PCDH19-Related Epileptic Encephalopathy in a Male Mosaic for a Truncating Variant

被引：37

作者：

Thiffault, Isabelle ^{[1
,2
,3
]}

Farrow, Emily ^{[1
,3
]}

Smith, Laurie ^{[1
,4
]}

Lowry, Jennifer ^{[3
,5
,6
]}

Zellmer, Lee ^{[1
]}

Black, Benjamin ^{[5
]}

Abdelmoity, Ahmed ^{[6
]}

Miller, Neil ^{[1
]}

Soden, Sarah ^{[1
,3
,5
,6
]}

Saunders, Carol ^{[1
,2
,3
]}

机构：

[1] Childrens Mercy Hosp, Ctr Pediat Genom Med, Kansas City, MO 64108 USA

[2] Childrens Mercy Hosp, Dept Pathol & Lab Med, Kansas City, MO 64108 USA

[3] Univ Missouri, Sch Med, Kansas City, MO 64108 USA

[4] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA

[5] Childrens Mercy Hosp, Individualized Pediat Therapeut Med Clin, Kansas City, MO 64108 USA

[6] Childrens Mercy Hosp, Dept Pediat, Kansas City, MO 64108 USA

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART A | 2016年 / 170卷 / 06期

关键词：

PCDH19; epileptic encephalopathy; developmental disorders; behavioral disorders; somatic mosaicism; dysmorphic features; OF-FUNCTION MUTATIONS; PCDH19; MUTATIONS; DE-NOVO; MENTAL-RETARDATION; PHENOTYPIC SPECTRUM; DRAVET SYNDROME; FEMALES; DISORDER; SCN1A;

D O I：

10.1002/ajmg.a.37617

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Variants in the X-linked gene PCDH19 are associated with early infantile epileptic encephalopathy-9. This unusual condition spares hemizygous males except for psychiatric and behavioral abnormalities, and for this reason is also known as female limited epilepsy. Some cases are due to de novo PCDH19 variants, but may also be paternally inherited. Our patient is a 6-year-old male with epileptic encephalopathy. Exome sequencing revealed apparent heterozygosity in PCDH19 for a novel nonsense variant, c.605C>A (p.Ser202*), inconsistent with expectations for a male. Testing of other tissues revealed a mixture of mutant and normal alleles. These results are consistent with somatic mosaicism for p.Ser202*. This is the second male with somatic mosaicism for PCDH19 deficiency, providing further support for cellular interference as the pathogenic mechanism for this condition, which leads to this unusual mode of inheritance in which females are more severely affected than males. (C) 2016 Wiley Periodicals, Inc.

引用

页码：1585 / 1589

页数：5

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