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Case Reports
. 2021 Sep 3;21(1):384.
doi: 10.1186/s12887-021-02860-4.

Novel CLCN4 variant associated with syndromic X-linked intellectual disability in a Chinese girl: a case report

Xin Xu #  1 , Fen Lu #  1 , Li Zhang  2 , Hongying Li  1 , Senjie Du  1 , Jian Tang
Affiliations
Case Reports

Novel CLCN4 variant associated with syndromic X-linked intellectual disability in a Chinese girl: a case report

Xin Xu et al. BMC Pediatr. .

Abstract

Background: The Raynaud-Claes type of X-linked syndromic mental retardation (MRXSRC) is a very rare condition, by intellectual disability ranged from borderline to profound, impaired language development, brain abnormalities, facial dysmorphisms and seizures. MRXSRC is caused by variants in CLCN4 which encodes the 2Cl-/H+ exchanger ClC-4 prominently expressed in brain.

Case presentation: We present a 3-year-old Chinese girl with intellectual disability, dysmorphic features, brain abnormalities, significant language impairment and autistic features. Brain magnetic resonance imaging (MRI) showed a thin corpus callosum, a mega cisterna magna and ventriculomegaly. Whole exome sequencing (WES) was performed to detect the molecular basis of the disease. It was confirmed that this girl carried a novel heterozygous missense variant (c.1343C > T, p.Ala448Val) of CLCN4 gene, inherited from her mother. This variant has not been registered in public databases and was predicted to be pathogenic by multiple in silico prediction tools.

Conclusion: Our investigation expands the phenotype spectrum for CLCN4 variants with syndromic X-linked intellectual disability, which help to improve the understanding of CLCN4-related intellectual disability and will help in genetic counselling for this family.

Keywords: CLCN4 gene; Case report; Exome sequencing; Variants; X-linked syndromic mental retardation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Clinical and imaging features of the proband. a The picture illustrates the facial dysmorphic features consisting of bushy eyebrows, downslanted palpebral fissures, esotropia, depressed nasal bridge, and sparse teeth. b Brain MRI showed a thin corpus callosum, a mega cisterna magna and ventriculomegaly when the girl was 3 years old
Fig. 2
Fig. 2
Sequencing results and analysis. a The variation of c.1343C > T, p.Ala448Val is a missense variant identified in the proband and her mother. Her father did not carry the variant. Red arrows indicate the variant. b Orthologous protein sequence alignment of CLCN4 from different species. The mutated residue demonstrating conservation of alanine (Ala) at codon 448 is indicated by the arrow
Fig. 3
Fig. 3
Schematic diagrams showing structure of ClC-4. The variants were reported in HGMD and the literatures were shown in black, respectively. The position of the variant identified in this study are shown in red. CBS, cytosolic cystathionine-beta-synthase
See this image and copyright information in PMC

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