Mutation in the fukutin-related protein (FKRP) gene causes alpha-dystroglycanopathies, a group of autosomal recessive disorders associated with defective glycosylated alpha-dystroglycan (α-DG). The disease phenotype shows a broad spectrum, from the most severe congenital form involving brain and eye anomalies to milder limb-girdle form. FKRP-related alpha-dystroglycanopathies are common in European countries. However, a limited number of patients have been reported in Asian countries. Here, we presented the clinical, pathological, and genetic findings of nine patients with FKRP mutations identified at a single muscle repository center in Japan. Three and six patients were diagnosed with congenital muscular dystrophy type 1C and limb-girdle muscular dystrophy 2I, respectively. None of our Asian patients showed the most severe form of alpha-dystroglycanopathy. While all patients showed a reduction in glycosylated α-DG levels, to variable degrees, these levels did not correlate to clinical severity. Fifteen distinct pathogenic mutations were identified in our cohort, including five novel mutations. Unlike in the populations belonging to European countries, no common mutation was found in our cohort.

Congenital muscular dystrophy type 1C (MDC1C) is caused by the homozygous or compound heterozygous mutations of the FKRP gene. This article reported the clinical and mutation features of a child with MDC1C. The boy aged 8 months visited the hospital due to delayed development. As for clinical manifestations, the boy could not turn over or sit stably by himself, and there was a significant reduction in muscle tension; biceps reflex in both upper extremities and patellar tendon reflex and Achilles tendon reflex in both lower extremities could not be induced. The boy also had a stereotyped facial expression and strabismus. Gene detection revealed c.350C>G and c.1303C>T compound heterozygous mutations in the FKRP gene. The c.350C>G mutation came from the mother and had been reported as a pathogenic missense mutation. The c.1303C>T mutation came from the father and was a new missense mutation, and a bioinformatics analysis showed that it might be a pathogenic mutation. The boy was diagnosed with MDC1C with reference to the clinical features of hypotonia and motor developmental delay and FKRP gene mutation sequencing. 先天性肌营养不良1C型（MDClC）是由FKRP基因纯合或复合杂合突变引起。该文报道1例MDClC患儿的临床和基因突变特点。患儿，男，8月龄，因发育落后就诊。临床表现为翻身不佳、独坐不稳，肌张力低下，膝腱、跟腱反射不能引出，表情刻板，眼内斜视。基因检测证实患儿FKRP基因存在c.350C > G和c.1303C > T复合杂合突变；c.350C > G来自于母亲，为已报道的致病性错义突变；c.1303C > T来自于父亲，是新发错义突变，生物信息学软件分析预测其有致病可能。结合患儿早发肌张力低下、运动发育落后的临床特征和FKRP基因突变测序结果，确诊为MDC1C。

Mutations in the fukutin-related protein (FKRP) gene have been associated with dystroglycanopathies, which are common in Europe but rare in Asia. Our study aimed to retrospectively analyze and characterize the clinical, myopathological and genetic features of 12 Chinese patients with FKRP mutations. Three patients were diagnosed with congenital muscular dystrophy type 1C (MDC1C) and nine patients were diagnosed with limb girdle muscular dystrophy type 2I (LGMD2I). Three muscle biopsy specimens had dystrophic changes and reduced glycosylated α-dystroglycan staining, and two showed reduced expression of laminin α2. Two known and 13 novel mutations were identified in our single center cohort. Interestingly, the c.545A>G mutation was found in eight of the nine LGMD2I patients as a founder mutation and this founder mutation in Chinese patients differs from the one seen in European patients. Moreover, patients homozygous for the c.545A>G mutation were clinically asymptomatic, a less severe phenotype than in compound heterozygous patients with the c.545A>G mutation. The 13 novel mutations of FKRP significantly expanded the mutation spectrum of MDC1C and LGMD2I, and the different founder mutations indicate the ethnic difference in FKRP mutations.