Autosomal recessive distal hereditary motor neuronopathy-7 (HMNR7) is characterized by onset of lower leg weakness in the first decade. Affected individuals have difficulty climbing stairs and problems standing on their heels... Most patients have foot deformities, and some may have leg muscle atrophy. The disorder is slowly progressive and often involves the upper limbs¹.

Prevalence

Biallelic variants found in 0.01% of 100 KGP participants; enriched in those with motor disease. 80% of VWA1 pathogenic variants are expansions/contractions². The repeat expansion was found in several ethnicities; founder mutation 7,000 years prior³.

Age of Onset

Typical: 1-3³; Range: 0-10¹.

HPO Terms

–

Association

Mendelian

Locus

hg19 chr1:1371178-1371198

hg38 chr1:1435798-1435818

t2t chr1:870158-870178

Details

Any deviation from 2 motifs is thought to be pathogenic².

Mechanism

LoF

Loss of function⁴.

Detection

Year

2021³

Location in Gene

Coding Exon 1

Gene Strand

Alleles

Ref. Motif

GGCGCGGAGC

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

GGCGCGGAGC

Pathogenic (gene)

AGCGGCGCGG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (gene)

–

gnomAD

References

Direct supporting references for info on this page.

1omim:619216

Resources for Genetics Professionals — Genetic Disorders Caused by Nucleotide Repeat Expansions and Contractions

Stephanie E.,Wallace, Lora JH,Bean

GeneReviews® [Internet] · 2022-10-20

genereviews:NBK535148

An ancestral 10-bp repeat expansion in VWA1 causes recessive hereditary motor neuropathy.

Alistair T,Pagnamenta, Rauan,Kaiyrzhanov, Yaqun,Zou, Sahar I,Da'as, Reza,Maroofian, Sandra,Donkervoort, Natalia,Dominik, Marlen,Lauffer, Matteo P,Ferla, Andrea,Orioli, Adam,Giess, Arianna,Tucci, Christian,Beetz, Maryam,Sedghi, Behnaz,Ansari, Rita,Barresi, Keivan,Basiri, Andrea,Cortese, Greg,Elgar, Miguel A,Fernandez-Garcia, Janice,Yip, A Reghan,Foley, Nicholas,Gutowski, Heinz,Jungbluth, Saskia,Lassche, Tim,Lavin, Carlo,Marcelis, Peter,Marks, Chiara,Marini-Bettolo, Livija,Medne, Ali-Reza,Moslemi, Anna,Sarkozy, Mary M,Reilly, Francesco,Muntoni, Francisca,Millan, Colleen C,Muraresku, Anna C,Need, Andrea H,Nemeth, Sarah B,Neuhaus, Fiona,Norwood, Marie,O'Donnell, Mary,O'Driscoll, Julia,Rankin, Sabrina W,Yum, Zarazuela,Zolkipli-Cunningham, Isabell,Brusius, Gilbert,Wunderlich, Mert,Karakaya, Brunhilde,Wirth, Khalid A,Fakhro, Homa,Tajsharghi, Carsten G,Bönnemann, Jenny C,Taylor, Henry,Houlden

Brain : a journal of neurology · 2021-03-03

pmid:33559681

Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications.

Indhu-Shree,Rajan-Babu, Egor,Dolzhenko, Michael A,Eberle, Jan M,Friedman

Nature reviews. Genetics · 2024-03-11

pmid:38467784