scholarly journals Novel compound heterozygous mutations in WDR62 gene leading to developmental delay and Primary Microcephaly in Saudi Family

2019 ◽  
Vol 35 (3) ◽  
Author(s):  
Muhammad Imran Naseer ◽  
Mahmood Rasool ◽  
Angham Abdulrahman Abdulkareem ◽  
Adeel G. Chaudhary ◽  
Syed Kashif Zaidi ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Genetic Defect ◽  
Compound Heterozygous ◽  
Sequencing Analysis ◽  
The Novel ◽  
Primary Microcephaly ◽  
Saudi Family ◽  
Exon 9 ◽  
Compound Heterozygous Mutations

Objective: Primary microcephaly (MCPH) is a rare autosomal recessive disorder characterized by impaired congenital reduction of brain size along with head circumference and intellectual disability. MCPH is a heterogeneous disorder and more than twenty four genes associated with this disease have been identified so far. The objective of this study was to find out the novel genes or mutations leading to the genetic defect in a Saudi family with primary microcephaly. Methods: Whole exome sequencing was carried out to find the novel mutation and the results was further validated using Sanger sequencing analysis. This study was done in the Center of excellence in Genomic Medicine and Research, King Abdulaziz University under KACST project during 2017 and 2018. Results: We report a novel compound heterozygous mutations c.797C>T in exon 7 and c.1102G>A in exon 9 of the WD repeat domain 62 (WDR62) (OMIM 604317) gene in two affected siblings in Saudi family with intellectual disability, speech impediments walking difficulty along with primary microcephaly. Two rare, missense variants were detected in heterozygous state in the WDR62 gene in these two affected individuals from the heterozygous parents. Conclusions: A compound heterozygous mutations c.797C>T in exon 7 and c.1102G> A in exon 9 of the WDR62 gene was identified. WDR62 gene is very important gene and mutation can lead to neuro developmental defects, brain malformations, reduced brain and head size. These results should be taken into consideration during prognostic discussions and mutation spectrum with affected patients and their families in the Saudi population. doi: https://doi.org/10.12669/pjms.35.3.36 How to cite this:Naseer MI, Rasool M, Abdulkareem AA, Chaudhary AG, Zaidi SK, Al-Qahtani MH. Novel compound heterozygous mutations in WDR62 gene leading to developmental delay and Primary Microcephaly in Saudi Family. Pak J Med Sci. 2019;35(3):---------.  doi: https://doi.org/10.12669/pjms.35.3.36 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Novel compound heterozygous mutations in MCPH1 gene causes primary microcephaly in Saudi family

Neurosciences ◽  
2018 ◽  
Vol 23 (4) ◽  
pp. 347-350
Author(s):  
Muhammad Naseer ◽  
Mahmood Rasool ◽  
Angham Abdulkareem ◽  
Randa Bassiouni ◽  
Hussein Algahtani ◽  
...  
Keyword(s):  
Compound Heterozygous ◽  
Primary Microcephaly ◽  
Saudi Family ◽  
Compound Heterozygous Mutations

Primary Microcephaly With Anterior Predominant Pachygyria Caused by Novel Compound Heterozygous Mutations in ASPM

2015 ◽  
Vol 52 (5) ◽  
pp. e7-e8 ◽  
Author(s):  
Kazuyuki Nakamura ◽  
Takehiko Inui ◽  
Fuyuki Miya ◽  
Yonehiro Kanemura ◽  
Nobuhiko Okamoto ◽  
...  
Keyword(s):  
Compound Heterozygous ◽  
Primary Microcephaly ◽  
Compound Heterozygous Mutations

A novel mutation in PGAP2 gene causes developmental delay, intellectual disability, epilepsy and microcephaly in consanguineous Saudi family

2016 ◽  
Vol 371 ◽  
pp. 121-125 ◽  
Author(s):  
Muhammad Imran Naseer ◽  
Mahmood Rasool ◽  
Mohammed M. Jan ◽  
Adeel G. Chaudhary ◽  
Peter Natesan Pushparaj ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Novel Mutation ◽  
Saudi Family

scholarly journals Pitt Hopkins-Like Syndrome 1 with Novel CNTNAP2 Mutation in Siblings

2021 ◽  
Vol 8 ◽  
pp. 2329048X2110553
Author(s):  
Rea Mittal ◽  
Ashutosh Kumar ◽  
Roger Ladda ◽  
Gayatra Mainali ◽  
Ermal Aliu
Keyword(s):  
Developmental Delay ◽  
Focal Epilepsy ◽  
Autism Spectrum ◽  
Compound Heterozygous ◽  
Sequencing Analysis ◽  
Gait Abnormality ◽  
Pathogenic Variants ◽  
Obstructive Sleep ◽  
Management Guidance ◽  
Intragenic Deletions

Pitt Hopkins-like syndrome 1 (PTHLS1, OMIM # 610042) is an ultra-rare autosomal recessive condition with a prevalence of <1/1,000,000. Intragenic deletions of CNTNAP2 has been implicated in PTHLS1, however to our knowledge a compound heterozygous deletion of exon 4 and a c.1977_1989del13; p.V660Ffsx9 frameshift variant have not been published previously. In this case report, the proband is a seven year old female with PTHLS1, developmental delay, autism spectrum disorder, focal epilepsy, hypotonia, refractory errors, strabismus, and obstructive sleep apnea. Whole exome sequencing analysis revealed biallelic pathogenic variants of the CNTNAP2 gene. Proband has a three year old sister who has who has a similar phenotype including, developmental delay, epilepsy, gait abnormality, refractory errors, strabismus. Family variants were tested and she shared the same CNTNAP2 variants as her sister. The sisters described highlight two novel variants leading to PTHLS1. Genetic workup is essential in identification and management guidance in these populations.

scholarly journals Novel Compound Heterozygous Mutations in TTI2 Cause Syndromic Intellectual Disability in a Chinese Family

2019 ◽  
Vol 10 ◽  
Author(s):  
Rongrong Wang ◽  
Shirui Han ◽  
Hongyan Liu ◽  
Amjad Khan ◽  
Habulieti Xiaerbati ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Compound Heterozygous Mutations

scholarly journals A Novel ELP2 Compound Heterozygous Mutation in a Boy with Severe Intellectual Disability, Spastic Diplegia, Stereotypic Behavior and Review of the Current Literature

2020 ◽  
Vol 11 (5-6) ◽  
pp. 315-319
Author(s):  
Ayberk Turkyilmaz ◽  
Gunes Sager
Keyword(s):  
Intellectual Disability ◽  
Current Literature ◽  
Stereotypic Behavior ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Spastic Diplegia ◽  
Compound Heterozygous ◽  
Sequencing Analysis ◽  
Severe Intellectual Disability ◽  
Elongator Complex

The elongator complex consists of 6 highly conserved subunit proteins and is indispensable for various cellular functions, such as transcription elongation, histone acetylation, and tRNA modification. The elongator complex contains 2 subunits, each of which consists of 3 different proteins (encoded by the <i>ELP1–3</i> and <i>ELP4–6</i> genes). According to the OMIM database, <i>ELP2</i> gene variations have been reported to be associated with autosomal recessive mental retardation type 58. Here, we report a male patient with severe intellectual disability, spastic diplegia, and stereotypic behavior; in addition, we also provide a review of the current literature. Using whole-exome sequencing analysis, we detected a novel compound heterozygous variation in the <i>ELP2</i> gene. We present this case report to clarify the clinical findings of a very rare neurodevelopmental phenotype and to contribute new information to the current literature on genotype-phenotype correlations.

scholarly journals OTUD5 Variants Associated With X-Linked Intellectual Disability and Congenital Malformation

2021 ◽  
Vol 9 ◽  
Author(s):  
Ken Saida ◽  
Tokiko Fukuda ◽  
Daryl A. Scott ◽  
Toru Sengoku ◽  
Kazuhiro Ogata ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Ovarian Tumor ◽  
Brain Magnetic Resonance Imaging ◽  
Missense Variant ◽  
The Novel ◽  
Nasal Bridge ◽  
Congenital Cardiac Anomalies ◽  
Novel Variant ◽  
Long Term Prognosis

BackgroundX-linked intellectual disability (XLID), which occurs predominantly in males, is a relatively common and genetically heterogeneous disorder in which over 100 mutated genes have been reported. The OTUD5 gene at Xp11.23 encodes ovarian tumor deubiquitinase 5 protein, which is a deubiquitinating enzyme member of the ovarian tumor family. LINKage-specific-deubiquitylation-deficiency-induced embryonic defects (LINKED) syndrome, arising from pathogenic OTUD5 variants, was recently reported as a new XLID with additional congenital anomalies.MethodsWe investigated three affected males (49- and 47-year-old brothers [Individuals 1 and 2] and a 2-year-old boy [Individual 3]) from two families who showed developmental delay. Their common clinical features included developmental delay, hypotonia, short stature, and distinctive facial features, such as telecanthus and a depressed nasal bridge. Individuals 1 and 2 showed epilepsy and brain magnetic resonance imaging showed a thin corpus callosum and mild ventriculomegaly. Individual 3 showed congenital malformations, including tetralogy of Fallot, hypospadias, and bilateral cryptorchidism. To identify the genetic cause of these features, we performed whole-exome sequencing.ResultsA hemizygous OTUD5 missense variant, c.878A&gt;T, p.Asn293Ile [NM_017602.4], was identified in one family with Individuals 1 and 2, and another missense variant, c.1210 C&gt;T, p.Arg404Trp, in the other family with Individual 3, respectively. The former variant has not been registered in public databases and was predicted to be pathogenic by multiple in silico prediction tools. The latter variant p.Arg404Trp was previously reported as a pathogenic OTUD5 variant, and Individual 3 showed a typical LINKED syndrome phenotype. However, Individuals 1 and 2, with the novel variant (p.Asn293Ile), showed no cardiac or genitourinary malformations.ConclusionsUnlike previous reports of LINKED syndrome, which described early lethality with congenital cardiac anomalies, our three cases are still alive. Notably, the adult brothers with the novel missense OTUD5 variant have lived into their forties. This may be indicative of a milder phenotype as a possible genotype-phenotype correlation. These findings imply a possible long-term prognosis for individuals with this new XLID syndrome, and a wider phenotypic variation than initially thought.

scholarly journals Compound heterozygous mutations in the LTBP2 gene associated with microspherophakia in a Chinese patient: a case report and literature review

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Manhua Xu ◽  
Kaiming Li ◽  
Weimin He
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Chinese Patient ◽  
Western China ◽  
Compound Heterozygous ◽  
The Novel ◽  
Case Presentation ◽  
Ectopia Lentis ◽  
Compound Heterozygous Mutations ◽  
Next Generation Sequencing Ngs

Abstract Background Microspherophakia (MSP, OMIM 251,750) is a rare inherited autosomal recessive eye disorder characterized by small spherically shaped lens. Several studies have indicated that the transforming growth factor-beta (TGF-beta) binding proteins(LTBP2) gene mutation is the predominant cause of MSP. In our study, novel compound heterozygous mutations in the LTBP2 gene associated with MSP were reported, which was different from previous reported homozygous mutations. Case presentation The proband was an 18‐year‐old male in Western China with bilateral MSP, accompanied by ectopia lentis, secondary glaucoma and blindness in both eyes. In our hospital, he received bilateral lens resection and trabeculectomy combined with peripheral iridotomy. Using next-generation sequencing (NGS)-based gene panel tests, we identified pathogenic mutations in the peripheral blood DNA sample from the proband: c.3614_3618dupCTGGC (exon24, NM_000428) and c.2819G > A (exon18, NM_000428). The presence of the novel compound heterozygous mutations in the LTBP2 gene was linked with the development of MSP. Sanger sequencing confirmed the existence of one of the two variants in each parent respectively. Conclusion Our results demonstrated a rare case of MSP phenotype associated with novel compound heterozygous mutations in the LTBP2 gene using NGS technology.

scholarly journals The Novel Compound Heterozygous Mutations of GAA Gene in Mainland Chinese Patient with Classic Infantile-Onset Pompe Disease

2020 ◽  
Vol 61 (1) ◽  
pp. 178-182
Author(s):  
Jiaming Li ◽  
Yinghua Cui ◽  
Xin Wang ◽  
Qinglei Wang ◽  
Hongjun Wang ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Chinese Patient ◽  
Compound Heterozygous ◽  
The Novel ◽  
Mainland Chinese ◽  
Compound Heterozygous Mutations ◽  
Gaa Gene
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