Amelogenesis imperfecta

Gene: KLK4

Comment when marking as ready: Marked as ready: August 16th 2017.

Created: 16 Aug 2017, 9:33 a.m.

Comment on list classification: Updated rating from Amber to Green: Green expert review plus on Leeds diagnostic panel. 2 variants (2 African American siblings and an unrelated Turkish girl) reported in OMIM (W153X and 1bp deletion c.245delG). 2 further variants curated in LOVD and reported by Claire Smith (frameshift at p.Ser207 and the 4th KLK4 variant (c.632delT) which may be a common cause of AI in the Pakistani population (PMID:28611678).

Created: 16 Aug 2017, 9:32 a.m.

Comment on mode of inheritance: Biallelic MOI also supported by OMIM.

Created: 16 Aug 2017, 9:23 a.m.

Green List (high evidence)

Currently on the Leeds AI diagnostic panel (Contact: Ruth Charlton). Associated with hypomaturation AI. KLK4 mutations cause autosomal recessive hypomaturation AI (Hart et al., 2004). All four KLK4 variants reported so far are either nonsense or frameshift mutations. However, only two of the four are predicted to lead to NMD. Of the two frameshift mutations affecting codons in the final exon, and therefore not expected to undergo NMD, one alters one of the three catalytic residues, p.S207, essential to the function of all kallikrein enzymes. The c.632delT variant, reported to occur at a frequency of 0.15% in the South Asian population, has been reported in five Pakistani families with hypomaturation AI. See KLK4 LOVD: http://dna2.leeds.ac.uk/LOVD/genes/KLK4

Created: 3 Aug 2017, 1:19 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Amelogenesis imperfecta, type IIA1 204700

Publications

• PMID: 15235027
• 23355523
• 26124219
• 28611678