PRRT2-related phenotypes in patients with a 16p11.2 deletion.
Eur J Med Genet
; 62(4): 265-269, 2019 Apr.
Article
em En
| MEDLINE
| ID: mdl-30125676
ABSTRACT
We studied the presence of benign infantile epilepsy (BIE), paroxysmal kinesigenic dyskinesia (PKD), and PKD with infantile convulsions (PKD/IC) in patients with a 16p11.2 deletion including PRRT2 or with a PRRT2 loss-of-function sequence variant. Index patients were recruited from seven Dutch university hospitals. The presence of BIE, PKD and PKD/IC was retrospectively evaluated using questionnaires and medical records. We included 33 patients with a 16p11.2 deletion three (9%) had BIE, none had PKD or PKD/IC. Twelve patients had a PRRT2 sequence variant BIE was present in four (pâ¯=â¯0.069), PKD in six (pâ¯<â¯0.001) and PKD/IC in two (pâ¯=â¯0.067). Most patients with a deletion had undergone genetic testing because of developmental problems (87%), whereas all patients with a sequence variant were tested because of a movement disorder (55%) or epilepsy (45%). BIE, PKD and PKD/IC clearly showed incomplete penetrance in patients with 16p11.2 deletions, but were found in all and 95% of patients with a PRRT2 sequence variant in our study and a large literature cohort, respectively. Deletions and sequence variants have the same underlying loss-of-function disease mechanism. Thus, differences in ascertainment have led to overestimating the frequency of BIE, PKD and PKD/IC in patients with a PRRT2 sequence variant. This has important implications for counseling if genome-wide sequencing shows such variants in patients not presenting the PRRT2-related phenotypes.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
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Transtorno Autístico
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Transtornos Cromossômicos
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Proteínas de Membrana
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Deficiência Intelectual
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Proteínas do Tecido Nervoso
Limite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Eur J Med Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Holanda