Mutations in the Histamine N-Methyltransferase Gene, Hnmt, Are Associated With Nonsyndromic Autosomal Recessive Intellectual Disability

Mutations in the Histamine N-Methyltransferase Gene, Hnmt, Are Associated With Nonsyndromic Autosomal Recessive Intellectual Disability Publisher Pubmed

Heidari A^{1, 2} ; Tongsook C⁴ ; Najafipour R² ; Musante L⁵ ; Vasli N¹ ; Garshasbi M^{5, 6} ; Hu H⁵ ; Mittal K¹ ; Mcnaughton AJM⁷ ; Sritharan K¹ ; Hudson M⁷ ; Stehr H⁹ ; Talebi S¹⁰ ; Moradi M² Show All Authors

Heidari A^{1, 2}
Tongsook C⁴
Najafipour R²
Musante L⁵
Vasli N¹
Garshasbi M^{5, 6}
Hu H⁵
Mittal K¹
Mcnaughton AJM⁷
Sritharan K¹
Hudson M⁷
Stehr H⁹
Talebi S¹⁰
Moradi M²
Darvish H¹¹
Rafiq MA¹
Mozhdehipanah H³
Rashidinejad A¹²
Samiei S¹³
Ghadami M¹⁴
Windpassinger C¹⁵
Gillessenkaesbach G¹⁶
Tzschach A^{5, 24}
Ahmed I^{1, 17}
Mikhailov A¹
James Stavropoulos D¹⁸
Carter MT¹⁹
Keshavarz S²
Ayub M⁸
Najmabadi H^{20, 21}
Liu X⁷
Ropers HH⁵
Macheroux P⁴
Vincent JB^{1, 22, 23}

Source: Human Molecular Genetics Published:2015

Abstract

Histamine (HA) acts as a neurotransmitter in the brain,which participates in the regulation ofmany biological processes including inflammation, gastric acid secretionand neuromodulation. The enzyme histamineN-methyltransferase (HNMT) inactivatesHAby transferring a methyl group from S-adenosyl-?-methionine to HA, and is the only well-known pathway for termination of neurotransmission actions of HA in mammalian central nervous system. We performed autozygosity mapping followed by targeted exome sequencing and identified two homozygous HNMT alterations, p.Gly60Asp and p.Leu208Pro, in patients affected with nonsyndromic autosomal recessive intellectual disability from two unrelated consanguineous families of Turkish and Kurdish ancestry, respectively. We verified the complete absence of a functional HNMT in patients using in vitro toxicology assay. Using mutant and wild-type DNA constructs as well as in silico protein modeling, we confirmed that p.Gly60Asp disrupts the enzymatic activity of the protein, and that p.Leu208Pro results in reduced protein stability, resulting in decreased HA inactivation. Our results highlight the importance of inclusion of HNMT for genetic testing of individuals presentingwith intellectual disability. © The Author 2015.

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Style	Citing Format
MLA	Heidari A, et al.. "Mutations in the Histamine N-Methyltransferase Gene, Hnmt, Are Associated With Nonsyndromic Autosomal Recessive Intellectual Disability." Human Molecular Genetics, vol. 24, no. 20, 2015, pp. 5697-5710.
APA	Heidari A, Tongsook C, Najafipour R, Musante L, Vasli N, Garshasbi M, Hu H, Mittal K, Mcnaughton AJM, Sritharan K, Hudson M, Stehr H, Talebi S, Moradi M, Darvish H, Rafiq MA, Mozhdehipanah H, Rashidinejad A, Samiei S, ... Vincent JB (2015). Mutations in the Histamine N-Methyltransferase Gene, Hnmt, Are Associated With Nonsyndromic Autosomal Recessive Intellectual Disability. Human Molecular Genetics, 24(20), 5697-5710.
Chicago	Heidari A, Tongsook C, Najafipour R, Musante L, Vasli N, Garshasbi M, Hu H, et al.. "Mutations in the Histamine N-Methyltransferase Gene, Hnmt, Are Associated With Nonsyndromic Autosomal Recessive Intellectual Disability." Human Molecular Genetics 24, no. 20 (2015): 5697-5710.
Harvard	Heidari A et al. (2015) 'Mutations in the Histamine N-Methyltransferase Gene, Hnmt, Are Associated With Nonsyndromic Autosomal Recessive Intellectual Disability', Human Molecular Genetics, 24(20), pp. 5697-5710.
Vancouver	Heidari A, Tongsook C, Najafipour R, Musante L, Vasli N, Garshasbi M, et al.. Mutations in the Histamine N-Methyltransferase Gene, Hnmt, Are Associated With Nonsyndromic Autosomal Recessive Intellectual Disability. Human Molecular Genetics. 2015;24(20):5697-5710.
BibTex	@article{ author = {Heidari A and Tongsook C and Najafipour R and Musante L and Vasli N and Garshasbi M and Hu H and Mittal K and Mcnaughton AJM and Sritharan K and Hudson M and Stehr H and Talebi S and Moradi M and Darvish H and Rafiq MA and Mozhdehipanah H and Rashidinejad A and Samiei S and Ghadami M and Windpassinger C and Gillessenkaesbach G and Tzschach A and Ahmed I and Mikhailov A and James Stavropoulos D and Carter MT and Keshavarz S and Ayub M and Najmabadi H and Liu X and Ropers HH and Macheroux P and Vincent JB}, title = {Mutations in the Histamine N-Methyltransferase Gene, Hnmt, Are Associated With Nonsyndromic Autosomal Recessive Intellectual Disability}, journal = {Human Molecular Genetics}, volume = {24}, number = {20}, pages = {5697-5710}, year = {2015} }
RIS	TY - JOUR AU - Heidari A AU - Tongsook C AU - Najafipour R AU - Musante L AU - Vasli N AU - Garshasbi M AU - Hu H AU - Mittal K AU - Mcnaughton AJM AU - Sritharan K AU - Hudson M AU - Stehr H AU - Talebi S AU - Moradi M AU - Darvish H AU - Rafiq MA AU - Mozhdehipanah H AU - Rashidinejad A AU - Samiei S AU - Ghadami M AU - Windpassinger C AU - Gillessenkaesbach G AU - Tzschach A AU - Ahmed I AU - Mikhailov A AU - James Stavropoulos D AU - Carter MT AU - Keshavarz S AU - Ayub M AU - Najmabadi H AU - Liu X AU - Ropers HH AU - Macheroux P AU - Vincent JB TI - Mutations in the Histamine N-Methyltransferase Gene, Hnmt, Are Associated With Nonsyndromic Autosomal Recessive Intellectual Disability JO - Human Molecular Genetics VL - 24 IS - 20 SP - 5697 EP - 5710 PY - 2015 ER -

Style

Citing Format

MLA

Heidari A, et al.. "Mutations in the Histamine N-Methyltransferase Gene, Hnmt, Are Associated With Nonsyndromic Autosomal Recessive Intellectual Disability." Human Molecular Genetics, vol. 24, no. 20, 2015, pp. 5697-5710.

APA

Heidari A, Tongsook C, Najafipour R, Musante L, Vasli N, Garshasbi M, Hu H, Mittal K, Mcnaughton AJM, Sritharan K, Hudson M, Stehr H, Talebi S, Moradi M, Darvish H, Rafiq MA, Mozhdehipanah H, Rashidinejad A, Samiei S, ... Vincent JB (2015). Mutations in the Histamine N-Methyltransferase Gene, Hnmt, Are Associated With Nonsyndromic Autosomal Recessive Intellectual Disability. Human Molecular Genetics, 24(20), 5697-5710.

Chicago

Heidari A, Tongsook C, Najafipour R, Musante L, Vasli N, Garshasbi M, Hu H, et al.. "Mutations in the Histamine N-Methyltransferase Gene, Hnmt, Are Associated With Nonsyndromic Autosomal Recessive Intellectual Disability." Human Molecular Genetics 24, no. 20 (2015): 5697-5710.

Harvard

Heidari A et al. (2015) 'Mutations in the Histamine N-Methyltransferase Gene, Hnmt, Are Associated With Nonsyndromic Autosomal Recessive Intellectual Disability', Human Molecular Genetics, 24(20), pp. 5697-5710.

Vancouver

Heidari A, Tongsook C, Najafipour R, Musante L, Vasli N, Garshasbi M, et al.. Mutations in the Histamine N-Methyltransferase Gene, Hnmt, Are Associated With Nonsyndromic Autosomal Recessive Intellectual Disability. Human Molecular Genetics. 2015;24(20):5697-5710.

BibTex

@article{ author = {Heidari A and Tongsook C and Najafipour R and Musante L and Vasli N and Garshasbi M and Hu H and Mittal K and Mcnaughton AJM and Sritharan K and Hudson M and Stehr H and Talebi S and Moradi M and Darvish H and Rafiq MA and Mozhdehipanah H and Rashidinejad A and Samiei S and Ghadami M and Windpassinger C and Gillessenkaesbach G and Tzschach A and Ahmed I and Mikhailov A and James Stavropoulos D and Carter MT and Keshavarz S and Ayub M and Najmabadi H and Liu X and Ropers HH and Macheroux P and Vincent JB}, title = {Mutations in the Histamine N-Methyltransferase Gene, Hnmt, Are Associated With Nonsyndromic Autosomal Recessive Intellectual Disability}, journal = {Human Molecular Genetics}, volume = {24}, number = {20}, pages = {5697-5710}, year = {2015} }

RIS

TY - JOUR
AU - Heidari A
AU - Tongsook C
AU - Najafipour R
AU - Musante L
AU - Vasli N
AU - Garshasbi M
AU - Hu H
AU - Mittal K
AU - Mcnaughton AJM
AU - Sritharan K
AU - Hudson M
AU - Stehr H
AU - Talebi S
AU - Moradi M
AU - Darvish H
AU - Rafiq MA
AU - Mozhdehipanah H
AU - Rashidinejad A
AU - Samiei S
AU - Ghadami M
AU - Windpassinger C
AU - Gillessenkaesbach G
AU - Tzschach A
AU - Ahmed I
AU - Mikhailov A
AU - James Stavropoulos D
AU - Carter MT
AU - Keshavarz S
AU - Ayub M
AU - Najmabadi H
AU - Liu X
AU - Ropers HH
AU - Macheroux P
AU - Vincent JB
TI - Mutations in the Histamine N-Methyltransferase Gene, Hnmt, Are Associated With Nonsyndromic Autosomal Recessive Intellectual Disability
JO - Human Molecular Genetics
VL - 24
IS - 20
SP - 5697
EP - 5710
PY - 2015
ER -

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Abstract