HLD16
MCID: LKD029
MIFTS: 25

Leukodystrophy, Hypomyelinating, 16 (HLD16)

Categories: Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Muscle diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Leukodystrophy, Hypomyelinating, 16

MalaCards integrated aliases for Leukodystrophy, Hypomyelinating, 16:

Name: Leukodystrophy, Hypomyelinating, 16 57 73 28 5 38
Hld16 57 73

Characteristics:


Inheritance:

Autosomal dominant 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
variable severity
de novo mutation (in most patients)
onset in the first days or weeks of life
some patients may have normal cognitive development


Classifications:



Summaries for Leukodystrophy, Hypomyelinating, 16

OMIM®: 57 Hypomyelinating leukodystrophy-16 is an autosomal dominant neurologic disorder characterized by onset of hypotonia, nystagmus, and mildly delayed motor development in infancy. Affected individuals have motor disabilities, including ataxic or broad-based gait, hyperreflexia, intention tremor, dysmetria, and a mild pyramidal syndrome. Some patients have cognitive impairment, whereas others may have normal cognition or mild intellectual disability with speech difficulties. Brain imaging typically shows hypomyelination, leukodystrophy, and thin corpus callosum (summary by Simons et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see 312080. (617964) (Updated 08-Dec-2022)

MalaCards based summary: Leukodystrophy, Hypomyelinating, 16, is also known as hld16. An important gene associated with Leukodystrophy, Hypomyelinating, 16 is TMEM106B (Transmembrane Protein 106B). Affiliated tissues include brain, and related phenotypes are intellectual disability and seizure

UniProtKB/Swiss-Prot: 73 An autosomal dominant disorder characterized by hypomyelination, leukodystrophy, and thin corpus callosum observed on brain imaging. Clinical features include hypotonia, nystagmus, and mildly delayed motor development with onset in infancy, ataxic or broad-based gait, hyperreflexia, intention tremor, dysmetria, and a mild pyramidal syndrome. Some patients have cognitive impairment, whereas others may have normal cognition or mild intellectual disability with speech difficulties.

Symptoms & Phenotypes for Leukodystrophy, Hypomyelinating, 16

Human phenotypes related to Leukodystrophy, Hypomyelinating, 16:

30 (show all 30)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 30 Very rare (1%) HP:0001249
2 seizure 30 Very rare (1%) HP:0001250
3 failure to thrive 30 Very rare (1%) HP:0001508
4 abnormal pyramidal sign 30 Very rare (1%) HP:0007256
5 dysarthria 30 Very rare (1%) HP:0001260
6 hypotonia 30 Very rare (1%) HP:0001252
7 global developmental delay 30 Very rare (1%) HP:0001263
8 hypertonia 30 Very rare (1%) HP:0001276
9 absent speech 30 Very rare (1%) HP:0001344
10 dysmetria 30 Very rare (1%) HP:0001310
11 psychosis 30 Very rare (1%) HP:0000709
12 gait ataxia 30 Very rare (1%) HP:0002066
13 optic disc pallor 30 Very rare (1%) HP:0000543
14 feeding difficulties 30 Very rare (1%) HP:0011968
15 choreoathetosis 30 Very rare (1%) HP:0001266
16 hypoplasia of the corpus callosum 30 Very rare (1%) HP:0002079
17 intention tremor 30 Very rare (1%) HP:0002080
18 brisk reflexes 30 Very rare (1%) HP:0001348
19 shuffling gait 30 Very rare (1%) HP:0002362
20 vertical nystagmus 30 Very rare (1%) HP:0010544
21 delayed cns myelination 30 Very rare (1%) HP:0002188
22 saccadic smooth pursuit 30 Very rare (1%) HP:0001152
23 gaze-evoked nystagmus 30 Very rare (1%) HP:0000640
24 stooped posture 30 Very rare (1%) HP:0025403
25 horizontal pendular nystagmus 30 Very rare (1%) HP:0007811
26 rotary nystagmus 30 Very rare (1%) HP:0001583
27 delayed ability to walk 30 Very rare (1%) HP:0031936
28 dystonia 30 HP:0001332
29 broad-based gait 30 HP:0002136
30 leukodystrophy 30 HP:0002415

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Neurologic Central Nervous System:
hyperreflexia
dysarthria
dysmetria
dystonia
gait ataxia
more
Head And Neck Eyes:
saccadic pursuit
nystagmus (horizontal, vertical, rotary)

Muscle Soft Tissue:
hypotonia
hypertonia

Abdomen Gastrointestinal:
poor feeding (in some patients)

Clinical features from OMIM®:

617964 (Updated 08-Dec-2022)

Drugs & Therapeutics for Leukodystrophy, Hypomyelinating, 16

Search Clinical Trials, NIH Clinical Center for Leukodystrophy, Hypomyelinating, 16

Genetic Tests for Leukodystrophy, Hypomyelinating, 16

Genetic tests related to Leukodystrophy, Hypomyelinating, 16:

# Genetic test Affiliating Genes
1 Leukodystrophy, Hypomyelinating, 16 28 TMEM106B

Anatomical Context for Leukodystrophy, Hypomyelinating, 16

Organs/tissues related to Leukodystrophy, Hypomyelinating, 16:

MalaCards : Brain

Publications for Leukodystrophy, Hypomyelinating, 16

Articles related to Leukodystrophy, Hypomyelinating, 16:

# Title Authors PMID Year
1
The recurrent mutation in TMEM106B also causes hypomyelinating leukodystrophy in China and is a CpG hotspot. 57 5
29444210 2018
2
A recurrent de novo mutation in TMEM106B causes hypomyelinating leukodystrophy. 57 5
29186371 2017
3
A recurrent TMEM106B mutation in hypomyelinating leukodystrophy: A rapid diagnostic assay. 5
32595021 2020
4
A role of the frontotemporal lobar degeneration risk factor TMEM106B in myelination. 5
32572497 2020
5
TMEM106B and myelination: rare leukodystrophy families reveal unexpected connections. 5
29194508 2017
6
Identification of 14 novel GLB1 mutations, including five deletions, in 19 patients with GM1 gangliosidosis from South America. 5
17309651 2007
7
Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio B patients: possible common origin for the prevalent p.R59H mutation among gypsies. 5
16941474 2006
8
beta-galactosidase gene mutations affecting the lysosomal enzyme and the elastin-binding protein in GM1-gangliosidosis patients with cardiac involvement. 5
10737981 2000
9
Six novel beta-galactosidase gene mutations in Brazilian patients with GM1-gangliosidosis. 5
10338095 1999

Variations for Leukodystrophy, Hypomyelinating, 16

ClinVar genetic disease variations for Leukodystrophy, Hypomyelinating, 16:

5
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TMEM106B NM_001134232.2(TMEM106B):c.754G>A (p.Asp252Asn) SNV Pathogenic/Likely Pathogenic
523236 rs1554310600 GRCh37: 7:12271530-12271530
GRCh38: 7:12231904-12231904
2 TMEM106B NM_001134232.2(TMEM106B):c.55G>C (p.Asp19His) SNV Uncertain Significance
1028107 rs1781655491 GRCh37: 7:12254491-12254491
GRCh38: 7:12214865-12214865
3 TMEM106B NM_001134232.2(TMEM106B):c.442-44_442-43insGTTT INSERT Benign
1342220 GRCh37: 7:12269260-12269261
GRCh38: 7:12229634-12229635
4 TMEM106B NM_001134232.2(TMEM106B):c.686+29T>A SNV Benign
1342221 GRCh37: 7:12270770-12270770
GRCh38: 7:12231144-12231144
5 TMEM106B NM_001134232.2(TMEM106B):c.554C>G (p.Thr185Ser) SNV Benign
1168238 GRCh37: 7:12269417-12269417
GRCh38: 7:12229791-12229791
6 TMEM106B NM_001134232.2(TMEM106B):c.687-11A>G SNV Benign
1168270 GRCh37: 7:12271452-12271452
GRCh38: 7:12231826-12231826

UniProtKB/Swiss-Prot genetic disease variations for Leukodystrophy, Hypomyelinating, 16:

73
# Symbol AA change Variation ID SNP ID
1 TMEM106B p.Asp252Asn VAR_081068 rs1554310600

Expression for Leukodystrophy, Hypomyelinating, 16

Search GEO for disease gene expression data for Leukodystrophy, Hypomyelinating, 16.

Pathways for Leukodystrophy, Hypomyelinating, 16

GO Terms for Leukodystrophy, Hypomyelinating, 16

Sources for Leukodystrophy, Hypomyelinating, 16

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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