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

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 st...

Full description

Saved in:
Bibliographic Details
Published in:Application of clinical genetics 2018-01, Vol.11, p.129-134
Main Authors: Alsemari, Abdulaziz, Alsuhaibani, Mohanned, Alhathlool, Rawabi, Ali, Bayan Mamdouh
Format: Article
Language:English
Subjects:
Bones
CA2
Calcification
Calcification (Physiology)
Deoxyribonucleic acid
Disease
DNA
DNA sequencing
Families & family life
Genes
Genetic aspects
Genetic research
Genomes
Genomics
Genotype & phenotype
Intellectual disabilities
LARP
Mental disorders
Mental retardation
Mutation
NMR
Novels
Nuclear magnetic resonance
oligogenic
Osteopetrosis
Paralysis
Short Report
Short stature
spastic paraparesis
SPG11
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1178-704X
1178-704X
DOI:10.2147/tacg.s172176