SSBP1基因突变致常染色体显性视神经萎缩症伴慢性肾功能不全1例并文献复习

SSBP1 mutation-induced autosomal dominant optic atrophy with chronic renal insufficiency:a case report and literature review

对2021年7月郑州大学附属儿童医院收治的1例SSBP1基因突变致常染色体显性视神经萎缩症(ADOA)伴慢性肾功能不全患儿的临床资料进行回顾性分析,并复习相关文献。患儿,女,10岁,因"发现生长迟缓3年,血肌酐升高2年"就诊。身高130 cm(低于健康同龄同性别第10百分位),体重22 kg(低于健康同龄同性别第3百分位)。尿素16.3 mmol/L,肌酐115.4μmol/L,估算肾小球滤过率41 mL/(min·1.73 m^(2)),伴代谢性酸中毒、轻度贫血;影像学示双肾体积小,实质回声增强,内可见散在点状高回声,皮髓质分界不清。患儿有视神经萎缩病史。患儿父亲、母亲无相关表型,患儿基因检测示c.320G>A(p.R107Q)杂合子错义突变,为自发突变。共检索到文献5篇,均为英文。SSBP1的基因突变共8种,含杂合子错义突变7种:c.320G>A(p.Arg107Gln)、c.119G>T(p.Gly40Val)、c.331G>C(p.Glu111Gln)、c.184A>G(p.Asn62Asp)、c.113G>A(p.Arg38Gln)、c.422G>A(p.Ser141Asn)、c.79G>A(p.Glu27Lys);纯合子突变1种:c.394A>G(p.Ile132Val)。携带SSBP1基因突变的患者几乎均有眼睛受累表现,部分伴肾功能进行性恶化、感音神经性耳聋、生长迟缓、甲状腺功能减退等表现。提示SSBP1基因突变可导致ADOA,对于以视神经萎缩起病的患儿,伴或不伴听力丧失及生长发育迟缓,建议积极行肾脏形态学及肾功能评估,及早行基因检查有助于诊治。

The data of a patient with autosomal dominant optic atrophy(ADOA)and chronic renal insufficiency caused by SSBP1 gene mutation in the Children′s Hospital Affiliated to Zhengzhou University in July 2021 was analyzed retrospectively.Literature was reviewed.The patient was a 10-year-old girl,who visited the hospital due to"growth retardation for the past 3 years and elevated serum creatinine(Scr)for the past 2 years".On admission,the patient′s height was 130 cm(<10th percentile of the same sex of healthy age)and her weight was 22 kg(<3rd precentile of the same sex of healthy age).Lab examination showed that the level of blood urea nitrogen(BUN)was 16.3 mmol/L,Scr was 115.4μmol/L,and the estimated glomerular filtration rate was 41 mL/(min·1.73 m^(2)).The patient was complicated with metabolic acidosis and mild anemia.Imaging findings showed small volume of both kidneys,increased background parenchymal enhancement,scattered spot-like hyperechoes and unclear boundary between the cortex and medulla.Additionally,the patient had a history of optic atrophy.Both the father and mother of the patient had no related phenotypes.The genetic test of the patient showed that c.320G>A(p.R107Q)was a heterozygous missense mutation,which was spontaneous.A total of 5 English papers were retrieved.There were 8 kinds of SSBP1 gene mutations reported,including 7 heterozygous missense mutations[c.320G>A(p.Arg107Gln),c.119G>T(p.Gly40Val),c.331G>C(p.Glu111Gln),c.184A>G(p.Asn62Asp),c.113G>A(p.Arg38Gln),c.422G>A(p.Ser141Asn),c.79G>A(p.Glu27Lys)]and 1 homozygous mutation[c.394A>G(p.Ile132Val)].Studies have established that almost all patients carrying SSBP1 mutations have manifestations of eye involvement,and that some patients are complicated with progressive deterioration of renal function,sensorineural deafness,growth retardation,and hypothyroidism.It suggests that SSBP1 gene mutation can cause ADOA.For patients with optic atrophy,whether they are complicated with hearing loss and growth retardation,renal morphology and renal function evaluation are recommended.Early genetic examination is helpful for diagnosis and treatment.