Amelogenesis imperfecta
Gene: KLK4Comment 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.
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/KLK4Created: 3 Aug 2017, 1:19 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Amelogenesis imperfecta, type IIA1 204700
Publications
This panel has been promoted after review by Claire Smith (Leeds) and further personal consultation with Dr Smith
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Mode of inheritance for KLK4 was changed to BIALLELIC, autosomal or pseudoautosomal
Publications for KLK4 were set to 15235027; 23355523; 26124219; 28611678
Phenotypes for KLK4 were set to Amelogenesis imperfecta, type IIA1, 204700; Amelogenesis Imperfecta, Hypomaturation Type, IIA1, 204700
KLK4 was added to Amelogenesis Imperfectapanel. Source: UKGTN Model of inheritance for gene KLK4 was set to BIALLELIC, autosomal or pseudoautosomal
KLK4 was added to Amelogenesis Imperfectapanel. Source: Radboud University Medical Center, Nijmegen
KLK4 was added to Amelogenesis Imperfectapanel. Sources: Eligibility statement prior genetic testing
KLK4 was created by rfoulger