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The first case of deafness-dystonia syndrome due to compound heterozygous variants in FITM2.

ABSTRACT: We report the second known family affected by deafness-dystonia syndrome associated with loss of function of FITM2. Our patient is compound heterozygous for pathogenic FITM2 variants, while affected siblings in the first report were homozygous. This case provides evidence that this novel genetic disorder is associated with autosomal recessive inheritance.

SUBMITTER: Shakir A

PROVIDER: S-EPMC6132111 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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The first case of deafness-dystonia syndrome due to compound heterozygous variants in FITM2.

Shakir Aamina A Wadley Alexandrea F AF Purcarin Gabriela G Wierenga Klaas J KJ

Clinical case reports 20180726 9

We report the second known family affected by deafness-dystonia syndrome associated with loss of function of FITM2. Our patient is compound heterozygous for pathogenic FITM2 variants, while affected siblings in the first report were homozygous. This case provides evidence that this novel genetic disorder is associated with autosomal recessive inheritance. ...[more]

PMID: 30214770

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Project description:BACKGROUND:Joubert syndrome is a genetically heterogeneous autosomal recessive ciliopathy characterized by the combination of hypoplasia/aplasia of the cerebellar vermis, thickened and elongated superior cerebellar peduncles and a deep interpeduncular fossa, known as "molar tooth sign" associated with hypotonia, respiratory control disturbances and abnormal eye movements. To date, pathogenic variants in over 35 genes are known to cause autosomal recessive Joubert Syndrome, while one gene is associated with X-linked recessive inheritance. CASE PRESENTATION:We describe here a non-consanguineous Vietnamese family with Joubert syndrome, a fetus and 10-year-old developmentally delayed boy. Ultrasonography showed ventriculomegaly at 26 + 6 weeks of gestation in the fetus. The 10-year-old-boy was diagnosed with cerebral palsy of unknown origin. Clinical physical examination at the age of 10, he showed clinical features of Joubert syndrome including typical facial dysmorphism, ataxia, severe psychomotor delay, oculomotor apraxia and molar tooth sign on brain MRI. Whole exome sequencing analysis identified a novel compound heterozygous c.725A > G p.Asn242Ser and c.313-3 T > G p.Lys105Valfs*16 TMEM67 variant in the proband and the affected fetus. These two variants were inherited from each parent and confirmed by Sanger sequencing. The variant c.725A > G p.Asn242Ser was previously documented in patients with JS, the novel splice-site c.313-3 T > G p.Lys105Valfs*16 TMEM67 variant produced an aberrant transcript with the loss of four nucleotides of exon 03. CONCLUSION:This study confirms the diagnosis of Joubert syndrome in a Vietnamese family and expands the mutational spectrum of TMEM67 sequence variations. We also highlight the importance of molecular approaches to unravel underlying mechanisms of human genetic disorders. Early precise diagnosis could help provide further accurate genetic counseling for recurrence-risk assessment, future diagnostic option, management as well as treatment guidance for rare disorders.

Dataset Information

The first case of deafness-dystonia syndrome due to compound heterozygous variants in FITM2.

Publications

The first case of deafness-dystonia syndrome due to compound heterozygous variants in <i>FITM2</i>.

Similar Datasets

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