1. Volume 148, Issue 3, Pages 533-536.e4 (March 2015)
Truncating Mutation in the Nitric Oxide Synthase 1 Gene Is Associated With Infantile Achalasia 
Eyal Shteyer, Simon Edvardson, Sarah L. Wynia-Smith, Ciro Leonardo Pierri, Tzili Zangen, Saar Hashavya, Michal Begin, Barak Yaacov, Yuval Cinamon, Benjamin Z. Koplewitz, Amos Vromen, Orly Elpeleg, Brian C. Smith 
Gastroenterology 
Volume 148, Issue 3, Pages e4 (March 2015)
DOI: /j.gastro
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2. Figure 1
(A) Family pedigree, patients are designated by filled symbols and the mutation genotype is indicated (B). NOS1 genomic sequence around the mutation site in the DNA samples of the family members, and of a normal control (C). An upper gastrointestinal series (D) and a high-resolution manometry (E) of patient II-1. There is severe narrowing (arrow) of the distal esophagus (Eso). High-resolution manometry (E) after 5-mL water swallow shows premature spastic contraction (distal latency 3.8 s) and impaired lower esophageal sphincter relaxation (integrated relaxation pressure [IRP] of 36 mmHg), exhibited in 6 of 10 swallows, compatible with type III achalasia.
Gastroenterology  , e4DOI: ( /j.gastro )
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3. Figure 2
(A) Representative scheme of the NOS1 domains and overall structure of NOSred module. (B) Amino acid alignment. The tyrosine in position 1202, mutated in our patients, is highly conserved in the NOS1 orthologs. (C) Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of purified rat nNOS WT and Y1197X. Proteins were visualized using Bio-Rad Stain Free technology. The positioning of the molecular weight (MW) standards is shown on the left. (D) Rates of NO formation and NADPH oxidation for rat nNOS WT (gray) and Y1197X (red) (equivalent to Y1202X in human nNOS). Rates were determined as detailed in the Supplementary Material. ND, not detectable. (E) 3-Dimensional structure of NOSred domain is reported in cartoon representation. Y1202 is reported in magenta sticks. The position of the Y1202X mutation is indicated by a “STOP” sign. The region highlighted in the red cartoon indicates the truncated NOSred portion that in the WT NOS1 protein participates in binding of the NADPH and FAD cofactors. FMN, NADPH, and FAD are indicated by violet, yellow, and cyan sticks, respectively. NOSox, nitric oxide synthase N-terminal catalytic oxidase module; PDZ, PDZ domain.
Gastroenterology  , e4DOI: ( /j.gastro )
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