scholarly journals Expansion and further delineation of the SETD5 phenotype leading to global developmental delay, variable dysmorphic features, and reduced penetrance

2018 ◽  
Vol 93 (4) ◽  
pp. 752-761 ◽  
Author(s):  
Z. Powis ◽  
K.D. Farwell Hagman ◽  
C. Mroske ◽  
K. McWalter ◽  
J.S. Cohen ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Global Developmental Delay ◽  
Dysmorphic Features ◽  
Reduced Penetrance

Molecular Delineation of Partial Trisomy 14q and Partial Trisomy 12p in a Patient with Dysmorphic Features, Heart Defect and Developmental Delay

2015 ◽  
Vol 145 (1) ◽  
pp. 14-18 ◽  
Author(s):  
Divya Bose ◽  
Venkatesh Krishnamurthy ◽  
K.S. Venkatesh ◽  
Mohamed Aiyaz ◽  
Mitesh Shetty ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Congenital Heart ◽  
Array Cgh ◽  
Partial Trisomy ◽  
Oligonucleotide Array ◽  
Global Developmental Delay ◽  
Potential Candidate ◽  
Balanced Translocation ◽  
Dysmorphic Features ◽  
Novel Association

This study describes a molecular analysis of partial trisomy 14q and partial trisomy 12p in a 5-year-old male child presenting with dysmorphic features, congenital heart disease and global developmental delay. Chromosomal analysis of the patient with GTG bands revealed a 47,XY,+der(14)t(12;14)(p13;q22)mat karyotype; the mother's karyotype was 46,XX,t(12;14)(p13;q22). Further, oligonucleotide array- CGH studies revealed an amplification of 32.3 Mb in the 14q11.1q22.1 region, substantiating partial trisomy 14q and additionally displaying an amplification of ∼1 Mb in the 12p13.3pter region for partial trisomy 12p. This is the first study to demonstrate a novel association of partial trisomies of 14q and 12p due to a 3:1 segregation of a maternal balanced translocation involving chromosomes 12 and 14. Gene ontology studies indicated 5 potential candidate genes in the amplified regions for the observed congenital anomalies.

Biallelic null variants in ZNF142 cause global developmental delay with familial epilepsy and dysmorphic features

2021 ◽  
Author(s):  
Shinichi Kameyama ◽  
Takeshi Mizuguchi ◽  
Hiromi Fukuda ◽  
Lip Hen Moey ◽  
Wee Teik Keng ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Global Developmental Delay ◽  
Dysmorphic Features

scholarly journals Adenosine Kinase Deficiency: Report and Review

2018 ◽  
Vol 50 (01) ◽  
pp. 046-050 ◽  
Author(s):  
Alhanouf Alhusani ◽  
Abdulrahman Obaid ◽  
Henk Blom ◽  
Anna Wedell ◽  
Majid Alfadhel
Keyword(s):  
Developmental Delay ◽  
Autosomal Recessive Disorder ◽  
Mendelian Inheritance ◽  
Developmental Dysplasia ◽  
Adenosine Kinase ◽  
Global Developmental Delay ◽  
Tall Stature ◽  
Current Case ◽  
Dysmorphic Features ◽  
The Central Nervous System

AbstractAdenosine kinase (ADK) deficiency (OMIM [online mendelian inheritance in man]: 614300) is an autosomal recessive disorder of adenosine and methionine metabolism, with a unique clinical phenotype, mainly involving the central nervous system and dysmorphic features. Patients usually present early in life with sepsis-like symptoms, respiratory difficulties, and neonatal jaundice. Subsequently, patients demonstrate hypotonia and global developmental delay. Biochemically, methionine is elevated with normal homocysteine levels and the diagnosis is confirmed through molecular analysis of the ADK gene. There is no curative treatment; however, a methionine-restricted diet has been tried with variable outcomes. Herein, we report a 4-year-old Saudi female with global developmental delay, hypotonia, and dysmorphic features. Interestingly, she has a tall stature, developmental dysplasia of the hip, optic nerve gliosis, and tigroid fundus. We found a mutation not reported previously and we compared the current case with previously reported cases. We alert clinicians to consider ADK deficiency in any neonate presenting with global developmental delay, hypotonia, dysmorphic features, and high methionine levels.

scholarly journals 22q13.32 Deletion and Duplication and Inversion in the Same Family: A Rare Occurrence

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Farooqua Jafri ◽  
James Fink ◽  
Rodney R. Higgins ◽  
Raymond Tervo
Keyword(s):  
Genetic Testing ◽  
Developmental Delay ◽  
Early Infancy ◽  
Deletion Syndrome ◽  
Global Developmental Delay ◽  
Rare Occurrence ◽  
Dysmorphic Features ◽  
Chromosome Imbalance ◽  
And Inversion ◽  
22Q13.3 Deletion Syndrome

Chromosome 22q13.3 deletion syndrome is a well-recognized cause of global developmental delay, while duplication of the same chromosome is a rare occurrence. The presence of both abnormalities in the same family has never been reported, to our knowledge. We report a rare occurrence of 22q13.3 duplication and 22q13.3 deletion in siblings, as a consequence of a mother's inversion on her 22nd chromosome (p13;q13.32). A 6 year old male was noted in infancy to have mild global developmental delay without dysmorphic features. His genetic testing revealed he had 22q13.3 duplication to the terminus. His 4 year old brother was noted in early infancy to have severe global developmental delay and dysmorphic features related to 22q13.3 deletion to the terminus. Their mother had a long inversion on her 22nd chromosome. Genetic tests for their father and eldest brother were unremarkable. The mother's inversion may rearrange to form 22q duplication or deletion when passed on to children. The chance of a child born with a chromosome imbalance is as high as 50%.

scholarly journals Bi-allelic CCDC47 Variants Cause a Disorder Characterized by Woolly Hair, Liver Dysfunction, Dysmorphic Features, and Global Developmental Delay

2018 ◽  
Vol 103 (5) ◽  
pp. 794-807 ◽  
Author(s):  
Marie Morimoto ◽  
Helen Waller-Evans ◽  
Zineb Ammous ◽  
Xiaofei Song ◽  
Kevin A. Strauss ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Liver Dysfunction ◽  
Global Developmental Delay ◽  
Dysmorphic Features ◽  
Woolly Hair

Exome reports A de novo GNB2 variant associated with global developmental delay, intellectual disability, and dysmorphic features

2020 ◽  
Vol 63 (4) ◽  
pp. 103804 ◽  
Author(s):  
Tokiko Fukuda ◽  
Takuya Hiraide ◽  
Kaori Yamoto ◽  
Mitsuko Nakashima ◽  
Tomoko Kawai ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
De Novo ◽  
Global Developmental Delay ◽  
Dysmorphic Features

scholarly journals Shukla-Vernon Syndrome: A Second Family with a Novel Variant in the BCORL1 Gene

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 452
Author(s):  
Babylakshmi Muthusamy ◽  
Anikha Bellad ◽  
Satish Chandra Girimaji ◽  
Akhilesh Pandey
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Protein Complexes ◽  
Neurodevelopmental Disorder ◽  
Missense Variant ◽  
Global Developmental Delay ◽  
Dysmorphic Features ◽  
Pathogenic Variants ◽  
Behavioral Abnormalities ◽  
Novel Variant

Shukla-Vernon syndrome (SHUVER) is an extremely rare neurodevelopmental disorder characterized by global developmental delay, intellectual disability, behavioral anomalies, and dysmorphic features. Pathogenic variants in the BCORL1 gene have been identified as the molecular cause for this disorder. The BCORL1 gene encodes for BCL-6 corepressor-like protein 1, a transcriptional corepressor that is an integral component of protein complexes involved in transcription repression. In this study, we report an Indian family with two male siblings with features of Shukla-Vernon syndrome. The patients exhibited global developmental delay, intellectual disability, kyphosis, seizures, and dysmorphic features including bushy prominent eyebrows with synophrys, sharp beaked prominent nose, protuberant lower jaw, squint, and hypoplastic ears with fused ear lobes. No behavioral abnormalities were observed. Whole exome sequencing revealed a novel potentially pathogenic arginine to cysteine substitution (p.Arg1265Cys) in the BCORL1 protein. This is the second report of Shukla-Vernon syndrome with a novel missense variant in the BCORL1 gene. Our study confirms and expands the phenotypes and genotypes described previously for this syndrome and should aid in diagnosis and genetic counselling of patients and their families.

scholarly journals A recurrent, homozygous EMC10 frameshift variant is associated with a syndrome of developmental delay with variable seizures and dysmorphic features

2021 ◽  
Author(s):  
Diane D. Shao ◽  
Rachel Straussberg ◽  
Hind Ahmed ◽  
Amjad Khan ◽  
Songhai Tian ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Global Developmental Delay ◽  
Endoplasmic Reticulum Membrane ◽  
Loss Of Function ◽  
Human Brain Tissue ◽  
Dysmorphic Features ◽  
Membrane Complex ◽  
Normal Human ◽  
Curly Hair ◽  
Neurodevelopmental Phenotype

Abstract Purpose The endoplasmic reticulum membrane complex (EMC) is a highly conserved, multifunctional 10-protein complex related to membrane protein biology. In seven families, we identified 13 individuals with highly overlapping phenotypes who harbor a single identical homozygous frameshift variant in EMC10. Methods Using exome, genome, and Sanger sequencing, a recurrent frameshift EMC10 variant was identified in affected individuals in an international cohort of consanguineous families. Multiple families were independently identified and connected via Matchmaker Exchange and internal databases. We assessed the effect of the frameshift variant on EMC10 RNA and protein expression and evaluated EMC10 expression in normal human brain tissue using immunohistochemistry. Results A homozygous variant EMC10 c.287delG (Refseq NM_206538.3, p.Gly96Alafs*9) segregated with affected individuals in each family, who exhibited a phenotypic spectrum of intellectual disability (ID) and global developmental delay (GDD), variable seizures and variable dysmorphic features (elongated face, curly hair, cubitus valgus, and arachnodactyly). The variant arose on two founder haplotypes and results in significantly reduced EMC10 RNA expression and an unstable truncated EMC10 protein. Conclusion We propose that a homozygous loss-of-function variant in EMC10 causes a novel syndromic neurodevelopmental phenotype. Remarkably, the recurrent variant is likely the result of a hypermutable site and arose on distinct founder haplotypes.

Paternal uniparental disomy of chromosome 19 in a pair of monochorionic diamniotic twins with dysmorphic features and developmental delay

2018 ◽  
Vol 55 (12) ◽  
pp. 847-852 ◽  
Author(s):  
Kit San Yeung ◽  
Matthew Sai Pong Ho ◽  
So Lun Lee ◽  
Anita Sik Yau Kan ◽  
Kelvin Yuen Kwong Chan ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Developmental Delay ◽  
Whole Exome Sequencing ◽  
Snp Array ◽  
Uniparental Disomy ◽  
Global Developmental Delay ◽  
Chromosome 19 ◽  
Dysmorphic Features ◽  
Whole Exome ◽  
Paternal Uniparental Disomy

BackgroundWe report here clinical, cytogenetic and molecular data for a pair of monochorionic diamniotic twins with paternal isodisomy for chromosome 19. Both twins presented with dysmorphic features and global developmental delay. This represents, to our knowledge, the first individual human case of paternal uniparental disomy for chromosome 19 (UPD19).MethodsWhole-exome sequencing, together with conventional karyotype and SNP array analysis were performed along with genome-wide DNA methylation array for delineation of the underlying molecular defects.ResultsConventional karyotyping on amniocytes and lymphocytes showed normal karyotypes for both twins. Whole-exome sequencing did not identify any pathogenic sequence variants but >5000 homozygous exonic variants on chromosome 19, suggestive of UPD19. SNP arrays on blood and buccal DNA both showed paternal isodisomy for chromosome 19. Losses of imprinting for known imprinted genes on chromosome 19 were identified, including ZNF331, PEG3, ZIM2 and MIMT1. In addition, imprinting defects were also identified in genes located on other chromosomes, including GPR1-AS, JAKMP1 and NHP2L1.ConclusionImprinting defects are the most likely cause for the dysmorphism and developmental delay in this first report of monozygotic twins with UPD19. However, epigenotype-phenotype correlation will require identification of additional individuals with UPD19 and further molecular analysis.

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