Genetic enhancement of cognition in a kindred with cone-rod dystrophy due to RIMS1 mutation

Sanjay M. Sisodiya; Pamela J. Thompson; Anna Need; Sarah E. Harris; Michael E. Weale; Susan E. Wilkie; Michel Michaelides; Samantha L. Free; Nicole Walley; Curtis Gumbs; Dianne Gerrelli; Piers Ruddle; Lawrence J. Whalley; John Starr; David M. Hunt; David B. Goldstein; Ian J. Deary; Anthony T. Moore

doi:10.1136/jmg.2006.047407

Genetic enhancement of cognition in a kindred with cone-rod dystrophy due to RIMS1 mutation

Sanjay M. Sisodiya, Pamela J. Thompson, Anna Need, Sarah E. Harris, Michael E. Weale, Susan E. Wilkie, Michel Michaelides, Samantha L. Free, Nicole Walley, Curtis Gumbs, Dianne Gerrelli, Piers Ruddle, Lawrence J. Whalley, John Starr, David M. Hunt, David B. Goldstein, Ian J. Deary, Anthony T. Moore

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Background: The genetic basis of variation in human cognitive abilities is poorly understood. RIMS1 encodes a synapse active- zone protein with important roles in the maintenance of normal synaptic function: mice lacking this protein have greatly reduced learning ability and memory function.

Objective: An established paradigm examining the structural and functional effects of mutations in genes expressed in the eye and the brain was used to study a kindred with an inherited retinal dystrophy due to RIMS1 mutation.

Materials and methods: Neuropsychological tests and high- resolution MRI brain scanning were undertaken in the kindred. In a population cohort, neuropsychological scores were associated with common variation in RIMS1. Additionally, RIMS1 was sequenced in top- scoring individuals. Evolution of RIMS1 was assessed, and its expression in developing human brain was studied.

Results: Affected individuals showed significantly enhanced cognitive abilities across a range of domains. Analysis suggests that factors other than RIMS1 mutation were unlikely to explain enhanced cognition. No association with common variation and verbal IQ was found in the population cohort, and no other mutations in RIMS1 were detected in the highest scoring individuals from this cohort. RIMS1 protein is expressed in developing human brain, but RIMS1 does not seem to have been subjected to accelerated evolution in man.

Conclusions: A possible role for RIMS1 in the enhancement of cognitive function at least in this kindred is suggested. Although further work is clearly required to explore these findings before a role for RIMS1 in human cognition can be formally accepted, the findings suggest that genetic mutation may enhance human cognition in some cases.

Original language	English
Pages (from-to)	373-380
Number of pages	8
Journal	The American Journal of Medical Genetics - Part A (AJMG)
Volume	44
Issue number	6
DOIs	https://doi.org/10.1136/jmg.2006.047407
Publication status	Published - Jun 2007

Keywords / Materials (for Non-textual outputs)

PARKINSONS-DISEASE
HOMO-SAPIENS
ACTIVE ZONE
BRAIN SIZE
RIM1-ALPHA
HUMANS
CORD7
MALFORMATIONS
EVOLUTION
PINK1

Access to Document

10.1136/jmg.2006.047407

Age-related cognitive changes in healthy humans: influences from genetic variation in genes related to oxidative stress
Deary, I. & Starr, J.
BBSRC
1/03/03 → 31/03/10
Project: Research

Cite this

Sisodiya, S. M., Thompson, P. J., Need, A., Harris, S. E., Weale, M. E., Wilkie, S. E., Michaelides, M., Free, S. L., Walley, N., Gumbs, C., Gerrelli, D., Ruddle, P., Whalley, L. J., Starr, J., Hunt, D. M., Goldstein, D. B., Deary, I. J., & Moore, A. T. (2007). Genetic enhancement of cognition in a kindred with cone-rod dystrophy due to RIMS1 mutation. The American Journal of Medical Genetics - Part A (AJMG), 44(6), 373-380. https://doi.org/10.1136/jmg.2006.047407

@article{ad9fec6fab484be6b33b3e1a90f4da3e,

title = "Genetic enhancement of cognition in a kindred with cone-rod dystrophy due to RIMS1 mutation",

abstract = "Background: The genetic basis of variation in human cognitive abilities is poorly understood. RIMS1 encodes a synapse active- zone protein with important roles in the maintenance of normal synaptic function: mice lacking this protein have greatly reduced learning ability and memory function.Objective: An established paradigm examining the structural and functional effects of mutations in genes expressed in the eye and the brain was used to study a kindred with an inherited retinal dystrophy due to RIMS1 mutation.Materials and methods: Neuropsychological tests and high- resolution MRI brain scanning were undertaken in the kindred. In a population cohort, neuropsychological scores were associated with common variation in RIMS1. Additionally, RIMS1 was sequenced in top- scoring individuals. Evolution of RIMS1 was assessed, and its expression in developing human brain was studied.Results: Affected individuals showed significantly enhanced cognitive abilities across a range of domains. Analysis suggests that factors other than RIMS1 mutation were unlikely to explain enhanced cognition. No association with common variation and verbal IQ was found in the population cohort, and no other mutations in RIMS1 were detected in the highest scoring individuals from this cohort. RIMS1 protein is expressed in developing human brain, but RIMS1 does not seem to have been subjected to accelerated evolution in man.Conclusions: A possible role for RIMS1 in the enhancement of cognitive function at least in this kindred is suggested. Although further work is clearly required to explore these findings before a role for RIMS1 in human cognition can be formally accepted, the findings suggest that genetic mutation may enhance human cognition in some cases.",

keywords = "PARKINSONS-DISEASE, HOMO-SAPIENS, ACTIVE ZONE, BRAIN SIZE, RIM1-ALPHA, HUMANS, CORD7, MALFORMATIONS, EVOLUTION, PINK1",

author = "Sisodiya, {Sanjay M.} and Thompson, {Pamela J.} and Anna Need and Harris, {Sarah E.} and Weale, {Michael E.} and Wilkie, {Susan E.} and Michel Michaelides and Free, {Samantha L.} and Nicole Walley and Curtis Gumbs and Dianne Gerrelli and Piers Ruddle and Whalley, {Lawrence J.} and John Starr and Hunt, {David M.} and Goldstein, {David B.} and Deary, {Ian J.} and Moore, {Anthony T.}",

year = "2007",

month = jun,

doi = "10.1136/jmg.2006.047407",

language = "English",

volume = "44",

pages = "373--380",

journal = "The American Journal of Medical Genetics - Part A (AJMG)",

issn = "1552-4825",

publisher = "Wiley",

number = "6",

}

Sisodiya, SM, Thompson, PJ, Need, A, Harris, SE, Weale, ME, Wilkie, SE, Michaelides, M, Free, SL, Walley, N, Gumbs, C, Gerrelli, D, Ruddle, P, Whalley, LJ, Starr, J, Hunt, DM, Goldstein, DB, Deary, IJ & Moore, AT 2007, 'Genetic enhancement of cognition in a kindred with cone-rod dystrophy due to RIMS1 mutation', The American Journal of Medical Genetics - Part A (AJMG), vol. 44, no. 6, pp. 373-380. https://doi.org/10.1136/jmg.2006.047407

TY - JOUR

T1 - Genetic enhancement of cognition in a kindred with cone-rod dystrophy due to RIMS1 mutation

AU - Sisodiya, Sanjay M.

AU - Thompson, Pamela J.

AU - Need, Anna

AU - Harris, Sarah E.

AU - Weale, Michael E.

AU - Wilkie, Susan E.

AU - Michaelides, Michel

AU - Free, Samantha L.

AU - Walley, Nicole

AU - Gumbs, Curtis

AU - Gerrelli, Dianne

AU - Ruddle, Piers

AU - Whalley, Lawrence J.

AU - Starr, John

AU - Hunt, David M.

AU - Goldstein, David B.

AU - Deary, Ian J.

AU - Moore, Anthony T.

PY - 2007/6

Y1 - 2007/6

N2 - Background: The genetic basis of variation in human cognitive abilities is poorly understood. RIMS1 encodes a synapse active- zone protein with important roles in the maintenance of normal synaptic function: mice lacking this protein have greatly reduced learning ability and memory function.Objective: An established paradigm examining the structural and functional effects of mutations in genes expressed in the eye and the brain was used to study a kindred with an inherited retinal dystrophy due to RIMS1 mutation.Materials and methods: Neuropsychological tests and high- resolution MRI brain scanning were undertaken in the kindred. In a population cohort, neuropsychological scores were associated with common variation in RIMS1. Additionally, RIMS1 was sequenced in top- scoring individuals. Evolution of RIMS1 was assessed, and its expression in developing human brain was studied.Results: Affected individuals showed significantly enhanced cognitive abilities across a range of domains. Analysis suggests that factors other than RIMS1 mutation were unlikely to explain enhanced cognition. No association with common variation and verbal IQ was found in the population cohort, and no other mutations in RIMS1 were detected in the highest scoring individuals from this cohort. RIMS1 protein is expressed in developing human brain, but RIMS1 does not seem to have been subjected to accelerated evolution in man.Conclusions: A possible role for RIMS1 in the enhancement of cognitive function at least in this kindred is suggested. Although further work is clearly required to explore these findings before a role for RIMS1 in human cognition can be formally accepted, the findings suggest that genetic mutation may enhance human cognition in some cases.

AB - Background: The genetic basis of variation in human cognitive abilities is poorly understood. RIMS1 encodes a synapse active- zone protein with important roles in the maintenance of normal synaptic function: mice lacking this protein have greatly reduced learning ability and memory function.Objective: An established paradigm examining the structural and functional effects of mutations in genes expressed in the eye and the brain was used to study a kindred with an inherited retinal dystrophy due to RIMS1 mutation.Materials and methods: Neuropsychological tests and high- resolution MRI brain scanning were undertaken in the kindred. In a population cohort, neuropsychological scores were associated with common variation in RIMS1. Additionally, RIMS1 was sequenced in top- scoring individuals. Evolution of RIMS1 was assessed, and its expression in developing human brain was studied.Results: Affected individuals showed significantly enhanced cognitive abilities across a range of domains. Analysis suggests that factors other than RIMS1 mutation were unlikely to explain enhanced cognition. No association with common variation and verbal IQ was found in the population cohort, and no other mutations in RIMS1 were detected in the highest scoring individuals from this cohort. RIMS1 protein is expressed in developing human brain, but RIMS1 does not seem to have been subjected to accelerated evolution in man.Conclusions: A possible role for RIMS1 in the enhancement of cognitive function at least in this kindred is suggested. Although further work is clearly required to explore these findings before a role for RIMS1 in human cognition can be formally accepted, the findings suggest that genetic mutation may enhance human cognition in some cases.

KW - PARKINSONS-DISEASE

KW - HOMO-SAPIENS

KW - ACTIVE ZONE

KW - BRAIN SIZE

KW - RIM1-ALPHA

KW - HUMANS

KW - CORD7

KW - MALFORMATIONS

KW - EVOLUTION

KW - PINK1

U2 - 10.1136/jmg.2006.047407

DO - 10.1136/jmg.2006.047407

M3 - Article

SN - 1552-4825

VL - 44

SP - 373

EP - 380

JO - The American Journal of Medical Genetics - Part A (AJMG)

JF - The American Journal of Medical Genetics - Part A (AJMG)

IS - 6

ER -

Genetic enhancement of cognition in a kindred with cone-rod dystrophy due to RIMS1 mutation

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Keywords / Materials (for Non-textual outputs)

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Age-related cognitive changes in healthy humans: influences from genetic variation in genes related to oxidative stress

Cite this