■下腰骶骨发育不良（MAD）综合征是一种罕见的遗传性疾病。几种孕激素综合征，包括下颌骨发育不良A型（MADA），下颌骨发育不良B型（MADB），哈钦森-吉尔福德早衰症（HGPS）和下颌骨发育不全，耳聋,和脂肪代谢障碍综合征（MDPL）以前已经报道过。最近报道了一种新的MAD孕激素综合征（MADaM）。到目前为止,在世界范围内已经报道了7例被诊断为分子诊断的MADaM。在中国人口中，从未报道过与MTX2变异相关的MAD病例.
■在患有该疾病的患者中确定并研究了临床症状和遗传分析。此外,我们分析并比较了全球报告的7例MADaM病例,并总结了迄今为止在中国人群中报告的早衰综合征.
■本研究报告了一例MTX2基因中一个新的纯合突变c.378+1G>A，以前在文献中没有报道过。出现早期发作和严重症状以及出生后不久的患者被发现具有生长迟缓。除了早衰的特征，骨骼畸形，先前报道的全身性脂肪营养不良，和其他多系统参与，例如肝脾，肾,和心血管系统，据报道，该病例还合并了低球蛋白血症。此后，她因感染多次入院。在先前报告的22种早衰综合征中，16/22是由LMNA基因突变引起的MADA或HGPS，纯合c.1579C>T（p。R527C）突变可能是中国人群MAD的热点突变。MAD和HGPS主要存在于有皮肤异常或脱发的婴儿期，MDPL主要表现在学龄期，以生长迟缓为第一表现，并且通常在几十年后与内分泌代谢紊乱相结合。
■这是中国人群中报道的第一例由MTX2基因突变引起的MAD综合征。MTX2基因c.378+1G>纯合突变以前没有报道，该患者的报道扩大了MTX2突变的范围。此外,我们总结了中国早衰综合征患者的基因型和临床特征。
UNASSIGNED: Mandibuloacral dysplasia (MAD) syndrome is a rare genetic disease. Several progeroid syndromes including mandibuloacral dysplasia type A (MADA), mandibuloacral dysplasia type B(MADB), Hutchinson-Gilford progeria (HGPS) and mandibular hypoplasia, deafness, and lipodystrophy syndrome (MDPL) have been reported previously. A novel MAD progeroid syndrome (MADaM) has recently been reported. So far, 7 cases of MADaM diagnosed with molecular diagnostics have been reported in worldwide. In the Chinese population, cases of MAD associated with the MTX2 variant have never been reported.
UNASSIGNED: The clinical symptoms and the genetic analysis were identified and investigated in patients presented with the disease. In addition, we analyzed and compared 7 MADaM cases reported worldwide and summarized the progeroid syndromes reported in the Chinese population to date.
UNASSIGNED: The present study
reports a
case of a novel homozygous mutation c.378 + 1G > A in the MTX2 gene, which has not been previously reported in the literature. Patients present with early onset and severe symptoms and soon after birth are found to have growth retardation. In addition to the progeroid features, skeletal deformities, generalized lipodystrophy reported previously, and other multisystem involvement, e.g. hepatosplenic, renal, and cardiovascular system, this
case was also reported to have combined hypogammaglobulinemia. She has since been admitted to the hospital several times for infections. Among 22 previously reported progeroid syndromes, 16/22 were MADA or HGPS caused by LMNA gene mutations, and the homozygous c.1579C > T (p.R527C) mutation may be a hot spot mutation for MAD in the Chinese population. MAD and HGPS mostly present in infancy with skin abnormalities or alopecia, MDPL mostly presents in school age with growth retardation as the first manifestation, and is often combined with an endocrine metabolism disorder after several decades.
UNASSIGNED: This is the first
case of MAD syndrome caused by mutations in MTX2 gene reported in the Chinese population. MTX2 gene c.378 + 1G > A homozygous mutation has not been previously reported and the report of this patient expands the spectrum of MTX2 mutations. In addition, we summarized the genotypes and clinical characteristics of patients with progeroid syndromes in China.
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