Congenital disorders

Novel missense variants cause intermediate phenotypes in the phenotypic spectrum of SLC5A6-related disorders

Posted on by yun

Abstract

SLC5A6 encodes the sodium-dependent multivitamin transporter, a transmembrane protein that uptakes biotin, pantothenic acid, and lipoic acid. Biallelic SLC5A6 variants cause sodium-dependent multivitamin transporter deficiency (SMVTD) and childhood-onset biotin-responsive peripheral motor neuropathy (COMNB), which both respond well to replacement therapy with the above three nutrients. SMVTD usually presents with various symptoms in multiple organs, such as gastrointestinal hemorrhage, brain atrophy, and global developmental delay, at birth or in infancy. Without nutrient replacement therapy, SMVTD can be lethal in early childhood. COMNB is clinically milder and has a later onset than SMVTD, at approximately 10 years of age. COMNB symptoms are mostly limited to peripheral motor neuropathy. Here we report three patients from one Japanese family harboring novel compound heterozygous missense variants in SLC5A6, namely NM_021095.4:c.[221C>T];[642G>C] p.[(Ser74Phe)];[(Gln214His)]. Both variants were predicted to be deleterious through multiple lines of evidence, including amino acid conservation, in silico predictions of pathogenicity, and protein structure considerations. Drosophila analysis also showed c.221C>T to be pathogenic. All three patients had congenital brain cysts on neonatal cranial imaging, but no other morphological abnormalities. They also had a mild motor developmental delay that almost completely resolved despite no treatment. In terms of severity, their phenotypes were intermediate between SMVTD and COMNB. From these findings we propose a new SLC5A6-related disorder, spontaneously remitting developmental delay with brain cysts (SRDDBC) whose phenotypic severity is between that of SMVTD and COMNB. Further clinical and genetic evidence is needed to support our suggestion.

This is a preview of subscription content, access via your institution

Access options

/* style specs start */
style{display:none!important}.LiveAreaSection-193358632 *{align-content:stretch;align-items:stretch;align-self:auto;animation-delay:0s;animation-direction:normal;animation-duration:0s;animation-fill-mode:none;animation-iteration-count:1;animation-name:none;animation-play-state:running;animation-timing-function:ease;azimuth:center;backface-visibility:visible;background-attachment:scroll;background-blend-mode:normal;background-clip:borderBox;background-color:transparent;background-image:none;background-origin:paddingBox;background-position:0 0;background-repeat:repeat;background-size:auto auto;block-size:auto;border-block-end-color:currentcolor;border-block-end-style:none;border-block-end-width:medium;border-block-start-color:currentcolor;border-block-start-style:none;border-block-start-width:medium;border-bottom-color:currentcolor;border-bottom-left-radius:0;border-bottom-right-radius:0;border-bottom-style:none;border-bottom-width:medium;border-collapse:separate;border-image-outset:0s;border-image-repeat:stretch;border-image-slice:100%;border-image-source:none;border-image-width:1;border-inline-end-color:currentcolor;border-inline-end-style:none;border-inline-end-width:medium;border-inline-start-color:currentcolor;border-inline-start-style:none;border-inline-start-width:medium;border-left-color:currentcolor;border-left-style:none;border-left-width:medium;border-right-color:currentcolor;border-right-style:none;border-right-width:medium;border-spacing:0;border-top-color:currentcolor;border-top-left-radius:0;border-top-right-radius:0;border-top-style:none;border-top-width:medium;bottom:auto;box-decoration-break:slice;box-shadow:none;box-sizing:border-box;break-after:auto;break-before:auto;break-inside:auto;caption-side:top;caret-color:auto;clear:none;clip:auto;clip-path:none;color:initial;column-count:auto;column-fill:balance;column-gap:normal;column-rule-color:currentcolor;column-rule-style:none;column-rule-width:medium;column-span:none;column-width:auto;content:normal;counter-increment:none;counter-reset:none;cursor:auto;display:inline;empty-cells:show;filter:none;flex-basis:auto;flex-direction:row;flex-grow:0;flex-shrink:1;flex-wrap:nowrap;float:none;font-family:initial;font-feature-settings:normal;font-kerning:auto;font-language-override:normal;font-size:medium;font-size-adjust:none;font-stretch:normal;font-style:normal;font-synthesis:weight style;font-variant:normal;font-variant-alternates:normal;font-variant-caps:normal;font-variant-east-asian:normal;font-variant-ligatures:normal;font-variant-numeric:normal;font-variant-position:normal;font-weight:400;grid-auto-columns:auto;grid-auto-flow:row;grid-auto-rows:auto;grid-column-end:auto;grid-column-gap:0;grid-column-start:auto;grid-row-end:auto;grid-row-gap:0;grid-row-start:auto;grid-template-areas:none;grid-template-columns:none;grid-template-rows:none;height:auto;hyphens:manual;image-orientation:0deg;image-rendering:auto;image-resolution:1dppx;ime-mode:auto;inline-size:auto;isolation:auto;justify-content:flexStart;left:auto;letter-spacing:normal;line-break:auto;line-height:normal;list-style-image:none;list-style-position:outside;list-style-type:disc;margin-block-end:0;margin-block-start:0;margin-bottom:0;margin-inline-end:0;margin-inline-start:0;margin-left:0;margin-right:0;margin-top:0;mask-clip:borderBox;mask-composite:add;mask-image:none;mask-mode:matchSource;mask-origin:borderBox;mask-position:0 0;mask-repeat:repeat;mask-size:auto;mask-type:luminance;max-height:none;max-width:none;min-block-size:0;min-height:0;min-inline-size:0;min-width:0;mix-blend-mode:normal;object-fit:fill;object-position:50% 50%;offset-block-end:auto;offset-block-start:auto;offset-inline-end:auto;offset-inline-start:auto;opacity:1;order:0;orphans:2;outline-color:initial;outline-offset:0;outline-style:none;outline-width:medium;overflow:visible;overflow-wrap:normal;overflow-x:visible;overflow-y:visible;padding-block-end:0;padding-block-start:0;padding-bottom:0;padding-inline-end:0;padding-inline-start:0;padding-left:0;padding-right:0;padding-top:0;page-break-after:auto;page-break-before:auto;page-break-inside:auto;perspective:none;perspective-origin:50% 50%;pointer-events:auto;position:static;quotes:initial;resize:none;right:auto;ruby-align:spaceAround;ruby-merge:separate;ruby-position:over;scroll-behavior:auto;scroll-snap-coordinate:none;scroll-snap-destination:0 0;scroll-snap-points-x:none;scroll-snap-points-y:none;scroll-snap-type:none;shape-image-threshold:0;shape-margin:0;shape-outside:none;tab-size:8;table-layout:auto;text-align:initial;text-align-last:auto;text-combine-upright:none;text-decoration-color:currentcolor;text-decoration-line:none;text-decoration-style:solid;text-emphasis-color:currentcolor;text-emphasis-position:over right;text-emphasis-style:none;text-indent:0;text-justify:auto;text-orientation:mixed;text-overflow:clip;text-rendering:auto;text-shadow:none;text-transform:none;text-underline-position:auto;top:auto;touch-action:auto;transform:none;transform-box:borderBox;transform-origin:50% 50%0;transform-style:flat;transition-delay:0s;transition-duration:0s;transition-property:all;transition-timing-function:ease;vertical-align:baseline;visibility:visible;white-space:normal;widows:2;width:auto;will-change:auto;word-break:normal;word-spacing:normal;word-wrap:normal;writing-mode:horizontalTb;z-index:auto;-webkit-appearance:none;-moz-appearance:none;-ms-appearance:none;appearance:none;margin:0}.LiveAreaSection-193358632{width:100%}.LiveAreaSection-193358632 .login-option-buybox{display:block;width:100%;font-size:17px;line-height:30px;color:#222;padding-top:30px;font-family:Harding,Palatino,serif}.LiveAreaSection-193358632 .additional-access-options{display:block;font-weight:700;font-size:17px;line-height:30px;color:#222;font-family:Harding,Palatino,serif}.LiveAreaSection-193358632 .additional-login>li:not(:first-child)::before{transform:translateY(-50%);content:””;height:1rem;position:absolute;top:50%;left:0;border-left:2px solid #999}.LiveAreaSection-193358632 .additional-login>li:not(:first-child){padding-left:10px}.LiveAreaSection-193358632 .additional-login>li{display:inline-block;position:relative;vertical-align:middle;padding-right:10px}.BuyBoxSection-683559780{display:flex;flex-wrap:wrap;flex:1;flex-direction:row-reverse;margin:-30px -15px 0}.BuyBoxSection-683559780 .box-inner{width:100%;height:100%}.BuyBoxSection-683559780 .readcube-buybox{background-color:#f3f3f3;flex-shrink:1;flex-grow:1;flex-basis:255px;background-clip:content-box;padding:0 15px;margin-top:30px}.BuyBoxSection-683559780 .subscribe-buybox{background-color:#f3f3f3;flex-shrink:1;flex-grow:4;flex-basis:300px;background-clip:content-box;padding:0 15px;margin-top:30px}.BuyBoxSection-683559780 .subscribe-buybox-nature-plus{background-color:#f3f3f3;flex-shrink:1;flex-grow:4;flex-basis:100%;background-clip:content-box;padding:0 15px;margin-top:30px}.BuyBoxSection-683559780 .title-readcube,.BuyBoxSection-683559780 .title-buybox{display:block;margin:0;margin-right:10%;margin-left:10%;font-size:24px;line-height:32px;color:#222;padding-top:30px;text-align:center;font-family:Harding,Palatino,serif}.BuyBoxSection-683559780 .title-asia-buybox{display:block;margin:0;margin-right:5%;margin-left:5%;font-size:24px;line-height:32px;color:#222;padding-top:30px;text-align:center;font-family:Harding,Palatino,serif}.BuyBoxSection-683559780 .asia-link{color:#069;cursor:pointer;text-decoration:none;font-size:1.05em;font-family:-apple-system,BlinkMacSystemFont,”Segoe UI”,Roboto,Oxygen-Sans,Ubuntu,Cantarell,”Helvetica Neue”,sans-serif;line-height:1.05em6}.BuyBoxSection-683559780 .access-readcube{display:block;margin:0;margin-right:10%;margin-left:10%;font-size:14px;color:#222;padding-top:10px;text-align:center;font-family:-apple-system,BlinkMacSystemFont,”Segoe UI”,Roboto,Oxygen-Sans,Ubuntu,Cantarell,”Helvetica Neue”,sans-serif;line-height:20px}.BuyBoxSection-683559780 .access-asia-buybox{display:block;margin:0;margin-right:5%;margin-left:5%;font-size:14px;color:#222;padding-top:10px;text-align:center;font-family:-apple-system,BlinkMacSystemFont,”Segoe UI”,Roboto,Oxygen-Sans,Ubuntu,Cantarell,”Helvetica Neue”,sans-serif;line-height:20px}.BuyBoxSection-683559780 .access-buybox{display:block;margin:0;margin-right:10%;margin-left:10%;font-size:14px;color:#222;opacity:.8px;padding-top:10px;text-align:center;font-family:-apple-system,BlinkMacSystemFont,”Segoe UI”,Roboto,Oxygen-Sans,Ubuntu,Cantarell,”Helvetica Neue”,sans-serif;line-height:20px}.BuyBoxSection-683559780 .price-buybox{display:block;font-size:30px;color:#222;font-family:-apple-system,BlinkMacSystemFont,”Segoe UI”,Roboto,Oxygen-Sans,Ubuntu,Cantarell,”Helvetica Neue”,sans-serif;padding-top:30px;text-align:center}.BuyBoxSection-683559780 .price-buybox-to{display:block;font-size:30px;color:#222;font-family:-apple-system,BlinkMacSystemFont,”Segoe UI”,Roboto,Oxygen-Sans,Ubuntu,Cantarell,”Helvetica Neue”,sans-serif;text-align:center}.BuyBoxSection-683559780 .price-info-text{font-size:16px;padding-right:10px;color:#222;font-family:-apple-system,BlinkMacSystemFont,”Segoe UI”,Roboto,Oxygen-Sans,Ubuntu,Cantarell,”Helvetica Neue”,sans-serif}.BuyBoxSection-683559780 .price-value{font-size:30px;font-family:-apple-system,BlinkMacSystemFont,”Segoe UI”,Roboto,Oxygen-Sans,Ubuntu,Cantarell,”Helvetica Neue”,sans-serif}.BuyBoxSection-683559780 .price-per-period{font-family:-apple-system,BlinkMacSystemFont,”Segoe UI”,Roboto,Oxygen-Sans,Ubuntu,Cantarell,”Helvetica Neue”,sans-serif}.BuyBoxSection-683559780 .price-from{font-size:14px;padding-right:10px;color:#222;font-family:-apple-system,BlinkMacSystemFont,”Segoe UI”,Roboto,Oxygen-Sans,Ubuntu,Cantarell,”Helvetica Neue”,sans-serif;line-height:20px}.BuyBoxSection-683559780 .issue-buybox{display:block;font-size:13px;text-align:center;color:#222;font-family:-apple-system,BlinkMacSystemFont,”Segoe UI”,Roboto,Oxygen-Sans,Ubuntu,Cantarell,”Helvetica Neue”,sans-serif;line-height:19px}.BuyBoxSection-683559780 .no-price-buybox{display:block;font-size:13px;line-height:18px;text-align:center;padding-right:10%;padding-left:10%;padding-bottom:20px;padding-top:30px;color:#222;font-family:-apple-system,BlinkMacSystemFont,”Segoe UI”,Roboto,Oxygen-Sans,Ubuntu,Cantarell,”Helvetica Neue”,sans-serif}.BuyBoxSection-683559780 .vat-buybox{display:block;margin-top:5px;margin-right:20%;margin-left:20%;font-size:11px;color:#222;padding-top:10px;padding-bottom:15px;text-align:center;font-family:-apple-system,BlinkMacSystemFont,”Segoe UI”,Roboto,Oxygen-Sans,Ubuntu,Cantarell,”Helvetica Neue”,sans-serif;line-height:17px}.BuyBoxSection-683559780 .tax-buybox{display:block;width:100%;color:#222;padding:20px 16px;text-align:center;font-family:-apple-system,BlinkMacSystemFont,”Segoe UI”,Roboto,Oxygen-Sans,Ubuntu,Cantarell,”Helvetica Neue”,sans-serif;line-height:NaNpx}.BuyBoxSection-683559780 .button-container{display:flex;padding-right:20px;padding-left:20px;justify-content:center}.BuyBoxSection-683559780 .button-container>*{flex:1px}.BuyBoxSection-683559780 .button-container>a:hover,.Button-1078489254:hover,.Button-2496381730:hover{text-decoration:none}.BuyBoxSection-683559780 .readcube-button{background:#fff;margin-top:30px}.BuyBoxSection-683559780 .button-asia{background:#069;border:1px solid #069;border-radius:0;cursor:pointer;display:block;padding:9px;outline:0;text-align:center;text-decoration:none;min-width:80px;margin-top:75px}.BuyBoxSection-683559780 .button-label-asia,.ButtonLabel-3296148077,.ButtonLabel-1651148777{display:block;color:#fff;font-size:17px;line-height:20px;font-family:-apple-system,BlinkMacSystemFont,”Segoe UI”,Roboto,Oxygen-Sans,Ubuntu,Cantarell,”Helvetica Neue”,sans-serif;text-align:center;text-decoration:none;cursor:pointer}.Button-1078489254,.Button-2496381730{background:#069;border:1px solid #069;border-radius:0;cursor:pointer;display:block;padding:9px;outline:0;text-align:center;text-decoration:none;min-width:80px;max-width:320px;margin-top:10px}.Button-1078489254 .readcube-label,.Button-2496381730 .readcube-label{color:#069}
/* style specs end */

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. Wang H, Huang W, Fei Y-J, Xia H, Yang-Feng TL, Leibach FH, et al. Human placental Na+-dependent multivitamin transporter. J Biol Chem. 1999;274:14875–83.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  2. Baumgartner MR, Suormala T. Biotin-responsive Disorders. In: Inborn Metabolic Diseases. Springer Berlin Heidelberg. 2016. p. 375–83.

  3. Byrne AB, Arts P, Polyak SW, Feng J, Schreiber AW, Kassahn KS, et al. Identification and targeted management of a neurodegenerative disorder caused by biallelic mutations in SLC5A6. NPJ Genom Med. 2019;14:28.

    Article 

    Google Scholar 

  4. Hauth I, Waterham H, Wanders RJ, Van Der Crabben S, Van Karnebeek CD. A mild case of SMVT deficiency illustrating the importance of treatment response in variant classification. Mol Case Stud. 2022;8:a006185.

    Article 

    Google Scholar 

  5. Holling T, Nampoothiri S, Tarhan B, Schneeberger PE, Vinayan KP, Yesodharan D, et al. Novel biallelic variants expand the SLC5A6-related phenotypic spectrum. Eur J Hum Genet. 2022;30:439–49.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  6. Subramanian VS, Constantinescu AR, Benke PJ, Said HM. Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. Hum Genet. 2017;136:253–61.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  7. Schwantje M, De Sain-Van Der Velden M, Jans J, Van Gassen K, Dorrepaal C, Koop K, et al. Genetic defect of the sodium‐dependent multivitamin transporter: a treatable disease, mimicking biotinidase deficiency. JIMD Rep. 2019;48:11–14.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  8. Kameyama S, Mizuguchi T, Fukuda H, Moey LH, Keng WT, Okamoto N, et al. Biallelic null variants in ZNF142 cause global developmental delay with familial epilepsy and dysmorphic features. J Hum Genet. 2022;67:169–73.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  9. Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38:e164.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

  10. Ng PC. SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003;31:3812–14.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  11. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7:248–9.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  12. Steinhaus R, Proft S, Schuelke M, Cooper DN, Schwarz Jana M, Seelow D. MutationTaster2021. Nucleic Acids Res. 2021;49:W446–51.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  13. Kircher M, Witten DM, Jain P, O’Roak BJ, Cooper GM, Shendure J. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet. 2014;46:310–15.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  14. Ioannidis NM, Rothstein JH, Pejaver V, Middha S, McDonnell SK, Baheti S, et al. REVEL: an ensemble method for predicting the pathogenicity of rare missense variants. Am J Hum Genet. 2016;99:877–85.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  15. Capriotti E, Altman RB, Bromberg Y. Collective judgment predicts disease-associated single nucleotide variants. BMC Genom. 2013;14:S2.

    Article 

    Google Scholar 

  16. Danzi MC, Dohrn MF, Fazal S, Beijer D, Rebelo AP, Cintra V, et al. Deep structured learning for variant prioritization in Mendelian diseases. Nat Commun. 2023;14:4167.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  17. Cheng J, Novati G, Pan J, Bycroft C, Žemgulytė A, Applebaum T, et al. Accurate proteome-wide missense variant effect prediction with AlphaMissense. Science. 2023;381:eadg7492.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  18. Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994;22:4673–80.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  19. Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596:583–89.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  20. Guerois R, Nielsen JE, Serrano L. Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations. J Mol Biol. 2002;320:369–87.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  21. Schymkowitz J, Borg J, Stricher F, Nys R, Rousseau F, Serrano L. The FoldX web server: an online force field. Nucleic Acids Res. 2005;33:W382–8.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  22. Kondo S, Ueda R. Highly improved gene targeting by germline-specific Cas9 expression in drosophila. Genetics. 2013;195:715–21.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  23. Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alföldi J, Wang Q, et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature. 2020;581:434–43.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  24. Tadaka S, Hishinuma E, Komaki S, Motoike IN, Kawashima J, Saigusa D, et al. jMorp updates in 2020: large enhancement of multi-omics data resources on the general Japanese population. Nucleic Acids Res. 2021;49:D536–D44.

    Article 
    CAS 
    PubMed 

    Google Scholar 

  25. Gerasimavicius L, Liu X, Marsh JA. Identification of pathogenic missense mutations using protein stability predictors. Sci Rep. 2020;10:15387.

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar 

  26. Bromberg Y, Rost B. Correlating protein function and stability through the analysis of single amino acid substitutions. BMC Bioinforma. 2009;10:S8.

    Article 

    Google Scholar 

  27. Institute of Medicine Standing Committee on the Scientific Evaluation of Dietary Reference I, its Panel on Folate OBV, Choline. The National Academies Collection: Reports funded by National Institutes of Health. In: Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B(6), Folate, Vitamin B(12), Pantothenic Acid, Biotin, and Choline. Washington (DC): National Academies Press (US)Copyright © 1998, National Academy of Sciences.; 1998.

  28. Tokutomi T, Fukushima A, Yamamoto K, Bansho Y, Hachiya T, Shimizu A. f-treeGC: a questionnaire-based family tree-creation software for genetic counseling and genome cohort studies. BMC Med Genet. 2017;18:71.

    Article 
    PubMed 
    PubMed Central 

    Google Scholar 

Download references

Acknowledgements

We thank the participants for their cooperation. We also thank Ms. K. Takabe, Mr. T. Miyama, Ms. N. Watanabe, Ms. M. Sato, and Ms. S. Sugimoto at the Department of Human Genetics, Yokohama City University Graduate School of Medicine, for their technical assistance. We also thank Jeremy Allen, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This work was supported by the Japan Agency for Medical Research and Development (AMED) under grant numbers JP23ek0109674, JP23ek0109549, JP23ek0109617 and JP23ek0109648 (N. Matsumoto); JSPS KAKENHI under grant numbers JP23H02829 (S. Miyatake), JP23K15353 (E. Koshimizu), JP22K15646 (K. Hamanaka), JP22K15901 (A. Fujita), JP23K07229 (Y. Uchiyama), JP23K15353 (N. Tsuchida), and JP23H02877 (T. Mizuguchi); the Takeda Science Foundation (T. Mizuguchi, and N. Matsumoto).

Author information

Authors and Affiliations

  1. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Yasuhiro Utsuno, Kohei Hamanaka, Toshiyuki Itai, Masamune Sakamoto, Naomi Tsuchida, Yuri Uchiyama, Eriko Koshimizu, Atsushi Fujita, Satoko Miyatake, Kazuharu Misawa, Takeshi Mizuguchi & Naomichi Matsumoto

  2. Department of Obstetrics and Gynecology, Asahikawa Medical University, Hokkaido, Japan

    Yasuhiro Utsuno & Yasuhito Kato

  3. Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Keisuke Hamada & Kazuhiro Ogata

  4. Department of Chromosome Science, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Shizuoka, Japan

    Keita Miyoshi & Kuniaki Saito

  5. Graduate Institute for Advanced Studies, SOKENDAI, Shizuoka, Japan

    Keita Miyoshi & Kuniaki Saito

  6. Department of Pediatrics, Kochi Health Sciences Center, Kochi, Japan

    Keiji Tsuchimoto

  7. Department of Pediatrics, Kurashiki Central Hospital, Okayama, Japan

    Satoshi Sunada

  8. Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Japan

    Masamune Sakamoto, Naomi Tsuchida & Yuri Uchiyama

  9. Department of Clinical Genetics, Yokohama City University Hospital, Yokohama, Japan

    Satoko Miyatake

  10. RIKEN Center for Advanced Intelligence Project, Tokyo, Japan

    Kazuharu Misawa

Authors

  1. Yasuhiro Utsuno
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  2. Keisuke Hamada
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  3. Kohei Hamanaka
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  4. Keita Miyoshi
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  5. Keiji Tsuchimoto
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  6. Satoshi Sunada
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  7. Toshiyuki Itai
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  8. Masamune Sakamoto
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  9. Naomi Tsuchida
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  10. Yuri Uchiyama
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  11. Eriko Koshimizu
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  12. Atsushi Fujita
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  13. Satoko Miyatake
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  14. Kazuharu Misawa
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  15. Takeshi Mizuguchi
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  16. Yasuhito Kato
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  17. Kuniaki Saito
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  18. Kazuhiro Ogata
    View author publications

    You can also search for this author in
    PubMed Google Scholar

  19. Naomichi Matsumoto
    View author publications

    You can also search for this author in
    PubMed Google Scholar

Corresponding author

Correspondence to
Naomichi Matsumoto.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

README

Supplementary Table 1

Supplementary Table 2

Supplementary Table 3

Supplementary Table 4

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Utsuno, Y., Hamada, K., Hamanaka, K. et al. Novel missense variants cause intermediate phenotypes in the phenotypic spectrum of SLC5A6-related disorders.
J Hum Genet (2023). https://doi.org/10.1038/s10038-023-01206-5

Download citation

  • Received: 23 January 2023

  • Revised: 05 November 2023

  • Accepted: 05 November 2023

  • Published: 27 November 2023

  • DOI: https://doi.org/10.1038/s10038-023-01206-5

yun

Leave a Reply

Your email address will not be published. Required fields are marked *