Dataset Information

A Homozygous Missense Variant in INPP5E Associated with Joubert Syndrome and Related Disorders.

ABSTRACT: Joubert syndrome and related disorders (JSRD; ORPHA 140874) is a complex set of neurodevelopmental disorders with multiple organ involvement. JSRD is a type of ciliopathy which is caused by the presence of defective primary cilia in an individual. JSRD is commonly inherited in an autosomal recessive pattern, and more than 23 genes are known to be associated with JSRD. We report a novel homozygous mutation identified in the INPP5E gene, c.1303C>T, which leads to a change of an amino acid from arginine to tryptophan at residue 435 in the protein chain. In silico analysis indicates that p.Arg435Trp substitution affects the functionality of the protein product of the gene. Our result adds to the growing body of evidences that underlines the clinical utility of next-generation sequencing in the diagnosis of a genetic disorder when clinical features are inconclusive.

SUBMITTER: Shetty M

PROVIDER: S-EPMC5701266 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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A Homozygous Missense Variant in <i>INPP5E</i> Associated with Joubert Syndrome and Related Disorders.

Shetty Mitesh M Ramdas Nimmy N Sahni Shubhi S Mullapudi Nandita N Hegde Sridevi S

Molecular syndromology 20170908 6

Joubert syndrome and related disorders (JSRD; ORPHA 140874) is a complex set of neurodevelopmental disorders with multiple organ involvement. JSRD is a type of ciliopathy which is caused by the presence of defective primary cilia in an individual. JSRD is commonly inherited in an autosomal recessive pattern, and more than 23 genes are known to be associated with JSRD. We report a novel homozygous mutation identified in the <i>INPP5E</i> gene, c.1303C>T, which leads to a change of an amino acid f ...[more]

PMID: 29230161

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Project description:Joubert syndrome (JS) and related disorders (JSRD) are a group of developmental delay/multiple congenital anomalies syndromes in which the obligatory hallmark is the molar tooth sign (MTS), a complex midbrain-hindbrain malformation visible on brain imaging, first recognized in JS. Estimates of the incidence of JSRD range between 1/80,000 and 1/100,000 live births, although these figures may represent an underestimate. The neurological features of JSRD include hypotonia, ataxia, developmental delay, intellectual disability, abnormal eye movements, and neonatal breathing dysregulation. These may be associated with multiorgan involvement, mainly retinal dystrophy, nephronophthisis, hepatic fibrosis and polydactyly, with both inter- and intra-familial variability. JSRD are classified in six phenotypic subgroups: Pure JS; JS with ocular defect; JS with renal defect; JS with oculorenal defects; JS with hepatic defect; JS with orofaciodigital defects. With the exception of rare X-linked recessive cases, JSRD follow autosomal recessive inheritance and are genetically heterogeneous. Ten causative genes have been identified to date, all encoding for proteins of the primary cilium or the centrosome, making JSRD part of an expanding group of diseases called "ciliopathies". Mutational analysis of causative genes is available in few laboratories worldwide on a diagnostic or research basis. Differential diagnosis must consider in particular the other ciliopathies (such as nephronophthisis and Senior-Loken syndrome), distinct cerebellar and brainstem congenital defects and disorders with cerebro-oculo-renal manifestations. Recurrence risk is 25% in most families, although X-linked inheritance should also be considered. The identification of the molecular defect in couples at risk allows early prenatal genetic testing, whereas fetal brain neuroimaging may remain uninformative until the end of the second trimester of pregnancy. Detection of the MTS should be followed by a diagnostic protocol to assess multiorgan involvement. Optimal management requires a multidisciplinary approach, with particular attention to respiratory and feeding problems in neonates and infants. Cognitive and behavioral assessments are also recommended to provide young patients with adequate neuropsychological support and rehabilitation. After the first months of life, global prognosis varies considerably among JSRD subgroups, depending on the extent and severity of organ involvement.

Dataset Information

A Homozygous Missense Variant in INPP5E Associated with Joubert Syndrome and Related Disorders.

Publications

A Homozygous Missense Variant in <i>INPP5E</i> Associated with Joubert Syndrome and Related Disorders.

Similar Datasets

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