Diagnostic Approach of Van Buggenhout and Fryns for Identifying the Genetic Defect Causing Angelman's Syndrome in a Patient

Van Buggenhout and Fryns reported an approach for identifying the genetic defect causing Angelman's Syndrome (AS) in a patient.

Initial assessment:

(1) cytogenetics with evaluation of chromosome 15

(2) DNA methylation test

Defect on Chromosome 15	DNA Methylation Test	Diagnosis
Visible	NA	large deletion, translocation or inversion
none visible	normal	defect UBE3A
none visible	abnormal	deletion 15q11.2-q13
none visible	abnormal	paternal uniparental disomy (UPD)
none visible	abnormal	IC defect with deletion
none visible	abnormal	IC defect without deletion
none visible	other	unidentified

Diagnosis	Percent of Cases	Recurrence Risk
large deletion, translocation or inversion	< 1%	NA
defect UBE3A	10%	50% if gene mutation from mother; 1% if de novo
deletion 15q11.2-q13	60 to 75%	50% if gene mutation from mother; 1% if de novo
paternal uniparental disomy (UPD)	2 to 5%	100% if Robertsonian translocation; < 1% if sporadic
imprinting center (IC) defect with deletion	*	50% with gene mutation from mother
IC defect without deletion	*	< 1%
unidentified	5 to 26%	NA

where:

• The frequency of all IC defects (*) is 2 to 5%.

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