scholarly journals Wieacker‐Wolff syndrome, a distinctive phenotype of arthrogryposis multiplex congenita caused by a “de novo” ZC4H2 gene partial deletion

2021 ◽  
Vol 9 (9) ◽  
Author(s):  
Charlotte Deneufbourg ◽  
Armelle Duquenne ◽  
Jean‐Marc Biard ◽  
Yves Sznajer
Keyword(s):  
De Novo ◽  
Arthrogryposis Multiplex Congenita ◽  
Partial Deletion ◽  
Distinctive Phenotype

Intrafamilial Variability of the R694C Variant in BICD2 Presenting with Lethal Severe Arthrogryposis

2022 ◽  
pp. 097321792110688
Author(s):  
Francisco Ribeiro-Mourão ◽  
Ana Vilan ◽  
Sara Passos-Silva ◽  
Fernando Silveira ◽  
Miguel Leão ◽  
...  
Keyword(s):  
De Novo ◽  
Bone Fractures ◽  
Muscular Atrophy ◽  
Hip Dislocation ◽  
Arthrogryposis Multiplex Congenita ◽  
Pathogenic Variants ◽  
Genetic Abnormalities ◽  
Heterozygous Variant ◽  
Fetal Movements ◽  
Intrafamilial Variability

Arthrogryposis multiplex congenita (AMC) is a heterogeneous condition comprising congenital multiple joint contractures, and it is secondary to decreased fetal mobility following environmental/genetic abnormalities. BICD2 pathogenic variants have been associated with autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED2). We report the case of a newborn with decreased fetal movements and ventriculomegaly diagnosed in utero, born with severe AMC, multiple bone fractures, congenital hip dislocation, and respiratory insufficiency that led to neonatal death. His mother had AMC diagnosis without established etiology. Her phenotype characterization was key to guide the genetic investigation. A BICD 2 heterozygous variant (NM_001003800.1; c.2080C > T; p. [Arg694Cys]) was detected both in the mother and the newborn. This variant had previously been reported in 3 cases, all having de novo severe SMALED-type 2B (MIM#618291) phenotype. This is the first report of this variant (p. [Arg694Cys]) presenting with an inherited, severe, and lethal phenotype associated to intrafamilial variability, suggesting a more complex phenotype-genotype correlation than previously stated.

A de novo 1q23.3-q24.2 deletion combined with a GORAB missense mutation causes a distinctive phenotype with cutis laxa

2016 ◽  
Vol 62 (2) ◽  
pp. 325-328 ◽  
Author(s):  
Mohammed Al-Bughaili ◽  
Teresa M Neuhann ◽  
Ricarda Flöttmann ◽  
Stefan Mundlos ◽  
Malte Spielmann ◽  
...  
Keyword(s):  
Missense Mutation ◽  
De Novo ◽  
Cutis Laxa ◽  
Distinctive Phenotype

Cleft Lip Palate in a Patient with 5q14.3 Deletion Syndrome: A Possible Unreported Feature?

2022 ◽  
pp. 1-8
Author(s):  
Liliana Fernández Hernández ◽  
Miguel A. Alcántara Ortigoza ◽  
Sandra E. Ramos Angeles ◽  
Ariadna González-del Angel
Keyword(s):  
Intellectual Disability ◽  
Sanger Sequencing ◽  
Cleft Lip ◽  
De Novo ◽  
Deletion Syndrome ◽  
Facial Dysmorphism ◽  
Brain Malformations ◽  
Bilateral Cleft Lip ◽  
Cleft Lip Palate ◽  
Distinctive Phenotype

5q14.3 deletion syndrome (MIM#613443) is an uncommon but well-known syndrome characterized by intellectual disability, epilepsy, hypotonia, brain malformations, and facial dysmorphism. Most patients with this syndrome have lost one copy of the <i>MEF2C</i> gene (MIM*600662), whose haploinsufficiency is considered to be responsible for the distinctive phenotype. To date, nearly 40 cases have been reported; the deletion size and clinical spectrum are variable, and at least 6 cases without <i>MEF2C</i> involvement have been documented. We herein report the clinical and cytogenomic findings of an 11-year-old girl who has a 5q14.3q21.1 de novo deletion that does not involve <i>MEF2C</i> but shares the clinical features described in other reported patients. Moreover, she additionally presents with bilateral cleft-lip palate (CLP), which has not been previously reported as a feature of the syndrome. The most frequent syndromic forms of CLP were ruled out in our patient mainly by clinical examination, and Sanger sequencing was performed to discard the presence of a <i>TBX22</i> gene (MIM*300307) defect. Our report suggests CLP as a possible unreported feature and redefines the critical phenotypic regions of 5q14.3 deletion syndrome.

De novo pathogenic variant in TUBB2A presenting with arthrogryposis multiplex congenita, brain abnormalities, and severe developmental delay

2017 ◽  
Vol 173 (10) ◽  
pp. 2725-2730 ◽  
Author(s):  
Resham Ejaz ◽  
Anath C. Lionel ◽  
Susan Blaser ◽  
Susan Walker ◽  
Stephen W. Scherer ◽  
...  
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Pathogenic Variant ◽  
Arthrogryposis Multiplex Congenita ◽  
Brain Abnormalities

A patient with de-novo partial deletion of Xp (p11.4–pter) and partial duplication of 22q (q11.2–qter)

2008 ◽  
Vol 17 (1) ◽  
pp. 23-26
Author(s):  
Christine M. Armour ◽  
Jean McGowan-Jordan ◽  
Sarah E. Lawrence ◽  
Amélie Bouchard ◽  
Mark Basik ◽  
...  
Keyword(s):  
De Novo ◽  
Partial Deletion ◽  
Partial Duplication

scholarly journals Male Infertility Caused by a de Novo Partial Deletion of the DAZ Cluster on the Y Chromosome1

2000 ◽  
Vol 85 (11) ◽  
pp. 4069-4073
Author(s):  
Enrico Moro ◽  
Alberto Ferlin ◽  
Pauline Hsiao Yen ◽  
Paolo Guanciali Franchi ◽  
Giandomenico Palka ◽  
...  
Keyword(s):  
Male Infertility ◽  
De Novo ◽  
Point Mutations ◽  
De Novo Mutation ◽  
Specific Gene ◽  
Partial Deletion ◽  
Severe Oligozoospermia ◽  
First Case ◽  
Factor C ◽  
Spermatogenic Failure

Deletions in distal Yq interval 6 represent the cause of 10–15% of idiopathic severe male infertility and map to a region defined AZFc (azoospermia factor c). The testis-specific gene DAZ is considered a major AZFc candidate, and its deletion has been associated with a severe disruption in spermatogenesis. However, DAZ is actually a multicopy gene family consisting of seven clustered copies spanning about 1 megabase. Only deletions removing the entire DAZ gene cluster together with other genes have been reported in infertile males. Because no case of spermatogenic failure has been traced to intragenic deletions, point mutations, or even deletions not involving all the DAZ copies, the definitive proof for a requirement of DAZ for spermatogenesis is still debatable. Here we report the first case of a partial deletion of the DAZ cluster removing all but one of the copies. This deletion is present in a patient affected with severe oligozoospermia who had a testicular phenotype characterized by a great quantitative reduction of germ cells (severe hypospermatogenesis). The absence of this deletion in the fertile brother of the patient suggests that this de novo mutation indeed caused the spermatogenic failure.

scholarly journals Phenotypic spectrum and genomics of undiagnosed arthrogryposis multiplex congenita

2021 ◽  
pp. jmedgenet-2020-107595
Author(s):  
Annie Laquerriere ◽  
Dana Jaber ◽  
Emanuela Abiusi ◽  
Jérome Maluenda ◽  
Dan Mejlachowicz ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
De Novo ◽  
Genetic Diagnosis ◽  
Added Value ◽  
Disease Genes ◽  
Arthrogryposis Multiplex Congenita ◽  
Pathogenic Variants ◽  
New Genes ◽  
Whole Exome ◽  
Disease Loci

BackgroundArthrogryposis multiplex congenita (AMC) is characterised by congenital joint contractures in two or more body areas. AMC exhibits wide phenotypic and genetic heterogeneity. Our goals were to improve the genetic diagnosis rates of AMC, to evaluate the added value of whole exome sequencing (WES) compared with targeted exome sequencing (TES) and to identify new genes in 315 unrelated undiagnosed AMC families.MethodsSeveral genomic approaches were used including genetic mapping of disease loci in multiplex or consanguineous families, TES then WES. Sanger sequencing was performed to identify or validate variants.ResultsWe achieved disease gene identification in 52.7% of AMC index patients including nine recently identified genes (CNTNAP1, MAGEL2, ADGRG6, ADCY6, GLDN, LGI4, LMOD3, UNC50 and SCN1A). Moreover, we identified pathogenic variants in ASXL3 and STAC3 expanding the phenotypes associated with these genes. The most frequent cause of AMC was a primary involvement of skeletal muscle (40%) followed by brain (22%). The most frequent mode of inheritance is autosomal recessive (66.3% of patients). In sporadic patients born to non-consanguineous parents (n=60), de novo dominant autosomal or X linked variants were observed in 30 of them (50%).ConclusionNew genes recently identified in AMC represent 21% of causing genes in our cohort. A high proportion of de novo variants were observed indicating that this mechanism plays a prominent part in this developmental disease. Our data showed the added value of WES when compared with TES due to the larger clinical spectrum of some disease genes than initially described and the identification of novel genes.

Recurrent de novo BICD2 mutation associated with arthrogryposis multiplex congenita and bilateral perisylvian polymicrogyria

2016 ◽  
Vol 26 (11) ◽  
pp. 744-748 ◽  
Author(s):  
Gianina Ravenscroft ◽  
Nataliya Di Donato ◽  
Gabriele Hahn ◽  
Mark R. Davis ◽  
Paul D. Craven ◽  
...  
Keyword(s):  
De Novo ◽  
Arthrogryposis Multiplex Congenita

scholarly journals Deleterious de novo variants of X‐linked ZC4H2 in females cause a variable phenotype with neurogenic arthrogryposis multiplex congenita

2019 ◽  
Vol 40 (12) ◽  
pp. 2270-2285 ◽  
Author(s):  
Suzanna G.M. Frints ◽  
Friederike Hennig ◽  
Roberto Colombo ◽  
Sebastien Jacquemont ◽  
Paulien Terhal ◽  
...  
Keyword(s):  
De Novo ◽  
Arthrogryposis Multiplex Congenita ◽  
Variable Phenotype
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