Exome sequencing identifies novel NTRK1 mutations in patients with HSAN-IV phenotype.
Hereditary sensory autonomic neuropathy type IV (HSAN-IV) is a rare autosomal recessive disorder that usually begins in infancy and is characterized by anhidrosis, insensitivity to noxious stimuli leading to self-mutilating behavior, and intellectual disability. HSAN-IV is caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene, NTRK1, encoding the high-affinity receptor of nerve growth factor (NGF) which maps to chromosome 1q21-q22. Patients with HSAN-IV lack all NGF-dependent neurons, the primary afferents and sympathetic postganglionic neurons leading to lack of pain sensation and the presence of anhidrosis, respectively. Herein, we report nine patients from nine unrelated families with HSAN-IV due to various mutations in NTRK1, five of which are novel. These are three missense and two nonsense mutations distributed in various domains of NTRK1 involved in binding of NGF. The affected patients had variable intellectual deficits, and some had delayed diagnosis of HSAN-IV. In addition to being the first report of HSAN-IV from the Arabian Peninsula, this report expands the mutational spectrum of patients with NTRK1 mutations and provides further insights for molecular and clinical diagnosis.
['Altassan|Ruqaiah|R|', 'Saud|Haya Al|HA|', 'Masoodi|Tariq Ahmad|TA|', 'Dosssari|Haya Al|HA|', 'Khalifa|Ola|O|', 'Al-Zaidan|Hamad|H|', 'Sakati|Nadia|N|', 'Rhabeeni|Zuhair|Z|', 'Al-Hassnan|Zuhair|Z|', 'Binamer|Yousef|Y|', 'Alhashemi|Nadia|N|', 'Wade|William|W|', 'Al-Zayed|Zayed|Z|', 'Al-Sayed|Moeen|M|', 'Al-Muhaizea|Mohamed A|MA|', 'Meyer|Brian|B|', 'Al-Owain|Mohammad|M|', 'Wakil|Salma M|SM|']
D000293:Adolescent D001483:Base Sequence D002648:Child D002675:Child, Preschool D002878:Chromosomes, Human, Pair 1 D018389:Codon, Nonsense D003241:Consanguinity D059472:Exome D005260:Female D015870:Gene Expression D005808:Genes, Recessive D009477:Hereditary Sensory and Autonomic Neuropathies D059014:High-Throughput Nucleotide Sequencing D006801:Humans D007007:Hypohidrosis D008607:Intellectual Disability D008297:Male D008958:Models, Molecular D020125:Mutation, Missense D020932:Nerve Growth Factor D009474:Neurons D010641:Phenotype D011485:Protein Binding D017433:Protein Structure, Secondary D020917:Receptor, trkA D012529:Saudi Arabia D016728:Self-Injurious Behavior D012720:Severity of Illness Index
ADHD-attention deficit hyperactivity disorder CIPA-congenital insensitivity to pain with anhidrosis HSAN-hereditary sensory and autonomic neuropathy NGF-nerve growth factor NTRK1-neurotrophic tyrosine kinase receptor type 1