Whole-exome sequencing for monozygotic twins discordant for hemifacial microsomia

Aminoacyl transfer RNA (tRNA) synthetase complex-interacting multifunctional protein I is a noncatalytic component of tRNA multi-synthetase complexes. Although important in joining tRNAs to their cognate amino acids, AIMP1 has several other functions including axonal growth, cytokine activity, and interactions with N-acetylaspartic acid in ribosomal tRNA synthetase complexes. Further, N-acetylaspartic acid donates an aspartate during myelination and is therefore important to axonal integrity. Mutations in AIMP1 can disrupt these functions, as demonstrated in this clinical case study of 2 monozygotic twins, who display congenital opisthotonus, microcephaly, severe developmental delay, and seizures. Whole exome sequencing was used to identify a premature stop codon in the AIMP1 gene (g. 107248613_c.115C>T; p.(Gln39). In the absence of whole exome sequencing, we propose that decreased N-acetylaspartic acid peaks on magnetic resonance spectroscopy could act as a biomarker for AIMP1 mutations.

Download Full-text

Whole exome sequencing identifies compound heterozygous variants of CR2 gene in monozygotic twin patients with common variable immunodeficiency

SAGE Open Medicine ◽

10.1177/2050312120922652 ◽

2020 ◽

Vol 8 ◽

pp. 205031212092265

Author(s):

Adiratna Mat Ripen ◽

Hamidah Ghani ◽

Chai Teng Chear ◽

Mei Yee Chiow ◽

Sharifah Nurul Husna Syed Yahya ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Complex Disease ◽

Monozygotic Twins ◽

Compound Heterozygous ◽

Sequencing Analysis ◽

Missense Mutations ◽

Upper Respiratory Tract ◽

Whole Exome ◽

Tract Infections

Objectives: A pair of female Malay monozygotic twins who presented with recurrent upper respiratory tract infections, hepatosplenomegaly, bronchiectasis and bicytopenia were recruited in this study. Both patients were suspected with primary immunodeficiency diseases. However, the definite diagnosis was not clear due to complex disease phenotypes. The objective of this study was to identify the causative gene mutation in these patients. Methods: Lymphocyte subset enumeration test and whole exome sequencing were performed. Results: We identified a compound heterozygous CR2 mutation (c.1916G>A and c.2012G>A) in both patients. These variants were then confirmed using Sanger sequencing. Conclusion: Whole exome sequencing analysis of the monozygotic twins revealed compound heterozygous missense mutations in CR2.

Download Full-text

The black sheep of the family- whole-exome sequencing in family of lithium response discordant bipolar monozygotic twins

European Neuropsychopharmacology ◽

10.1016/j.euroneuro.2020.03.009 ◽

2020 ◽

Vol 34 ◽

pp. 19-27 ◽

Cited By ~ 1

Author(s):

Asaf Jacobs ◽

Michal Hagin ◽

Miraz Shugol ◽

Noam Shomron ◽

Nir Pillar ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Monozygotic Twins ◽

Black Sheep ◽

Whole Exome ◽

The Family ◽

Lithium Response

Download Full-text

Single Nucleotide Variants in A Family of Monozygotic Twins Discordant for the Phenotype Congenital Megaureter: A Genomic Analysis

The Open Urology & Nephrology Journal ◽

10.2174/1874303x01710010011 ◽

2017 ◽

Vol 10 (1) ◽

pp. 11-19

Author(s):

Augusto C. Soares dos Santos Junior ◽

Luciana B. Rodrigues ◽

Raony G. Corrêa Do Carmo Lisboa Cardenas ◽

Patricia G.P. Couto ◽

Luiz A. Cunha de Marco ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Monozygotic Twins ◽

Genomic Analysis ◽

Genetic Variations ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Whole Exome ◽

Sequencing Technique ◽

Related Individuals

Introduction: Congenital megaureter constitutes the second most frequent cause of hydronephrosis in children. There is still much debate on what extent environmental or genetic factors are involved in the pathogenesis of congenital megaureter. Objectives: This study aimed at investigating a pair of monozygotic twins discordant for the expression of bilateral congenital megaureter using the whole exome sequencing technique. Methods: Peripheral blood DNA was extracted and then sequenced using the whole exome technique from a pair of twins discordant for the presence of bilateral congenital refluxing unobstructed megaureter, his parents and a set of 11 non-related individuals with confirmed diagnosis of congenital megaureter. The DNA of the set of 11 non-related individuals was pooled in three groups. The monozygotic twins and their parents had DNA samples sequenced separately. Sanger validation was performed after data was filtered. Results: In the proband were identified 256 candidate genes, including TBX3, GATA6, DHH, LDB3, and HNF1, which are expressed in the urinary tract during the embryonic period. After Sanger validation, the SNVs found in the genes TBX3, GATA6, DHH and LDB3 were not confirmed in the proband. The SNV chr17:36104650 in the HNF1b gene was confirmed in the proband, his twin brother and the mother, however was not found in the pool of 11 non-related individuals with congenital megaureter. Conclusion: Due to the possible complex causative network of genetic variations and the challenges regarding the use of the whole exome sequencing technique we could not unequivocally associate the genetic variations identified in this study with the development of the congenital megaureter.

Download Full-text

Whole exome sequencing in monozygotic twins discordant for premature ovarian insufficiency

Fertility and Sterility ◽

10.1016/j.fertnstert.2015.07.342 ◽

2015 ◽

Vol 104 (3) ◽

pp. e111

Author(s):

N. Banks ◽

A. Martinez ◽

L. Brown ◽

J. Hughes ◽

A. DeCherney ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Monozygotic Twins ◽

Premature Ovarian Insufficiency ◽

Ovarian Insufficiency ◽

Whole Exome

Download Full-text

Whole-Exome Sequencing Reveals Rare Germline Mutations in Patients With Hemifacial Microsomia

Frontiers in Genetics ◽

10.3389/fgene.2021.580761 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiaojun Chen ◽

Fatao Liu ◽

Zin Mar Aung ◽

Yan Zhang ◽

Gang Chai

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Rare Variants ◽

Enrichment Analysis ◽

Germline Mutations ◽

Pathway Enrichment Analysis ◽

Hemifacial Microsomia ◽

Congenital Disease ◽

Pathway Enrichment ◽

Whole Exome

Hemifacial microsomia (HFM) is a rare congenital disease characterized by a spectrum of craniomaxillofacial malformations, including unilateral hypoplasia of the mandible and surrounding structures. Genetic predisposition for HFM is evident but the causative genes have not been fully understood. Thus, in the present study, we used whole-exome sequencing to screen 52 patients with HFM for rare germline mutations. We revealed 3,341 rare germline mutations in this patient cohort, including those in 13 genes previously shown to be associated with HFM. Among these HFM-related genes, NID2 was most frequently mutated (in 3/52 patients). PED4DIP, which has not been previously associated with HFM, exhibited rare variants most frequently (in 7/52 patients). Pathway enrichment analysis of genes that were mutated in >2 patients predicted the “laminin interactions” pathway to be most significantly disrupted, predominantly by mutations in ITGB4, NID2, or LAMA5. In summary, this study is the first to identify rare germline mutations in HFM. The likely disruptions in the signaling pathways due to the mutations reported here may be considered potential causes of HFM.

Download Full-text