Browning Andrew C, Figueiredo Gustavo S, Baylis Oliver, Montgomery Emma, Beesley Clare, Molinari Elisa, Figueiredo Francisco C, Sayer John A
a Newcastle Eye Centre , Newcastle upon Tyne Hospitals NHS Foundation Trust , Newcastle upon Tyne , UK.
b Institute of Genetic Medicine, International Centre for Life, Newcastle University , Newcastle upon Tyne , UK.
Ophthalmic Genet. 2019 Apr;40(2):157-160. doi: 10.1080/13816810.2019.1592198. Epub 2019 Apr 6.
Ocular cystinosis is a rare autosomal recessive disorder caused by one severe and one mild mutation in the CTNS gene. It is characterised by cystine deposition within the cornea and conjunctiva however, the kidneys are not affected. We report a case of ocular cystinosis caused by two potentially severe CTNS mutations and discuss the possible mechanism of renal sparing.
This is an observational case report of the proband and her unaffected relatives. All subjects underwent ophthalmic examination, whilst in the proband, In vivo laser scanning confocal microscopy was used to demonstrate cystine crystals within her corneas and conjunctiva. Genetic diagnosis was confirmed by DNA sequencing of the proband and the segregation of the mutations was established in her relatives. RT-PCR of leukocyte RNA was undertaken to determine if aberrant splicing of the CTNS gene was taking place Results: The proband was found to have cystine crystals limited to the anterior corneal stroma and the conjunctiva. Sequencing of the proband's CTNS gene found her to be a compound heterozygote for a 27bp deletion in exon8/intron 8 (c.559_561 + 24del) and a novel c.635C>T variant in exon 9 that is predicted be pathogenic and to result in the substitution of alanine with valine at amino acid position 212 (p.Ala212Val), which is within the 3 transmembrane spanning domain of the CTNS protein. Examination of the proband's leukocyte RNA failed to demonstrate any aberrant CTNS gene splicing.
We present a case of ocular cystinosis caused by two potentially severe CTNS gene mutations. The lack of renal involvement may be due to localised (ocular) aberrant CTNS RNA splicing.
眼型胱氨酸病是一种罕见的常染色体隐性疾病，由CTNS基因的一个严重突变和一个轻度突变引起。其特征是角膜和结膜内有胱氨酸沉积，然而肾脏未受影响。我们报告一例由两个潜在严重的CTNS突变引起的眼型胱氨酸病病例，并讨论肾脏幸免的可能机制。
这是一份关于先证者及其未受影响亲属的观察性病例报告。所有受试者均接受了眼科检查，在先证者中，使用体内激光扫描共聚焦显微镜来显示其角膜和结膜内的胱氨酸晶体。通过对先证者进行DNA测序确诊基因诊断，并在其亲属中确定突变的分离情况。对白细胞RNA进行逆转录聚合酶链反应以确定CTNS基因是否发生异常剪接。结果：发现先证者的胱氨酸晶体仅限于角膜前基质和结膜。对先证者的CTNS基因进行测序发现，她是外显子8/内含子8中27bp缺失（c.559_561 + 24del）和外显子9中一个新的c.635C>T变异体的复合杂合子，该变异体预计具有致病性，并导致CTNS蛋白3个跨膜结构域内第212位氨基酸处的丙氨酸被缬氨酸取代（p.Ala212Val）。对先证者的白细胞RNA进行检查未发现任何CTNS基因异常剪接。
我们报告一例由两个潜在严重的CTNS基因突变引起的眼型胱氨酸病病例。肾脏未受累可能是由于局部（眼部）CTNS RNA异常剪接所致。
