Hyperinsulinism

Gene: HK1

Green List (high evidence)

14 non-coding de novo variants affecting a 42-bp conserved region encompassed by a regulatory element in intron 2 of the hexokinase 1 gene (HK1) identified in individuals with hyperinsulinism.

Created: 9 Nov 2022, 9:43 a.m. | Last Modified: 9 Nov 2022, 9:44 a.m.

Panel Version: 1.0

Mono-allelic variants and ID: PMID30778173, 7 patients from 6 unrelated families with denovo missense variants in the N-terminal half of HK1

Mono-allelic variants and RP: Seven families reported with the same heterozygous missense variant, p.Glu847Lys and RP from different ethnicities. Some supportive evidence. Variant is present in 3 hets in gnomad.

Bi-allelic variants and haemolytic anaemia: more than 10 families reported.

Created: 3 May 2022, 10:31 p.m. | Last Modified: 3 May 2022, 10:31 p.m.

Panel Version: 0.13637

Bi-allelic variants and neuropathy: HMSNR is an autosomal recessive progressive complex peripheral neuropathy characterized by onset in the first decade of distal lower limb weakness and muscle atrophy resulting in walking difficulties. Distal impairment of the upper limbs usually occurs later, as does proximal lower limb weakness. There is distal sensory impairment, with pes cavus and areflexia. Laboratory studies suggest that it is a myelinopathy resulting in reduced nerve conduction velocities in the demyelinating range as well as a length-dependent axonopathy.

Founder variant in the Roma, -3818-195G-C, AltT2 EXON in 5'UTR identified in multiple families.

Note gene is associated with other phenotypes.

Created: 4 May 2021, 5:21 a.m. | Last Modified: 3 May 2022, 10:31 p.m.

Panel Version: 0.13637

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hyperinsulinism MONDO:0002177, HK1-related

Publications

• 36333503

Red List (low evidence)

Single family with hyperinsulinism.
Bi-allelic variants cause haemolytic anaemia, motor and sensory neuropathy.
Mono-allelic variants cause retinitis pigmentosa and neurodevelopmental syndrome.
Sources: Expert Review

Created: 14 Feb 2020, 3:30 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• 23859901