Original articleNovel mutation in SLC9A6 gene in a patient with Christianson syndrome and retinitis pigmentosum
Introduction
Christianson syndrome (CS, MIM#300243) is an X-linked mental retardation syndrome affecting males with profound mental retardation (MR), epilepsy, ophthalmoplegia, microcephaly, and ataxia with cerebellar atrophy [1]. Carrier females may have learning difficulties [2]. Mutations in the SLC9A6 gene were recently identified in six families with multiple male cases and in two sporadic male patients [2], [3], [4], [5]. A recent study suggested that disease-causing mutations induce a loss of function of the gene product, the Na+/H+ exchanger protein member 6 (NHE6) [5]. NHE6 is ubiquitously expressed in the membrane of early recycling endosomes, which is essential for the growth of neuronal dendritic spines. As a consequence, mutations in SLC9A6 may impair the neuronal development [5].
Herein, we report on a further patient with CS, who displayed obvious progressive cerebellar atrophy, retinitis pigmentosum and a novel mutation in SLC9A6.
Section snippets
Patient description
This patient, now aged 22 years, was the second child born to non-consanguineous healthy parents (Fig. 1A). His older sister, as well as his mother, had no history of learning difficulties. Pregnancy and delivery were uneventful, and growth parameters at birth were normal, including an occipitofrontal circumference (OFC) of 33 cm.
Initial steps of his motor development did not raise any concern: the patient held his head at three months, sat alone at 8.5 months and walked independently at 18 months.
Mutation analysis
A blood sample from the patient was collected after having obtained written informed consent. Genomic DNA was extracted from peripheral blood lymphocytes using the Flexigene DNA kit (Qiagen, Courtaboeuf, France). The 16 SLC9A6 coding exons and intron–exon junctions were PCR-amplified using 12 primers pairs (sequences available on request). PCR products were then sequenced with Big Dye Terminator cycle sequencing kit and ABI 3730xl automated sequencer (PE Applied Biosystems).
Sequencing revealed
Discussion
Thirty-eight patients with CS, belonging to eight families, are reported to date, and the phenotype has been delineated from the description of 24 examined patients (Table 1). All patients were affected by profound MR except one with moderate MR [2]. We report a new patient affected with CS carrying a novel SLC9A6 mutation.
Behavioral abnormalities suggesting pervasive developmental disorder were the prominent clinical feature in our patient during the first 2 years of life. At that time, he
Ethical standards/Conflict of interest
The authors confirm that the present submitted work complies with the current laws of the country in which it was performed (France).
The authors declare that they have no conflict of interest.
Acknowledgement
The authors thank Dr. Gregor Gilfillan for providing the sequence of primers for SLC9A6 sequencing.
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