Hereditary motor and sensory neuropathy-type Lom (HMSNL), also known as CMT4D, a demyelinating neuropathy with late-onset deafness is an autosomal recessive disorder threatening Roma population worldwide. The clinical phenotype was reported in several case reports before the gene discovery. HMSNL is caused by a homozygous founder mutation p.Arg148* in the N-Myc downstream-regulated gene 1. Here, we report findings from the Czech Republic, where HMSNL was found in 12 Czech patients from eight families. In these 12 patients, 11 of the causes were due to p.Arg148* mutation inherited from both parents by the autosomal recessive mechanism. But in one case, the recessive mutation was inherited only from one parent (father) and unmasked owing to an uniparental isodisomy of the entire chromosome eight. The inherited peripheral neuropathy owing to an isodisomy of the whole chromosome pointed to an interesting, less frequent possibility of recessive disease and complications with genetic counseling.

Centre for Medical Genetics and Reproductive Medicine GENNET Prague Czech Republic

Department of Neurology 2nd Faculty of Medicine Charles University Prague and Motol University Hospital Prague Czech Republic

Department of Paediatric Neurology DNA Laboratory 2nd Faculty of Medicine Charles University Prague and Motol University Hospital Prague Czech Republic

Pediatric Neurology Matice školské 17 České Budejovice Czech Republic

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Am J Hum Genet. 2000 Jul;67(1):47-58 PubMed

Neuromuscul Disord. 1998 May;8(3-4):182-5 PubMed

Clin Genet. 2015 Apr;87(4):395-7 PubMed

J Peripher Nerv Syst. 2013 Sep;18(3):261-5 PubMed

J Appl Genet. 2013 Nov;54(4):455-60 PubMed

Orphanet J Rare Dis. 2016 Aug 22;11(1):118 PubMed

Nat Genet. 1996 Oct;14(2):214-7 PubMed

Clin Genet. 2016 Aug;90(2):161-5 PubMed

Genet Med. 2014 May;16(5):386-94 PubMed

Neuromuscul Disord. 2007 Feb;17(2):163-8 PubMed

Neurology. 2008 Mar 18;70(12):976-8 PubMed

Neuromuscul Disord. 2000 Dec;10(8):578-83 PubMed

Neuromuscul Disord. 1998 Apr;8(2):90-4 PubMed

Hum Mutat. 2003 Aug;22(2):129-35 PubMed

J Peripher Nerv Syst. 2011 Mar;16(1):1-14 PubMed

Pflugers Arch. 2000;439(3 Suppl):R208-10 PubMed

Neurogenetics. 2009 Apr;10(2):105-10 PubMed

Am J Med Genet A. 2005 Jul 30;136(3):287-305 PubMed

Acta Myol. 2008 Oct;27:59-62 PubMed

Ann Neurol. 1999 Jul;46(1):36-44 PubMed

Eur J Hum Genet. 2006 Nov;14(11):1158-69 PubMed

Brain. 1998 Mar;121 ( Pt 3):399-408 PubMed

Am J Med Genet C Semin Med Genet. 2010 Aug 15;154C(3):329-34 PubMed

Neuromuscul Disord. 2000 Dec;10(8):584-91 PubMed

Clin Genet. 2013 Jun;83(6):565-70 PubMed

Clin Genet. 2011 Oct;80(4):334-45 PubMed

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