Recessive Mutations in KIF12 Cause High Gamma-Glutamyltransferase Cholestasis

被引：28

作者：

Aksu, Aysel Unlusoy ^{[1
]}

Das, Subhash K. ^{[2
]}

Nelson-Williams, Carol ^{[3
]}

Jain, Dhanpat ^{[2
,4
]}

Hosnut, Ferda Ozbay ^{[1
]}

Sahin, Gulseren Evirgen ^{[1
]}

Lifton, Richard P. ^{[3
,5
,6
]}

Vilarinho, Silvia ^{[2
,4
]}

机构：

[1] Univ Hlth Sci, Dr Sami Ulus Matern & Child Hlth & Dis Training &, Dept Pediat Gastroenterol Hepatol & Nutr, Ankara, Turkey

[2] Yale Univ, Dept Internal Med, Sect Digest Dis, Sch Med, New Haven, CT 06510 USA

[3] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA

[4] Yale Univ, Sch Med, Dept Pathol, 333 Cedar St,LMP1080, New Haven, CT 06510 USA

[5] Yale Univ, Sch Med, Yale Ctr Mendelian Genom, New Haven, CT 06510 USA

[6] Rockefeller Univ, Lab Human Genet & Genom, 1230 York Ave, New York, NY 10021 USA

来源：

HEPATOLOGY COMMUNICATIONS | 2019年 / 3卷 / 04期

基金：

美国国家卫生研究院;

关键词：

KINESIN; MODIFIER; PROTEIN;

D O I：

10.1002/hep4.1320

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Undiagnosed liver disease remains an unmet medical need in pediatric hepatology, including children with high gamma-glutamyltransferase (GGT) cholestasis. Here, we report whole-exome sequencing of germline DNA from 2 unrelated children, both offspring of consanguineous union, with neonatal cholestasis and high GGT of unclear etiology. Both children had a rare homozygous damaging mutation (p.Arg219* and p.Val204Met) in kinesin family member 12 (KIF12). Furthermore, an older sibling of the child homozygous for p.Va1204Met missense mutation, who was also found to have cholestasis, had the same homozygous mutation, thus identifying the cause of the underlying liver disease. Conclusion: Our findings implicate rare homozygous mutations in KIF12 in the pathogenesis of cholestatic liver disease with high GGT in 3 previously undiagnosed children.

引用

页码：471 / 477

页数：7

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