دورية أكاديمية
أعرض في EDS

Mutations in SPINT2 cause a syndromic form of congenital sodium diarrhea.

التفاصيل البيبلوغرافية
العنوان: Mutations in SPINT2 cause a syndromic form of congenital sodium diarrhea.
المؤلفون: Heinz-Erian P; Department of Pediatrics II, Innsbruck Medical University, A-6020 Innsbruck, Austria., Müller T, Krabichler B, Schranz M, Becker C, Rüschendorf F, Nürnberg P, Rossier B, Vujic M, Booth IW, Holmberg C, Wijmenga C, Grigelioniene G, Kneepkens CM, Rosipal S, Mistrik M, Kappler M, Michaud L, Dóczy LC, Siu VM, Krantz M, Zoller H, Utermann G, Janecke AR
المصدر: American journal of human genetics [Am J Hum Genet] 2009 Feb; Vol. 84 (2), pp. 188-96. Date of Electronic Publication: 2009 Jan 29.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 0370475 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1537-6605 (Electronic) Linking ISSN: 00029297 NLM ISO Abbreviation: Am J Hum Genet Subsets: MEDLINE
أسماء مطبوعة: Publication: 2008- : [Cambridge, MA] : Cell Press
Original Publication: Baltimore, American Society of Human Genetics.
مواضيع طبية MeSH: Mutation*, Diarrhea/*genetics , Malabsorption Syndromes/*genetics , Membrane Glycoproteins/*genetics , Sodium/*metabolism, Amino Acid Sequence ; Anus, Imperforate/genetics ; Anus, Imperforate/mortality ; Anus, Imperforate/pathology ; Base Sequence ; Chromosome Mapping ; Cohort Studies ; DNA Mutational Analysis ; Diarrhea/mortality ; Diarrhea/pathology ; Feces/chemistry ; Female ; Genes, Recessive ; Humans ; Infant ; Infant, Newborn ; Malabsorption Syndromes/mortality ; Malabsorption Syndromes/pathology ; Male ; Molecular Sequence Data ; Pedigree ; RNA, Messenger/genetics ; Survival Analysis
مستخلص: Autosomal-recessive congenital sodium diarrhea (CSD) is characterized by perinatal onset of a persistent watery diarrhea with nonproportionally high fecal sodium excretion. Defective jejunal brush-border Na(+)/H(+) exchange has been reported in three sporadic patients, but the molecular basis of the disease has not been elucidated. We reviewed data from a large cohort of CSD patients (n = 24) and distinguished CSD associated with choanal or anal atresia, hypertelorism, and corneal erosions--i.e., a syndromic form of CSD--occurring in ten families from an isolated form--i.e., classic CSD--presenting in seven families. Patients from both groups have a high risk of mortality due to immediate electrolyte imbalances and complications from long-term parenteral nutrition in the first years of life, but survivors can eventually adapt to partial or complete enteral nutrition. A genome-wide SNP scan was applied and identified a homozygous c.593-1G-->A splicing mutation in SPINT2, encoding a Kunitz-type serine-protease inhibitor, in one extended kindred with syndromic CSD. The same mutation and four distinct, homozygous or compound heterozygous mutations (p.Y163C, c.1A-->T, c.337+2T-->C, c.553+2T-->A) were identified in all syndromic patients. No SPINT2 mutations were found in classic-CSD patients. SPINT2 mutations were associated with loss of protein synthesis or failure to inhibit the serine protease trypsin in vitro. We delineate syndromic CSD as a distinct disease entity caused by SPINT2 loss-of-function mutations. SPINT2 mutations might lead to an excess of yet unknown serine protease activity in affected tissues.
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المشرفين على المادة: 0 (Membrane Glycoproteins)
0 (RNA, Messenger)
0 (SPINT2 protein, human)
9NEZ333N27 (Sodium)
تواريخ الأحداث: Date Created: 20090203 Date Completed: 20090323 Latest Revision: 20211020
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC2668003
DOI: 10.1016/j.ajhg.2009.01.004
PMID: 19185281
قاعدة البيانات: MEDLINE
الوصف
تدمد:1537-6605
DOI:10.1016/j.ajhg.2009.01.004