Department of Clinical Genetics, Centre for Human Genetics, Bangalore, Karnataka, India
Department of Paediatric Genetics, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India.
J Med Genet. 2023 Feb;60(2):204-211. doi: 10.1136/jmedgenet-2021-108098. Epub 2022 Apr 27.
Dyggve-Melchior-Clausen dysplasia (DMC) and Smith-McCort dysplasia (SMC types 1 and 2) are rare spondyloepimetaphyseal dysplasias with identical radiological findings. The presence of intellectual disability in DMC and normal intellect in SMC differentiates the two. DMC and SMC1 are allelic and caused by homozygous or compound heterozygous variants in . SMC2 is caused by variations in . Both and are important in intravesicular transport and function in the Golgi apparatus.
Detailed clinical phenotyping and skeletal radiography followed by molecular testing were performed in all affected individuals. Next-generation sequencing and Sanger sequencing were used to confirm and variants. Sanger sequencing of familial variants was done in all parents.
24 affected individuals from seven centres are described. 18 had DMC and 6 had SMC2. Parental consanguinity was present in 15 of 19 (79%). Height <3 SD and gait abnormalities were seen in 20 and 14 individuals, respectively. The characteristic radiological findings of lacy iliac crests and double-humped vertebral bodies were seen in 96% and 88% of the affected. Radiological findings became attenuated with age. 23 individuals harboured biallelic variants in either or . Fourteen different variants were identified, out of which 10 were novel. The most frequently occurring variants in this group were c.719 C>A (3), c.1488_1489del (2), c.1484dup (2) and c.1563+2T>C (2) in DYM and c.400C>T (2) and c.186del (2) in . The majority of these have not been reported previously.
This large cohort from India contributes to the increasing knowledge of clinical and molecular findings in these rare 'Golgipathies'.
Dyggve-Melchior-Clausen 发育不良（DMC）和 Smith-McCort 发育不良（SMC 类型 1 和 2）是罕见的脊椎-干骺端发育不良，具有相同的放射学发现。DMC 存在智力障碍，而 SMC 则智力正常，这将两者区分开来。DMC 和 SMC1 是等位基因，由 中的纯合或复合杂合变异引起。SMC2 是由 中的变异引起的。 和 对于囊泡内运输和高尔基体中的功能都很重要。
对所有受影响的个体进行详细的临床表型和骨骼放射摄影，然后进行分子检测。使用下一代测序和 Sanger 测序来确认 和 变体。对所有父母进行了家族变体的 Sanger 测序。
描述了来自七个中心的 24 名受影响的个体。18 名患有 DMC，6 名患有 SMC2。19 名中有 15 名（79%）存在父母近亲结婚。身高<3SD 和步态异常分别在 20 名和 14 名个体中可见。96%和 88%的受影响者有特征性的放射学发现，即花边髂嵴和双驼峰椎体。放射学发现随着年龄的增长而减弱。23 名个体在 或 中携带双等位基因变异。共鉴定出 14 种不同的变异，其中 10 种是新的。该组中最常见的变异是 c.719 C>A（3），c.1488_1489del（2），c.1484dup（2）和 c.1563+2T>C（2）在 DYM 中，c.400C>T（2）和 c.186del（2）在 中。这些变异大多数以前没有报道过。
来自印度的这个大型队列为这些罕见的“高尔基体病”的临床和分子发现提供了更多的知识。
