aHUS genetic counselling-evidence based

Some new aHUS Research* was presented at the recent meeting of the International Pediatric Nephrology Association in Venice. A talk by Dr Gianluigi Ardissino addressed the issue of genetic testing of aHUS families where some healthy members may yet be affected by the disease.

When an aHUS Patient is referred to Dr Ardissino’s clinic in Milan ( Fondazione IRCCS CA’Grande Ospedale Maggiore Policlinico Milano) and is found to have a mutation in their Complement regulatory genes, then other members of their family are offered genetic testing if they are interested.

The clinic has genetic data on 279 people, 107 patients and 172 healthy carriers, from 75 families. Their mean age is 35 +/- 21 years.

In 61 families only one person had onset with aHUS, a sporadic case as it is known ( but maybe familial in time). In 14 families there was more than one family member who had on set with aHUS.

There were 29 aHUS patients in those  14 families. and 13 of them were siblings of the premier  patient referred , 11 were offspring and 3 were parents.

In the Italian families a far lower penetrance of the disease than expected was found. Disease development in other family members was low, although the risk was unequally distributed over the generations. Siblings and offspring being at greater risk than the parents of the first  patient.

The Ardissino group concluded that  results such as these would be important information for genetic counselling.

The Group also thought their findings supported the concept that a second genetic hit from the non affected/ non carrying parent may influence penetrance in subsequent generations and that is worthy of further exon sequencing investigation.

* Disease risk among family members of patients  with aHUS carrying Complement regulatory gene abnormality. IPN 10798-96.

G. Ardissino  B. Strumbo V. Capone D. Cresseri S. Longhi L. Martelli G. Loffredo  L. Porcaro P. Messa G. Montini S. Tedeschi