Dataset Information

A novel missense variant in OTUD5 causes X-linked multiple congenital anomalies-neurodevelopmental syndrome.

ABSTRACT:

Background

The OTUD5 gene encodes a deubiquitinating enzyme (DUB) of the OTU family. Variants of OTUD5 are associated with X-linked multiple congenital anomalies-neurodevelopmental syndrome (MCAND). The case described in this study expands the clinical and molecular spectrum of OTUD5.

Methods

Trio-based clinical exome sequencing (trio-CES) was performed on a Chinese boy with a clinical phenotype and both of his parents. Sanger sequencing was employed for validation of the variant detected.

Results

The patient presented with characteristic facial features, intellectual disability, motor/language/cognitive, and global developmental delays, limb contractures, and kidney abnormalities, and trio-CES identified a de novo missense variant, c.1305T>A, of the OTUD5 gene.

Discussion

We describe OTUD5 gene variation in the Chinese population, with the first report of this variant. Additionally, we provide a comprehensive summary of all published cases of MCAND to date, in order to elucidate the primary clinical features of the syndrome and the variability in phenotype severity. This case expands the genetic and clinical phenotypic spectrum of OTUD5-associated MCAND.

SUBMITTER: Tian W

PROVIDER: S-EPMC10767676 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Publications

A novel missense variant in OTUD5 causes X-linked multiple congenital anomalies-neurodevelopmental syndrome.

Tian Weifang W Li Haiyu H Li Ying Y Guo Jing J Wang Handuo H Yang Bo B Li Pengyun P Cui Xueyin X Liu Ling L

Molecular genetics & genomic medicine 20231201 1

<h4>Background</h4>The OTUD5 gene encodes a deubiquitinating enzyme (DUB) of the OTU family. Variants of OTUD5 are associated with X-linked multiple congenital anomalies-neurodevelopmental syndrome (MCAND). The case described in this study expands the clinical and molecular spectrum of OTUD5.<h4>Methods</h4>Trio-based clinical exome sequencing (trio-CES) was performed on a Chinese boy with a clinical phenotype and both of his parents. Sanger sequencing was employed for validation of the variant ...[more]

PMID: 38037881

Similar Datasets

Project description: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>T, p.Asn293Ile [NM_017602.4], was identified in one family with Individuals 1 and 2, and another missense variant, c.1210 C>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.

Dataset Information

A novel missense variant in OTUD5 causes X-linked multiple congenital anomalies-neurodevelopmental syndrome.

Background

Methods

Results

Discussion

Publications

A novel missense variant in OTUD5 causes X-linked multiple congenital anomalies-neurodevelopmental syndrome.

Similar Datasets

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