infant in whom the diagnosis of autosomal recessive polycystic kidney disease (PKD4; 263200) was made in utero, Ward et al. (2002) found a 107C-T transition in exon 3 of the PKHD1 gene resulting in a thr36-to-met (T36M) amino acid substitution in fibrocystin. The infant, who had congenital hepatic fibrosis, required mechanical ventilation at birth and was hypertensive. The patient suffered hematemesis at 3 years of age and had variceal banding.

Bergmann et al. (2003) concluded that the T36M mutation represents a mutation hotspot because it is recurrent and observed in a variety of populations.

Ward et al. (2011) estimated the frequency of T36M to be 3.2% in the European population. Ward et al. (2011) observed an association between the common T36M allele and protection against colorectal cancer (114500). Germline heterozygosity for the mutant allele was found in 0.42% of 3,603 healthy European controls and in 0.027% of 3,767 patients with colorectal cancer (p = 0.0002; odds ratio of 0.072). The authors postulated that reduced fibrocystin activity may enhance mitotic instability, which may inhibit carcinogenesis.