Dubai: Sixteen new genetic mutations have been identified as causative of 12 rare hereditary diseases among Arab children in a recently concluded research project, Dr Mahmoud Taleb Al Ali, director of the Centre for Arab Genomic Studies (CAGS), revealed.
The centre, affiliated to the Shaikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences, conducted a joint research project with Latifa Hospital and found a link between 12 rare hereditary diseases among Arab children and 16 new genetic mutations in 14 genes.
The finding was included in 13 scientific research studies conducted on a group of 20 patients from the UAE, Jordan, Sudan and Yemen, and recently published in a number of international peer-reviewed PubMed-indexed journals.
In this context, Dr Al Ali commended the fruitful cooperation between the Shaikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences and the Dubai Health Authority and remarked: “The concerted efforts by clinical geneticists from Latifa Hospital and geneticists from CAGS made it possible and this finding will play a vital role in the completion of the Arab Genome.”
He also added: “This valuable scientific project boosts efforts exerted for the early detection of rare genetic diseases, and for finding out effective treatment for them. These serious disorders usually appear after birth, and can deteriorate quickly and may lead to death at an early age.”
Mutations and disorders
Dr Fatima Bastaki, consultant paediatrician and clinical geneticist at Latifa Hospital, said a genetic mutation has been discovered in the INSR gene which causes the Rapson-Mendenhall syndrome. Among the symptoms of this syndrome is early onset of diabetes in children, with very high resistance to insulin, along with skin deformities, short stature and muscle weakness.
The study also found a mutation in CDKN1C gene. “It leads to Beckwith-Weidmann syndrome, a disorder with asymmetrical overgrowth in the patients’ body organs and increased risk of cancer,” Dr Bastaki said.
“The study [also] discovered a new mutation in the SOX18 gene which leads to hypertrichosis-lymphedema-telangiectasia syndrome. Patients with this syndrome have spider veins, lose their hair, and suffer from oedema in their lower limbs.
“An additional cause of microcephaly was also uncovered, namely a novel mutation in the WDR62 gene. Patients with this syndrome have small head and brain, with mental disability.
“As for the novel mutation discovered in GPSM2 gene, it leads to Chudley-McCullough syndrome, which involves deafness, skull deformities, and accumulation of fluid inside the brain.
“Regarding the alpha-thalassaemia X–linked intellectual disability syndrome, it affects males more than females, and may occur as a result of a mutation in ATRX gene. Among the symptoms of this syndrome in children are severe developmental disability, speech delay, muscle weakness, birth defects and thalassaemia.”
Dr Abdul Razzaq Hemzeh, senior scientific coordinator, CAGS, said: “Novel genetic mutations have been discovered in both ECEL1 and CHRNG genes and these result in congenital arthrogryposis. Affected children suffer a number of musculoskeletal deformities such as contractures of knees and elbows.
“As for the previously unreported mutation in FGD1 gene, it leads to the Aarskog-Scott syndrome. Among the symptoms of this syndrome is mental retardation, congenital malformations of the face and muscular system, along with short stature.
“The study (also) revealed a link between Marinesco-Sjögren syndrome and a novel mutation in the SIL1 gene, which leads to muscles weakness, inability to control body movement, mental retardation, and cataracts.
“A novel mutation in the PNKP gene leads to dwarfism with microcephaly, and mental disability. As for the novel mutation discovered in ECHS1 gene, it leads to delayed mental and motor growth, muscle weakness, as well as heart disease.”
Dr Hemzeh added, “As for the autosomal recessive congenital ichthyosis cases, our studies showed the causality of four novel genetic mutations in TGM1, ABCA12, and ALOX12B genes. Among the symptoms of the disease are severe dryness and cracking of the patient’s skin, as well as many other skin disorders.”
The CAGS began working on this project in collaboration with Latifa Hospital in Dubai in March 2015. Over the next few months, more new genetic mutations and their relationship with many hereditary diseases in Arab children are expected to be revealed.