Odonto-hypophosphatasia with Tooth Agenesis: a Case Report

Area of Science:

• Genetics
• Dentistry
• Biochemistry

Background:

• Odonto-hypophosphatasia (odonto-HPP) is a mild hypophosphatasia (HPP) variant causing premature tooth loss and low serum alkaline phosphatase (ALP).
• Tooth agenesis (TA) is a common developmental anomaly involving the congenital absence of teeth.
• Simultaneous occurrence of odonto-HPP and TA is rare and not previously reported in families.

Purpose of the Study:

• To report the first family diagnosed with both odonto-HPP and TA.
• To investigate the genetic basis of this co-occurrence.
• To explore potential novel genetic links between HPP and dental anomalies.

Main Methods:

• Clinical evaluation of a family with dental abnormalities.
• Comprehensive genetic analysis including whole-exome sequencing.
• Identification and characterization of variants in the ALPL gene and known TA genes.

Main Results:

• Two novel missense variants (c.103G>A and c.247G>A) in the ALPL gene were identified in affected family members.
• These ALPL variants are associated with odonto-HPP.
• No pathogenic variants were found in established TA-associated genes, suggesting ALPL's role.

Conclusions:

• This study presents the first family with co-occurring odonto-HPP and TA.
• Novel ALPL gene variants expand the known genetic spectrum of odonto-HPP.
• HPP may be associated with additional, previously unrecognized dental abnormalities like TA.