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Potential oligogenic disease of mental retardation, short stature, spastic paraparesis and osteopetrosis

Authors Alsemari A, Alsuhaibani M, Alhathlool R, Ali BM

Received 24 April 2018

Accepted for publication 1 August 2018

Published 8 November 2018 Volume 2018:11 Pages 129—134


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Martin H. Maurer

Abdulaziz Alsemari,1 Mohanned Alsuhaibani,2 Rawabi Alhathlool,1 Bayan Mamdouh Ali1

1Department of Neurosciences, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; 2Department of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Abstract: The interaction of multiple genetic factors, as opposed to monogenic inheritance, has been suspected to play a role in many diseases. This interaction has been described as an oligogenic inheritance model, which may be a useful tool in explaining certain clinical observations. The purpose of this study was to search for novel genetic defects among members of a family with traits that include mental retardation, short stature, osteopetrosis, calcification of basal ganglia, and thinning of the corpus callosum. In the index case (111-4), we identified four homozygous mutations: chromosome 8, intron2 (c.232+1G>A) at CA2 gene; chromosome 15, exon 32 (c.6100C>T) at the SPG11; chromosome 5, exon 11 (c.1015G>A) at the MCCC2; and chromosome 9, exon 9 (C.1193g>t) at the LARP gene. The mutations were confirmed by Sanger sequencing, and both parents were observed to be heterozygous for the four mutations. A moderately affected sister of the index case was homozygous for only three mutations in CA2, LARP, and Mccc2, while a nonaffected sister was heterozygous for three mutations in CA2, LARP, and MCCC2 and negative for SPG11. The clinical features of the two affected sisters can be explained distinctively by each homozygous mutation in an oligogenic pattern of inheritance. This family represents an example of an oligogenic pattern of inheritance of mental retardation, short stature, spastic paraparesis, and osteopetrosis.

Keywords: mental retardation, short stature, spastic paraparesis, CA2, SPG11, LARP, oligogenic

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