Fourteen Monogenic Genes Account for 15% of Nephrolithiasis/Nephrocalcinosis

被引：175

作者：

Halbritter, Jan ^{[1
]}

Baum, Michelle ^{[1
]}

Hynes, Ann Marie ^{[4
]}

Rice, Sarah J. ^{[4
,5
]}

Thwaites, David T. ^{[5
]}

Gucev, Zoran S. ^{[6
]}

Fisher, Brittany ^{[1
]}

Spaneas, Leslie ^{[1
]}

Porath, Jonathan D. ^{[1
]}

Braun, Daniela A. ^{[1
]}

Wassner, Ari J. ^{[2
]}

Nelson, Caleb P. ^{[3
]}

Tasic, Velibor ^{[6
]}

Sayer, John A. ^{[4
]}

Hildebrandt, Friedhelm ^{[1
,7
]}

机构：

[1] Harvard Univ, Sch Med, Div Nephrol, Dept Med, Boston, MA USA

[2] Harvard Univ, Sch Med, Div Endocrinol, Dept Med, Boston, MA USA

[3] Harvard Univ, Sch Med, Dept Urol, Boston Childrens Hosp, Boston, MA USA

[4] Newcastle Univ, Inst Med Genet, Int Ctr Life, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England

[5] Newcastle Univ, Epithelial Res Grp, Inst Cell & Mol Biosci, Fac Med Sci, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England

[6] Univ Childrens Hosp, Med Fac Skopje, Skopje, Macedonia

[7] Howard Hughes Med Inst, Chevy Chase, MD USA

来源：

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2015年 / 26卷 / 03期

基金：

美国国家卫生研究院;

关键词：

KIDNEY-STONES; MUTATIONS; CYSTINURIA; SLC7A9; NEPHROLITHIASIS; HYPERCALCIURIA; IDENTIFICATION; DIAGNOSIS; SLC3A1;

D O I：

10.1681/ASN.2014040388

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Nephrolithiasis is a prevalent condition with a high morbidity. Although dozens of monogenic causes have been identified, the fraction of single-gene disease has not been well studied. To determine the percentage of cases that can be molecularly explained by mutations in 1 of 30 known kidney stone genes, we conducted a high-throughput mutation analysis in a cohort of consecutively recruited patients from typical kidney stone clinics. The cohort comprised 272 genetically unresolved individuals (106 children and 166 adults) from 268 families with nephrolithiasis (n=256) or isolated nephrocalcinosis (n=16). We detected 50 likely causative mutations in 14 of 30 analyzed genes, leading to a molecular diagnosis in 14.9% (40 of 268) of all cases; 20 of 50 detected mutations were novel (40%). The cystinuria gene SLC7A9 (n=19) was most frequently mutated. The percentage of monogenic cases was notably high in both the adult (11.4%) and pediatric cohorts (20.8%). Recessive causes were more frequent among children, whereas dominant disease occurred more abundantly in adults. Our study provides an in-depth analysis of monogenic causes of kidney stone disease. We suggest that knowledge of the molecular cause of nephrolithiasis and nephrocalcinosis may have practical implications and might facilitate personalized treatment.

引用

页码：543 / 551

页数：9

共 31 条

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