Homozygosity mapping in 64 Syrian consanguineous families with non-specific intellectual disability reveals 11 novel loci and high heterogeneity

@article{Jamra2011HomozygosityMI,
  title={Homozygosity mapping in 64 Syrian consanguineous families with non-specific intellectual disability reveals 11 novel loci and high heterogeneity},
  author={Rami Abou Jamra and Sigrun Wohlfart and Markus Zweier and Steffen Uebe and Lutz Priebe and Arif B{\"u}lent Ekici and Susanne Giesebrecht and Ahmad Abboud and Mohammed Ayman Al Khateeb and Mahmoud Fakher and Saber Hamdan and Amina Ismael and Safia Muhammad and Markus M. N{\"o}then and Johannes Schumacher and Andr{\'e} Reis},
  journal={European Journal of Human Genetics},
  year={2011},
  volume={19},
  pages={1161-1166}
}
Non-specific intellectual disability of autosomal recessive inheritance (NS-ARID) represents an important fraction of severe cognitive dysfunction disorders. To date, only 10 genes have been identified, and further 24 linked-ARID loci have been reported, as well as others with suggestive linkage. To discover novel genes causing NS-ARID, we undertook genome-wide homozygosity mapping in 64 consanguineous multiplex families of Syrian descent. A total of 11 families revealed unique, significantly… 
View on Nature
nature.com
88 Citations
Highly Influential Citations
3
Background Citations
24
Methods Citations
6

88 Citations

Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families

The high yield of AR mutations for ID indicated that this approach has excellent clinical potential and should inform clinical diagnostics, including clinical whole exome and genome sequencing, for populations in which consanguinity is common.

Disruption of the methyltransferase-like 23 gene METTL23 causes mild autosomal recessive intellectual disability

3D-modelling of the protein indicates that METTL23 is strongly predicted to function as an S-adenosyl-methionine (SAM)-dependent methyltransferase, which supports the importance of methylation processes for intact neuronal function and brain development.

Molecular study of a consanguineous family with autosomal recessive mental retardation and speech disorder

The absence of any linkage of the Pakistani family with autosomal recessive MR to the eight well known loci, confirms the genetic heterogeneity of MR and helps in establishing the genotype-phenotype correlation of MR.

Hypomorphic Pathogenic Variants in TAF13 Are Associated with Autosomal-Recessive Intellectual Disability and Microcephaly.

Next Generation Sequencing and Genome-Wide Genotyping Identify the Genetic Causes of Intellectual Disability in Ten Consanguineous Families from Jordan.

  • T. Froukh
  • Biology
    The Tohoku journal of experimental medicine
  • 2017
Four genes and one CNV deletion/duplication are identified for the first time in association with ID in this pilot study, demonstrating the power of WES and homozygosity mapping for clinical diagnostics of ID in consanguineous families in small populations.

TRAPPC9-related autosomal recessive intellectual disability: report of a new mutation and clinical phenotype

It is found that homozygous TRAPPC9 loss-of-function mutations cause a distinctive phenotype, characterized by peculiar facial appearance, obesity, hypotonia (all signs resembling a Prader–Willi-like phenotype), moderate-to-severe ID, and consistent brain abnormalities.

SPATA5 mutations cause a distinct autosomal recessive phenotype of intellectual disability, hypotonia and hearing loss

It is independently confirmed that bi-allelic pathogenic variants in SPATA5 cause a syndromic form of intellectual disability, and its clinical presentation is delineated.

Whole exome sequencing is necessary to clarify ID/DD cases with de novo copy number variants of uncertain significance: Two proof‐of‐concept examples

The genetic definition of two sporadic cases, with syndromic ID/DD for whom array—Comparative Genomic Hybridization (aCGH) identified a de novo copy number variant (CNV) of uncertain significance, are reported, which document how interpreting de noovo array‐CGH variants represents a challenge in consanguineous families.

A Novel LINS1 Truncating Mutation in Autosomal Recessive Nonsyndromic Intellectual Disability

Clinical characteristics and genetic findings of a family with two male siblings affected with autosomal recessive nonsyndromic intellectual disability and Identification of a potentially pathogenic truncating mutation in LINS1 in two profoundly intellectually impaired patients also confirms its role in cognition.

Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature.

...

References

SHOWING 1-10 OF 31 REFERENCES

Autosomal recessive mental retardation: homozygosity mapping identifies 27 single linkage intervals, at least 14 novel loci and several mutation hotspots

Novel data indicate that common molecular causes of NS-ARMR do exist, and in the Iranian population, the most frequent ones may well account for several percent of the patients.

Five novel loci for inherited hearing loss mapped by SNP-based homozygosity profiles in Palestinian families

In communities with high rates of consanguinity and consequently high prevalence of recessive phenotypes, homozygosity mapping with SNP arrays is an effective approach for gene discovery. In 20…

Exome sequencing reveals a novel mutation for autosomal recessive non-syndromic mental retardation in the TECR gene on chromosome 19 p 13

The results reveal the value of massively parallel sequencing for identification of novel disease genes that could not be found using traditional approaches and identifies only the seventh causal mutation for autosomal recessive NSMR.

Exome sequencing reveals a novel mutation for autosomal recessive non-syndromic mental retardation in the TECR gene on chromosome 19p13.

The results reveal the value of massively parallel sequencing for identification of novel disease genes that could not be found using traditional approaches and identifies only the seventh causal mutation for autosomal recessive NSMR.

Identification of mutations in TRAPPC9, which encodes the NIK- and IKK-beta-binding protein, in nonsyndromic autosomal-recessive mental retardation.

A new locus for autosomal recessive non‐syndromic mental retardation maps to 1p21.1–p13.3

A large consanguineous Turkish family with four mentally retarded individuals from different branches of the family is presented, showing cognitive impairment but no neurological, skeletal, and biochemical involvements.

Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci

Homozygosity mapping in 78 consanguineous Iranian families with nonsyndromic autosomal recessive mental retardation has enabled us to determine the chromosomal localization of at least 8 novel gene loci for this condition.

Oligosaccharyltransferase-subunit mutations in nonsyndromic mental retardation.

High-resolution mapping of genotype-phenotype relationships in cri du chat syndrome using array comparative genomic hybridization.

High-resolution array comparative genomic hybridization was used to map DNA copy-number changes in 94 patients with cri du chat syndrome who had been carefully evaluated for the presence of the characteristic cry, speech delay, facial dysmorphology, and level of mental retardation, and results overlap and refine those reported in previous publications.

A defect in the TUSC3 gene is associated with autosomal recessive mental retardation.