Duchenne Muscular Dystrophy in monozygotic twins; first follow up study worldwide

Abstract

Attached

D uchenne m uscular dystrophy (DMD), is a rare incidence in m onozygotic tw ins. W e report, to th e b est o f o u r know ledge/the first follow up study worldw ide on a genetically confirm ed sporadic case of monozygotic tw ins w ith DMD along w ith career detection in two generations. Socio-dem ographic characteristics a n d clinical data w ere recorded th rough a stan d ard questionnaire, and clinical assessm ent scales [Barthel Index (BI), H am m ersm ith m otor ability score, N orth S tar A m bulatory A ssessm ent (NSAA), y ig n o s an d Iro o k scales]. A follow-up w as perform ed after 15 m onths. M utation detection protocols included m ultiplex PCR (20 prim ers) followed by M ultiple Ligation d ep en d en t Probe Am plification (MLPA) using SALSA MLPA Kit P 0 3 4 /P 0 3 5 . Zygosity confirm ation w as perform ed w ith 13 STR m arkers. M ultiplex PCR revealed no deletion in th e h o tsp o t regions of th e dystrophin gene. MLPA analysis confirm ed dystrophin gene deletions in exons 6 1 ,6 2 w ith no duplications. C arrier statu s of th e m o th er an d th e sister of th e tw ins w ere confirm ed for exon 61,62. Clinical scores a t initial visit (Age 7yrs): Twin 1 [B I-55/100, H am m ersm ith -2 8 /4 0 , NSAA-8/34, Vignos scale-5/10, Brook scale-1/6] an d Twin 2 [B I-60/100, H am m ersm ith -2 8 /4 0 , NSAA-7/34, V ignos-5/10, B rook scale-1/6]. Clinical scores at follow up (Age 8yrs): Twin 1 [B I-10/100, H am m ersm ith -4 /4 0 , N SAA -0/34, Vignos scale-9/10, B rook scale-5/6] and Twin 2 [B I-10/100, H am m ersm ith-5/40, N SA A -0/34, V ignos-9/10, Brook scale-5/6]. The hig h er ra te o f disease progression w ith different m anifestations of th e disease in th e m onozygotic tw ins m ay be due to environm ental, genetic & epigenetic factors w hich shed a light on utilizing th is unique sam ple to identify new disease m odifying genes an d protein biom arkers.