Evidence map›Paper›PMID 39315525›Full record

ArticleGenetics in medicine : official journal of the American College of Medical Genetics2025

The role of double heterozygotes of SLC3A1 and SLC7A9 in the prevalence of cystine stones.

Chen-Han Wilfred Wu, Ishita Patel, Katreya Lovrenert, Brian Eisner, Naomi Meeks, Anne Chun-Hui Tsai, Michelle Baum, Gerard Berry, Fredrick R Schumacher

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Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Chen-Han Wilfred WuDepartment of Urology and Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine and University Hospitals, Cleveland, OH. Electronic address: wilfred.wu@case.edu.
Ishita PatelDepartment of Urology and Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine and University Hospitals, Cleveland, OH.
Katreya LovrenertDepartment of Urology and Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine and University Hospitals, Cleveland, OH.
Brian EisnerMassachusetts General Hospital/Harvard Medical School, Boston, MA.
Naomi MeeksDivision of Clinical Genetics and Metabolism, Department of Pediatrics, Children's Hospital Colorado and University of Colorado, Aurora, CO.
Anne Chun-Hui TsaiSection of Genetics, Department of Pediatrics, University of Illinois Chicago, Chicago, IL.
Michelle BaumDivision of Nephrology, Boston Children's Hospital/Harvard Medical School, Boston, MA.
Gerard BerryDivision of Genetics and Genomics, Boston Children's Hospital/Harvard Medical School, Boston, MA.
Fredrick R SchumacherDepartment of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH.

Funding

TRAINING GRANT IN GENETICST32GM007748 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Anne O'Donnell-Luria, Louise Wilkins-Haug · 1985 to 2026
$12.0M
A comprehensive approach to understanding the genetic causes of urinary stone disease: combining monogenic and polygenic analysesK08DK135933 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Chen-Han Wilfred Wu · 2024 to 2026
$486k
NIDDK NIH HHS K08 DK135933NIGMS NIH HHS T32 GM007748
6 · The paper itself

Abstract

purposeCystine stones, an autosomal recessive disorder caused by cystinuria, result from pathogenic variants of SLC3A1 and SLC7A9. Previous publications revealed that clinical prevalence is higher than genetically predicted prevalence. Heterozygotes in either gene are not stone formers. However, double heterozygotes (DH), individuals with 2 heterozygous pathogenic variants in both genes, were never evaluated and may explain the gap between clinical and genetic prevalence.

methodsBecause of the rarity of the condition, direct clinical observation is impractical. We perform this population study as a surrogate by identifying the observed DH, deriving the theoretical/expected DH, and testing the null hypothesis (NH) that the observed DH frequency is equal or greater than expected. This NH biologically correlate to that DH are asymptomatic and do not have cystine stone.

resultsUsing the 1000 Genome Database, we identified 0 DH. We derived the theoretical/expected DH with Hardy-Weinberg Equilibrium and Mendel's law of independent assortment as 4.94 × 10-s. Population proportion test revealed z = -0.353, and P = .362, the NH cannot be rejected.

conclusionStatistical testing does not support that DH are symptomatic, ie, DH of SLC3A1 and SLC7A9 may not present with cystine stone, and other factors responsible for the gap that current genetics knowledge cannot explain.

Indexed as

CystinuriaHeterozygoteAmino Acid Transport Systems, BasicAmino Acid Transport Systems, NeutralAmino Acid Transport System y+CystineHumansPrevalenceAmino Acid Transport Systems, BasicAmino Acid Transport Systems, NeutralAmino Acid Transport System y+CystineSLC3A1 protein, humanSLC7A9 protein, humanCystine stoneCystinuriaDouble heterozygoteHeterozygosityPopulation genetics

Identifiers

PMID39315525
PMCPMC11717588

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.