Hao-Yi Tan1, Bin Wang2, Yuan-Zong Song3. 1. Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangdong, 510630, China. 2. Department of Pediatrics, Zhujiang Hospital, Southern Medical University, Guangdong, 510280, China. 3. Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangdong, 510630, China. songyuanzong@vip.tom.com.
Abstract
BACKGROUND: Infantile hypotonia with psychomotor retardation and characteristic facies type 3(IHPRF3) (OMIM #616,900) is an autosomal recessive disorder caused by biallelic pathogenic variants of the TBCK gene, and to date, this disease was reported rather limitedly in number and all described cases were Caucasians. CASE PRESENTATION: This paper reported the clinical and genetic features of a Chinese patient with IHPRF3. The patient was a 15-month-old male with global developmental delay, profound hypotonia, and typical facial dysmorphic features including mildly coarse facial appearance, hypertelorism, tented upper lip, exaggerated Cupid's bow, macroglossia and arched eyebrows. Magnetic Resonance Imaging (MRI) analysis of the brain revealed slightly widened bilateral ventricles and subarachnoid space. On genetic analysis, the patient was homozygous for a novel TBCK variant c.247C > T(p.Arg83Ter). The parents were both carriers without any positive symptoms or signs. With an extremely low frequency (0.0000082) in Exome Aggregation Consortium, the variant has not been reported in any other databases or official literatures, and was diagnosed to be pathogenic according to the American College of Medical Genetics and Genomics(ACMG) standards and guidelines. Neurorehabilitation training did not work well and the long-term prognosis remained to be observed. CONCLUSIONS: This study reported the clinical and molecular features of the first non-Caucasian patient with IHPRF3 arising from a novel homozygous TBCK mutation, which provided a novel molecular marker for the definite diagnosis of IHPRF3 patients and for its genetic counseling and prenatal diagnosis in the affected families.
BACKGROUND: Infantile hypotonia with psychomotor retardation and characteristic facies type 3(IHPRF3) (OMIM #616,900) is an autosomal recessive disorder caused by biallelic pathogenic variants of the TBCK gene, and to date, this disease was reported rather limitedly in number and all described cases were Caucasians. CASE PRESENTATION: This paper reported the clinical and genetic features of a Chinese patient with IHPRF3. The patient was a 15-month-old male with global developmental delay, profound hypotonia, and typical facial dysmorphic features including mildly coarse facial appearance, hypertelorism, tented upper lip, exaggerated Cupid's bow, macroglossia and arched eyebrows. Magnetic Resonance Imaging (MRI) analysis of the brain revealed slightly widened bilateral ventricles and subarachnoid space. On genetic analysis, the patient was homozygous for a novel TBCK variant c.247C > T(p.Arg83Ter). The parents were both carriers without any positive symptoms or signs. With an extremely low frequency (0.0000082) in Exome Aggregation Consortium, the variant has not been reported in any other databases or official literatures, and was diagnosed to be pathogenic according to the American College of Medical Genetics and Genomics(ACMG) standards and guidelines. Neurorehabilitation training did not work well and the long-term prognosis remained to be observed. CONCLUSIONS: This study reported the clinical and molecular features of the first non-Caucasian patient with IHPRF3 arising from a novel homozygous TBCK mutation, which provided a novel molecular marker for the definite diagnosis of IHPRF3 patients and for its genetic counseling and prenatal diagnosis in the affected families.
Authors: Anas M Alazami; Nisha Patel; Hanan E Shamseldin; Shamsa Anazi; Mohammed S Al-Dosari; Fatema Alzahrani; Hadia Hijazi; Muneera Alshammari; Mohammed A Aldahmesh; Mustafa A Salih; Eissa Faqeih; Amal Alhashem; Fahad A Bashiri; Mohammed Al-Owain; Amal Y Kentab; Sameera Sogaty; Saeed Al Tala; Mohamad-Hani Temsah; Maha Tulbah; Rasha F Aljelaify; Saad A Alshahwan; Mohammed Zain Seidahmed; Adnan A Alhadid; Hesham Aldhalaan; Fatema AlQallaf; Wesam Kurdi; Majid Alfadhel; Zainab Babay; Mohammad Alsogheer; Namik Kaya; Zuhair N Al-Hassnan; Ghada M H Abdel-Salam; Nouriya Al-Sannaa; Fuad Al Mutairi; Heba Y El Khashab; Saeed Bohlega; Xiaofei Jia; Henry C Nguyen; Rakad Hammami; Nouran Adly; Jawahir Y Mohamed; Firdous Abdulwahab; Niema Ibrahim; Ewa A Naim; Banan Al-Younes; Brian F Meyer; Mais Hashem; Ranad Shaheen; Yong Xiong; Mohamed Abouelhoda; Abdulrahman A Aldeeri; Dorota M Monies; Fowzan S Alkuraya Journal: Cell Rep Date: 2014-12-31 Impact factor: 9.423
Authors: Sue Richards; Nazneen Aziz; Sherri Bale; David Bick; Soma Das; Julie Gastier-Foster; Wayne W Grody; Madhuri Hegde; Elaine Lyon; Elaine Spector; Karl Voelkerding; Heidi L Rehm Journal: Genet Med Date: 2015-03-05 Impact factor: 8.822