Ullah Asmat, Ali Raja Hussain, Majeed Ayesha Isani, Liaqat Khurram, Shah Pashmina Wiqar, Khan Bushra, Bilal Muhammad, Umair Muhammad, Ahmad Wasim
Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, 02115, USA.
Eur J Med Genet. 2019 Apr;62(4):278-281. doi: 10.1016/j.ejmg.2018.08.005. Epub 2018 Aug 11.
Mesoaxial syndactyly is characterized by fusion of the central digits. The disorder segregates in autosomal recessive pattern and mapped on human chromosome 17p13.3. Homozygous missense mutations in the BHLHA9 have been reported to cause mesoaxial synostotic syndactyly with phalangeal reduction (MSSD). In the present study, we have investigated a family segregating mesoaxial synostotic syndactyly with phalangeal reduction (MSSD) in autosomal recessive manner. Genotyping using microsatellite markers followed by Sanger sequencing revealed a homozygous deletion and insertion mutation (NM_001164405: c.252_270delinsGCA; p.(Phe85Glufs*108)) in the BHLHA9 gene in affected individuals of the family. This study reports the first frameshift mutation in the BHLHA9 causing mesoaxial synostotic syndactyly and phalangeal reduction.
中轴型并指畸形的特征是中间手指融合。该疾病以常染色体隐性模式遗传，定位于人类染色体17p13.3。据报道，BHLHA9基因中的纯合错义突变会导致伴有指骨发育不全的中轴型并指骨联合畸形（MSSD）。在本研究中，我们调查了一个以常染色体隐性方式遗传伴有指骨发育不全的中轴型并指骨联合畸形（MSSD）的家系。使用微卫星标记进行基因分型，随后进行桑格测序，结果显示该家系中受影响个体的BHLHA9基因存在纯合缺失和插入突变（NM_001164405: c.252_270delinsGCA; p.(Phe85Glufs*108)）。本研究报道了BHLHA9基因中首个导致中轴型并指骨联合畸形和指骨发育不全的移码突变。
