Genotype-phenotype correlation in biallelic TNSALP mutations

• Research type

  Research Study

• Full title

  The effect of biallelic TNSALP mutations on alkaline phosphatase structure, function and clinical phenotype in children with Hypophosphatasia

• IRAS ID

  237142

• Contact name

  Wolfgang Hoegler

• Contact email

  wolfgang.hogler@nhs.net

• Sponsor organisation

  Birmingham Women's and Children's Hospitals NHS Trust

• Duration of Study in the UK

  1 years, 5 months, 26 days

• Research summary

  Background:
  Hypophosphatasia (HPP) is a medical condition where an enzyme called the alkaline phosphatase (ALP) is lacking. ALP is important for bone formation as it facilitates deposition of minerals (such as calcium and phosphorus) into bones and teeth, necessary for bone and tooth stiffness and strength. In HPP the absence of ALP enzyme leads to soft bones and teeth which lack rigidity. The severity of the disease can vary from very severe life threatening disease at birth to isolated early tooth loss in adulthood. Generally, severely affected individuals have been found to have two affected gene copies inherited from both parents. However, mild to moderately affected individuals may have an affected gene copy inherited from one or both parents. In our clinical experience we have seen children who have been variably affected (clinically well or asymptomatic to life threatening) after inheriting two affected gene copies (biallelic mutations).
  Aims:
  1. 1. We wish to study the function of the ALP enzyme in children with HPP who have inherited 2 gene copies
  2. We wish to correlate the clinical and laboratory test findings to better understand the condition

  Methods:
  Review of clinical and laboratory data collected as part of routine clinical care in 6 pre-determined individuals with HPP due to biallelic mutation. ALP function using the affected gene code will be studied in a specialized laboratory in Tokyo, Japan. The individual's genetic code determined as part of routine care will be shared with the testing laboratory after parental consent.
  Expected outcome:
  Better understanding of the genotype- phenotype correlation in biallelic mutations in order to predict clinical severity of disease and outcome.

• REC name

  North West - Greater Manchester South Research Ethics Committee

• REC reference

  18/NW/0295

• Date of REC Opinion

  10 May 2018

• REC opinion

  Favourable Opinion