Clinical spectrum and gene mutations in a Chinese cohort with anoctaminopathy

Abstract

Recessive mutations in anoctamin-5 (ANO5) are causative for limb-girdle muscular dystrophy (LGMD) 2 L and non-dysferlin Miyoshi-like distal myopathy (MMD3). ANO5 mutations are highly prevalent in European countries; however it is not common in patients of Asian origin, and there is no data regarding the Chinese population. We retrospectively reviewed the clinical manifestations and gene mutations of Chinese patients with anoctaminopathy. A total of five ANO5 mutations including four novel mutations and one reported mutation were found in four patients from three families. No hotspot mutation was found. Three patients presented with presymptomatic hyperCKemia and one patient had limb muscle weakness. Muscle imaging of lower limbs showed preferential adductor magnus and medial gastrocnemius involvement. No hotspot mutation has been identified in Chinese patients to date.

Anoctamin 5 (ANO5) Muscle Disorders: A Narrative Review

“…In the United States, about 13% of LGMDR cases are LGMDR12 (7 % of LGMD) [ 16 ]. ANO5 muscular dystrophies are relatively uncommon in Asian and Middle Eastern populations, with only a few reported patients from these regions [ 17 , 18 , 19 , 20 , 21 , 22 ].…”

“…Homozygosity of the c.2272C > T mutation was found in 36% of Finnish patients [ 11 ]. None of these frequent pathogenic variants were found in reported Asian patients [ 17 , 18 , 19 , 22 ]. There is no established genotype–phenotype correlation in anoctaminopathy-5.…”

“…In a French cohort, LGMDR12 and MMD3 accounted for only 32% (12/38) and 16% (6/38), respectively, while over half of the patients expressed asymptomatic hyperCKemia or exercise intolerance phenotype [ 5 ]. From all the reported cases, the frequencies of LGMDR12, MMD3, pseudometabolic phenotype, and asymptomatic hyperCKemia are 66%, 11%, 11%, and 11%, respectively [ 2 , 3 , 4 , 5 , 6 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 25 , 26 , 27 , 29 , 37 , 41 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ].…”

ANO5-related muscle diseases: From clinics and genetics to pathology and research strategies

“…The ANO5 -gene consists of 22 exons and pathogenic variants seem to be evenly distributed throughout the gene. 8 , 9 , 11 , 14 , 25 , 29 , 33 Notably, some exons can harbor more than one pathogenic mutation and therefore might be more susceptible to DNA-changes. 14 Deletions and insertions within the ANO5 -gene were also reported 21 , 34 as well as missense mutations.…”

The Hereditary Progressive Limb-Girdle Muscular Dystrophy Type 2l (Anoctominopathy)

“…ПМКД 2L встречается в 2 раза чаще ПКМД 2В и занимает третье место по распространённости после ПКМД 2A и ПКМД 2I среди европейского населения, как и саркогликанопатии [7,8]. В азиатской популяции ПМКД 2L встречается очень редко, о чем свидетельствуют данные когортного исследования, проведенного в Китае [8]. В зарубежной литературе приводятся описания как единичных клинических случаев, так и групп пациентов с ПКМД 2L.…”